STAMPEDE: CRF Completion Guidelines

Transcription

1 : CRF Completion Guidelines V2.0

2 Randomisation

3 Eligibility checklist Administrative checklist to ensure all screening procedures have been completed Not required to be sent to MRC CTU

4 Randomisation Complete Randomisation CRF Call the MRC CTU Randomisation line Monday to Friday Excluding public holidays or dates when notice has been given by the CTU. Tel: +44 (0) Complete Randomisation section of Randomisation CRF with Patient ID, treatment allocation and date of randomisation

5 After Randomisation On the date of randomisation: MRC CTU will send an confirming the patient s trial ID and treatment allocation to FPOCs and pharmacists on the date of randomisation Shortly after randomisation: MRC CTU will send 2 copies of the Randomisation Confirmation (transcript of Randomisation call) Treatment and Follow-Up Schedule

6 CRF Training

7 Requirement for Source Data Reminder: it is important for research data that information provided on CRFs must be verifiable in the source documentation at site. Examples of source documents includes but not limited to: Clinic notes medical records laboratory reports medication records Prescriptions research notes pathology reports radiology reports

8 Baseline CRFs Case Report Form Randomisation Baseline Cardiovascular Assessment Bone Density Risk Factor Timing and Assessment of CRF At randomisation At randomisation At randomisation At randomisation

9 Treatment CRFs Case Report Form SOC Docetaxel Treatment SOC Hormone Therapy Log Abiraterone and Enzalutamide Treatment Log (Arm G and J only) Timing and Assessment of CRF To be completed for all patients 20 weeks after randomisation. To be completed every time there is a change in SOC hormone therapy to report (including when Arm L patients switch to SOC HT preprogression). To be sent in with the corresponding Follow-Up CRF. To be completed when treatment is first started and subsequently every time there is a dose change, treatment pause and re-start. To be sent in with the corresponding Follow-Up CRF.

10 Treatment CRFs Case Report Form Metformin Treatment Log (Arm K only) Transdermal Oestradiol Treatment Log (Arm L only) Transdermal Oestradiol Hormone Results Log (Arm L only) Timing and Assessment of CRF To be completed when treatment is first started and subsequently every time there is a dose change, treatment pause and re-start. To be sent in with the corresponding Follow-Up CRF. To be completed when treatment is first started and subsequently every time there is a dose change, treatment pause and re-start. To be sent in with the corresponding Follow-Up CRF. To be completed with scheduled and ad-hoc hormone test results

11 Treatment CRFs Case Report Form RT Detail RT Acute Toxicity End of Research Treatment Timing and Assessment of CRF To be completed for all patients: Upon completion of SOC RT If planned RT is no longer to be given (at 10 months after randomisation) Arm H patients when research RT completed Arm A patients with newly-diagnosed M1 disease at 3 months to confirm RT was not given For all patients who receive primary RT. To be completed when (each) allocated research treatment is permanently stopped or in the event that allocated research treatment is never started (in each case a reason for stopping/never starting should be provided).

12 Assessments Case Report Form Follow-Up Progression Log Timing and Assessment of CRF To be completed every 6 weeks for 6 months, then every 12 weeks until 2 years, then every 6 months until 5 years and annually thereafter. To be completed at the occurrence of each progression event (PSA, local, nodal, distant metastases) and for each method of detection (clinical/symptomatic and objective/radiological). Skeletal-related events confirmed as progression should also be reported here.

13 Assessments Case Report Form Additional Treatment Log Serious Adverse Event Death Timing and Assessment of CRF To be completed each time a patient who has progressed starts or completes any additional treatment for progression. To be completed following any Serious Adverse Event At Death Patient Transfer Confirmation Form To be completed when a patient is transferred to a different hospital for the administration of trial treatment and follow-up Co-enrolment To be completed when a patient is co-enrolled in any other clinical trial.

14 Translational Sub-Studies Case Report Form Saliva Pathology Blood (Participating Arm A, J, K and L patients only) Tissue Samples Timing and Assessment of CRF To be completed when saliva sample has been taken and sent to Sponsor's designated laboratory. To be completed at expected timepoints for blood samples To be completed with each shipment of tissue samples sent to designated biobank.

15 General principles Queries relating to an event that occurred prior to 20 th June 2017 must be amended or updated on old CRFs

16 General principles Use most up to date version of the CRF CRFs should always be signed and dated CRF without a signature or date of completion cannot be accepted Use unit measurement specified on CRF (i.e. PSA in ng/ml) If lab provides measurements in different units, please use a converter (available on the internet) to find the correct value in required units Changes should be initialled and dated CRFs should be completed by trained and delegated staff Answer Not Known / NK or Not Done ND where needed Missing data will be queried

17 General principles CRFs to be completed using Key provided Tick boxes

18 General principles Common abbreviations can be used. If in doubt please write in full. lt or L Left rt or R Right pt Patient - Increase - Decrease > - more than < - less than PRN take (medication) when needed Tx treatment Suggestions for improvement are welcome!

19 Randomisation Form: Page 1 Only to be completed on Randomisation CRF Please refer to eligibility checklist or Protocol section prior to answering Yes. The checklist does not need to be sent in. Please note Pre-hormone PSA should ideally be within 6 months prior to randomisation

20 Randomisation Form: Page 2 At least one of these questions must be answered 1=Yes for the patient to be eligible for Both conditions should be met for those patients potentially randomising to the metformin comparison

21 Randomisation Form: Page 2 For relapsing patients both Q20 and Q21 should be answered. Please note, any prior course of HT for localised disease must be completed 12 months prior to randomisation and shouldn t be longer than 12 months Medications of interest confirmed at randomisation. Long-term therapy is defined as treatment planned for 6 months or more.

22 Randomisation Form: Page 3 Please note Guidance on timelines for starting hormone therapy Please note

23 Randomisation Form: Page 3 Please ensure timelines for starting docetaxel are adhered to. Date of randomisation and start date of HT both need to be considered.

24 Randomisation Form: Page 4 Please note New questions on version 15.0 Randomisation form

25 Randomisation Form: Page 4 Details regarding tissue samples to be collected at randomisation, this information will contribute towards sub-studies. These questions are not asked during the Randomisation call, but should be completed before randomisation CRF is sent to the CTU.

26 Baseline Form Patient must have had either a Bone Scan or Whole Body MRI. If a PET has been performed, the CT component can be used instead of a bone scan. Provide testosterone levels prior to hormone therapy, if available Blood tests should ideally be taken within 8 weeks prior to randomisation. However, for patients receiving SOC docetaxel prior to Randomisation, pre-chemo haematology results taken more than 8 weeks prior will be accepted. Please note

27 Cardiovascular Form Diabetic patients will only be eligible for under protocol v16.0 (Arm L). Please note for all patients on Arm K, this question should be answered 0 = No. Please note HDL/LDL cholesterol values should be lower than total cholesterol

28 Bone Density Risk Factor Form This CRF should be completed for all patients prior to randomisation. If not done at randomisation, please send in a form stating Missed in error Complete the signature strip at the bottom of all the baseline forms (page 3 of 3) (Baseline, Cardio, and Bone Density) to confirm all details are correct. Please also send through a copy of the Patients consent form with all Baseline forms

29 Follow-Up Form Please note there is no longer a post-progression form for CRFs from Protocol version 15 onwards. If the date of follow-up visit you are completing occurred before the 5 th September 2016, please complete: Follow-Up Form PR08 Form 7, V12 or Follow-Up Form (post-progression) PR08 Form 7A, V11. If the date of follow-up visit you are completing occurred between the 5 th September 2016 and 19 th June 2017, please complete: Follow-Up Form PR08 Form 7, V13. If the date of follow-up visit you are completing occurred on/after the 20 th June 2017, please complete: Follow-Up Form PR08 Form 7, V14. Please note that the Toxicity Form 7E may not need to be completed for patients after progression. Please refer to on-form guidance.

30 Follow-Up Form: Page 1 If no contact with patient, please report as missed visit e.g. unable to contact patient by phone. Please note Q 1, 2 & 3 should be answered in all circumstances Please ensure this is answered if the visit has been missed and please consider using other sources of information to determine last date known to be alive e.g. clinic notes, liaising with GP. Please give information for all long-term medications of interest for all patients using Yes/No Providing the lowest and highest PSA values in the last follow-up period will enable us to better calculate the progression value and also see when it is breached. If only one PSA value is available it should be reported under Lowest PSA.

31 Follow-Up Form: Page 1 Please read definition of the categories of progression before answering 1=Yes 1=Yes should only be entered if the patient has progressed since last trial follow up If Q answered 1 = yes, check if updated progression log is required. Please note progression of each type only needs to reported once, the first time it occurs. Biochemical progression Once you have reported 1 = yes for biochemical progression during a particular follow-up period, please ensure you answer 2 = first instance already reported on subsequent follow-up forms. Objective and Symptomatic progression Objective and Symptomatic progression should only be answered 1=Yes if the patient has experienced either progression type (local, nodal and distant metastases) within that FU period. E.g. if you have reported 1=yes for objective progression on the week 36 follow-up form, do not report it again on the week 48, and subsequent follow-up forms. Please note that we expect the first clinical and objective instance of local, nodal and distant metastases progression to be reported on a Progression log.

32 Follow-Up Form: Page 2 Please answer 1=Yes only if patient had any non-trial inpatient/outpatient/gp visits relating to prostate cancer Contact the trial team if you are unsure if an event constitutes as an SAE Please note RTOG includes RT given for SOC, trial treatment (Arm H) or for progression purposes If Q21 answered 1=Yes, all toxicities should be marked Please use the key provided to report details of any surgical intervention which may have been carried out since the last follow up.

33 Follow-Up Form: Page 3 Answer 1 = yes here if, there has been a change relating to SOC HT only. AAs prescribed for progression should be reported on Additional Trt Log. Please clarify whether patient experiences any of the events listed (Q24,25,26) and whether the event was later confirmed as progression Where you have answered 1=yes, please attach the corresponding form with the FU To be completed for Arm A patients randomised on/after 5 th September and ALL arm K and arm L patients. Only to be completed for Arm A patients randomised on/after 5 th September and ALL arm K patients. Details for metabolic profile need to be completed at specific time-points in accordance with the protocol.

34 Follow-Up Form: Page 4 Please answer 1=Yes if Metformin is started for the first time, dose changed, treatment pause for more than 7 days or treatment is restarted since last trial follow-up and complete corresponding Metformin Log with details. Please note for Qs 34, 36, 40 & 42, only answer 2 = N/A stopped permanently if no trial treatment has been administered during this FU period. Please note specific monitoring checks should be performed for patients on Arms K, G and J (as detailed in the protocol). If monitoring checks are not performed please contact CTU. For Arm G/ J patients if trial treatment has started, dose changed, paused or restarted answer 1=Yes and complete corresponding trial treatment log and complete Qs on this form.

35 Follow-Up Form: Page 4 Please answer 1=Yes if transdermal oestradiol is started for the first time, dose changed, or type of patch changed since last trial followup and complete corresponding Transdermal Oestradiol Log with details.

36 Follow-Up Form: Page 5 If patient does not report any toxicities, answer Q 44 as 0 = No. In this case please sign and send the follow-up CRF and toxicity form does not need to be sent in. If patient experienced toxicity within this follow up period, answer 1 = yes and complete toxicity form. We are interested in all toxicities whilst patient is on 1 st line treatment. Therefore please report toxicities until the FU period AFTER 2 nd line treatment is started and 1 st line treatment has permanently stopped (n/a for arm A). Please answer 2 =n/a going forward once the above has occurred.

37 Toxicity Form: Page 1 The toxicity form must be sent with either: Follow-up Form End of Research Treatment Treatment Log or Form Toxicities relating to treatment action should only be reported in the event an End of Research Treatment or Treatment Log is completed. The Toxicity Form will be available on the website with and without the Follow-up section attached. Please note if reason for stopping research treatment is 2=Excessive toxicity then toxicity form with the same stopping date will be chased if not previously submitted. Dates provided here should match the dates provided on corresponding form. i.e. if date reported for Followup is 01/12/2016 then date on toxicity form should be 01/12/2016

38 Toxicity Form: Page 1 Please note CTCAE v4.0 should be referred to when reporting and grading toxicities Where boxes are unavailable the grading does not apply i.e. for Abdominal pain maximum toxicity is grade 3 Please either tick or cross on the grading which is applicable to the toxicity. Where a toxicity did not occur please mark N/A. If no toxicities within the category occurred please tick Mark if none

39 Toxicity Form: Page 2 Please only report Other disorder toxicities if toxicity is clinically relevant and listed in CTCAE 4.0. Exact lab measurements do not need to be provided. Please just confirm if value was high or low. Please note if you have reported toxicities on the toxicity form, this needs to be attached to the relevant form and if toxicity form is NOT signed and dated we will not be able to accept the forms.

40 How to complete the Toxicity Form Responses to be queried Accepted Responses If patient experiences only one toxicity under a category, please mark all other toxicities listed under the category as N/A. Missing answers will be queried. A toxicity (insomnia) was incorrectly graded, however the site crossed out the incorrect grade (G1) then circled the correct grade (G3), and initialled and dated the updated information. In this example, the site has marked that the patient has no nervous system toxicities but also marked dizziness as Grade 1. This would be queried asking whether the patient has experienced the toxicity or not. No toxicity was experienced and so the site has correctly marked the mark if none box.

41 How to complete the Toxicity Form Responses to be queried Accepted Responses Here the toxicity reported for blurred vision is unclear. Only one grade should be marked clearly. Responses which are unclear/ambiguous will be queried. Both examples above are acceptable ways of reporting toxicities.

42 Treatment Logs Each time an update is made to a treatment in any form listed above, this should be recorded on the correct row. Each update should be initialled and dated clearly by a delegated member of staff. For every update made to the log, a copy should be made and sent to the unit. Send in all pages, if multiple used. We do not require sites to complete details of treatment on the logs retrospectively (i.e. if data has already been reported on a previously used form).

43 Post-randomisation AA Patient is taking Anti-Androgens For progression? Additional Treatment Form Yes No For flare? No Yes Are they on Arm L? SOC Hormone Therapy Log Yes Follow-Up Form No Do not report

44 Post-randomisation LHRH Patient is taking LHRH For progression? Yes No Additional Treatment Form SOC Hormone Therapy Log

45 SOC Hormone Therapy Log This form should capture changes to LHRH, AA or Orchidectomy only Row 1 should be populated with details of the starting primary long-term hormone therapy. For Arm L patients who switched treatment from transdermal oestradiol to SOC HT after randomisation, please report here and populate row 1 with details for first time patient switched to SOC HT. Please note here, there are some circumstances in which reporting changes to LHRH or AA do not need to be recorded (e.g. do not report AA for flare). If 99= Other, chosen as option for any question please provide details. Where applicable use the keys provided to complete the text boxes. For example key A correlates to Type of action. All updates should be signed and dated. Updates unsigned or undated cannot be entered and these forms will be queried and chased via .

46 Abi Enza Treatment Log This log is to be completed for those patients on Arm G and J only. If 99= Other, chosen as option for any question please provide details. Where applicable use the keys provided to complete the text boxes. For example key A correlates to Type of action. If patient has permanently stopped treatment, please report this on the relevant end of treatment form. All updates should be signed and dated. Updates unsigned or undated cannot be entered and these forms will be queried and chased via . Where treatment was reduced or paused due to toxicity, please ensure corresponding Toxicity Form is attached.

47 Metformin Treatment Log This log is to be completed for those patients on Arm K only. Where toxicity is chosen or treatment is permanently stopped or never started please ensure the additional action is taken. All updates should be signed and dated. Updates unsigned or undated cannot be entered and will be sent back. Trial team should be contacted prior to 99=Other being chosen for Metformin dose

48 Transdermal Oestradiol Treatment Log This log is to be completed for those patients on Arm L only. Record the first dose, last dose, and any dose changes between. Trial team should be contacted prior to 99=Other being chosen for transdermal oestradiol dose All updates should be signed and dated. Updates unsigned or undated cannot be entered and will be sent back.

49 Transdermal Oestradiol Hormone Results Log This log is to be completed for those patients on Arm L only. Please complete this form for patients receiving transdermal oestradiol every time there are testosterone and/or oestradiol results (scheduled and additional). Out of range blood tests: If the patients oestradiol level is <300pmol/L or >2000pmol/L and/or testosterone >1.7nmol/L please contact a member of the Trial team. All updates should be signed and dated. Updates unsigned or undated cannot be entered and will be sent back.

50 Progression defines disease progression as: Biochemical failure o The date that the trial PSA progression value was breached Local, lymph node and metastatic failure o Date of first clinical/symptomatic progression e.g. Reported date that bone pain worsened o Date of first objective/radiological progression e.g. Date bone scan confirmed progression/and or new bone mets Skeletal-related event confirmed as progression e.g. pathological fracture confirmed as due to progression of bone mets For further details see Protocol Section 7

51 PSA PSA What does NOT constitute progression? The addition of anti-androgens may or may not constitute progression Anti-androgens e.g. bicalutamide can be added as a change in long-term hormone therapy or as a treatment for progression LHRHa LHRHa Antiandrogens Anti-androgens PSA progression value Scenario 1: Change in long-term HT Anti-androgens added due to poor PSA response on LHRHa alone Report as: Change in long-term hormone therapy to dual-androgen blockade Scenario 2: Anti-androgens as a treatment for progression Anti-androgens added due to rising PSA Report as: progression

52 What DOES constitute progression? There are three categories of progression in : 1. Biochemical (PSA) 2. Objective detected radiologically 3. Symptomatic detected clinically Objective/radiological and symptomatic/clinical progression can both be further broken down into four types of progression: Local progression Lymph node progression Distant metastatic progression Skeletal related events (SREs)

53 What DOES constitute progression? Does each type need to be reported? Yes, progression of each type (local, lymph nodal, distant mets and SREs) needs to be reported the first time it occurs For example: Date of clinical local progression i.e. symptoms worsened Date of radiological local progression i.e. MRI/CT confirmed Date of bone metastases clinically suspected Date new bone metastases confirmed on bone scan If we receive more than one progression log with two different dates reported for the same type of progression, this will be queried

54 Definition: Biochemical Progression What is the PSA progression value? A threshold PSA value for defining biochemical progression Calculated using PSA measurements taken prior to starting ADT and weeks 6, 12, 18 and 24 It is patient specific and calculated based on all reported PSA values up to 24 weeks post randomisation PSA progression is defined as the date the PSA value first reaches the PSA progression value Confirmatory PSA test should be taken within 12 weeks of first raised PSA.

55 PSA PSA PSA Definition: Biochemical Progression How is the PSA progression value calculated? It is a calculated value relative to the pre-treatment PSA and the lowest PSA recorded in the first 24 weeks on trial (PSA nadir) Scenario 1: Immediate treatment failure PSA nadir >4 and >50% pre-treatment PSA Scenario 2: PSA progression value >50% above PSA nadir PSA nadir >4 and <50% pre-treatment PSA Scenario 3: PSA progression value >4 OR >50% above PSA nadir (whichever is higher) PSA nadir 4 Note: It is not necessary to know which scenario your patient falls under, this is defined by the Progression Calculator Scenario 1 Scenario 2 Scenario 3 4 PSA nadir is >4 and >50% the pre-treatment = treatment failure 9 6 PSA PSA nadir>4 Progression value value = 50% 50% above nadir nadir 4 PSA nadir 4 Progression value at least 50% above nadir and >4 Time Time Time

56 PSA Progression Value Calculator How can you calculate the progression value for each patient? Follow the hyperlink to the website

57 PSA Progression Value Calculator Progression category C Report progression where PSA value is 4.0ng/ml

58 PSA Progression Value Calculator Progression category B Report progression where PSA value is 8.1ng/ml

59 PSA Progression Value Calculator PSA outside 24 weeks Week 24 value: 05/05/ ng/ml has not been used Report progression where PSA value is 8.6ng/ml

60 PSA Progression Value Calculator Progression category A If the patient is determined to be PSA failure category A, follow the directions on the calculator, reporting the lowest PSA value as progression.

61 How to report: biochemical progression When is a confirmatory PSA value required? When reporting isolated biochemical progression Why? Because PSA levels can rise for other reasons therefore please confirm progression if possible Timing of test: Ensure confirmatory test is carried out within 1-12 weeks of initial test in which progression value was reached How is it confirmed? Biochemical progression is confirmed if the second value is around the same or higher than the first raised PSA i.e. trend confirmed Which date should be reported? The PSA value which first breached the patientspecific PSA progression value

62 How to report: biochemical progression When is a testosterone level required? Only when reporting biochemical progression occurring whilst on hormone therapy. This is to confirm a castrate level of testosterone (<50ng/dl or <1.7nmol/L) Which PSA value should be reported if a second line treatment is started to treat biochemical progression? The date of the first PSA test that reached the progression value should be given If treatment is given specifically for biochemical failure but before progression value has been reached provide the closest PSA value prior to treatment starting Every time a new progression is reported a delegated staff member should clearly initial and date in the text box below.

63 Definition: Objective and Symptomatic How are the other types of progression defined and detected? 2. Objective progression (Radiological progression) Radiological evidence in the form of scans demonstrating local, lymph nodal, distant metastases and/or a Skeletal Related Event (SRE) SREs are defined as: Pathological fracture Spinal cord compression Requirement for RT to bone (e.g. for pain or impending fracture) Requirement for surgery (e.g. for prevention or management of fracture) 3. Symptomatic progression (Clinical progression) Appearance or worsening of cancer-related symptoms Suggestive of local (e.g. prostate bed), lymph node (e.g. pelvic) or distant metastatic (e.g. non-pelvic lymph node or bone) disease progression

64 How to report: objective and symptomatic 1. Update the Progression Log There should be one progression log for each patient. Each update should be made on the same Log and copy of the updated log should be sent to the CTU. Provide the date of the first reported clinical/objective progression. Confirm any new site(s) of distant metastases (not those reported at randomisation) the first time they occurred (only needs to be answered if question 4a and/or 4b has been answered). Every time a new progression is reported a delegated staff member should clearly initial and date in the text box below. Provide the earliest reported date that each of the skeletal related events listed occurred Please note: **The date of progression is defined as the earliest date of detection e.g. If clinical progression is detected and subsequently confirmed with imaging, provide the date of clinical progression**

65 Additional Treatment Log All treatments for progression are to be recorded on the Additional Treatment Log. This form should be attached to Progression Log if treatment given Please note if patient is enrolled into another clinical trial postprogression please use the BLIND code if treatment unknown Initial and date after reporting starting and stopping of treatments Where applicable please provide additional information for treatments prescribed i.e. if Other Bisphosphonate (BIS) chosen please provide name

66 Radiotherapy Detail Form Please note this form is to be completed for those patients who are receiving radical RT to the prostate as part of SOC or Arm H allocation Please note the date of first fraction given should not be before randomisation. If palliative RT given before randomisation this should not be reported here. Please provide a reason if the dose to pelvis is higher than 55Gy in 37 fractions. If either option 2, 4 or 5 is chosen as a reason for stopping. Please complete corresponding form and attach to the CRF.

67 Radiotherapy Acute Toxicity Form See guidance for when to complete form Toxicities can be completed on alternate weeks, as long as all missing weeks are completed retrospectively. Toxicities can also be recorded via telephone follow-up with the patient.

68 Standard-Of-Care Docetaxel Form To be completed for all patients who were: -Randomised from 17-Dec-2015 (Protocol V14.0) -Received SOC docetaxel before 17-Dec-2015 If SOC Docetaxel not planned (& not given) -Complete Q1 -Sign, date and return If either option 1 or 2 is chosen as a reason for giving less than 6 cycles. Please complete corresponding form and attach to the CRF.

69 End of Research Treatment Form Protocol treatment complete should not be selected as a response if patient falls under any of these categories If reporting the permanent stopping of any other research treatments (i.e. Zoledronic acid, docetaxel, celecoxib), please find the appropriate version on the website If any of these options are chosen please ensure corresponding CRF is completed

70 Death Form This CRF should be completed as soon as possible after a patient has died. Please note to ensure that any outstanding forms are entered and queries closed, we will be sending sites an FSR and DCF report after a Death form is received If primary or underlying cause of death is thought to be prostate cancer (related to disease or treatment) please complete Q2 with code 01=Prostate cancer The death certificate should be referred to when completing this form. Attach an anonymised copy of the death certificate if available For Q 9, report as an SAE (1=yes), if Q7 answered yes and/or Q8 answered 1, 2 or 3

71 Co-Enrolment Form Complete either section A or B, depending on which section you hold complete details for. Patients should not be co-enrolled into any other clinical trials involving interventional treatment until they have progressed and stopped trial treatment. If treatment is allocated on new study, please complete Additional Treatment Log with details. Delegated staff member should initial in this text box to confirm that co-enrolment does not impede participation in.

72 Saliva Pathology Form Saliva sample can be taken at any point in the trial from patients (all arms) who have joined the trial since November Please only complete as sample not taken if it will not be taken in the future, rather than having been missed on one occasion. Send one copy of the form with the saliva sample to the lab address Send a copy of the form to MRC CTU

73 Blood Form Please complete even if sample has been missed complete questions 2-5 Please complete for arm A, J, K or L patients who have consented to collection of blood for additional research Registration sample should only be ticked for patients in the Biomarker- Screening pilot study Tick the expected timepoint for the patient s metastatic status

74 Tissue Sample Form Please complete a separate form each time you send a shipment of samples. Send one copy of the CRF with the tissue blocks and slides and another copy to the MRC CTU

75 Early Cessation of Trial Follow-Up Some patients might be unable to continue trial assessments and FU Longer-term follow up information, even if just limited to whether the patient is still known to be alive, is very important in ensuring that the efforts on the part of the patient and research team translate into meaningful results We ask that you consider the following questions: Is the patient still being seen at your centre? Is the patient still being followed-up at the hospital e.g. in other department? Is the patient still registered with a GP? Has the patient transferred to another site participating in? If the answer to any of the above is yes the patient does not need to formally end their trial participation as it may still be possible to obtain follow-up data through other means.

76 Early Cessation of Trial Follow-Up Please consider the following options as a way of reducing the burden of follow-up: The patient has been provided with the option of continuing follow-up via telephone. The patient is aware that it is possible to continue providing follow-up data from their routine clinic/doctors notes. In both of the above instances, when completing the FU CRF please provide the date the patient was last known to be alive (Q4) and provide all other available data, clearly identifying those items for which the information was unavailable. Should the patient wish to terminate protocol specified follow-up schedule (via telephone consultation or via clinical notes, GP or national registries), the site is required to outline the patient s wishes in writing with a detailed description of the discussion with the patient. This should be ed to the Trial Team (mrcctu.stampede@ucl.ac.uk), clearly indicating the patient s ID, and filed with the patient s CRFs and all documentation relevant to their participation in the trial.

77 Quality of Life Form If the patient has consented to participate in the Quality of Life study, a copy of the form should be completed at baseline and alongside every follow-up visit. Please ensure the date of assessment is written on the QOL. Is QOL data collected post-progression? Arm A: QOL forms should be completed up until second line treatment has been added. All other research arms: QOL forms should be completed up until second line treatment has been added and first-line treatment has been permanently stopped

78 Form status reports and DCFs Unfortunately it is not possible for us to send individual files for all transferred patients on. If there are outstanding forms or queries relating to the period prior to a patient s transfer to your site Contact the randomising centre for this information If you have received a DCF and form status for a patient who has transferred to another site Contact with a copy of the Patient Transfer Form

79 Form status reports Please send any outstanding forms, including confirmation of any missed visits. If a form has been sent previously, please check that it is the correct version and that it has been signed and dated before sending again. Follow-up form may have been entered under a different week number if appropriate. Please cross check follow-up date of assessment with form dates stated in the report. Where a patient has ended their trial participation but has given permission for the data and information on their health to be collected via clinical notes & national registries, forms will be chased. Any information on the follow-up status, however minimal would be helpful.

80 Form status reports Transferred Patients will have their randomising centre listed as the site on form status report so please don t be alarmed. If you are unsure then please contact the team for clarification.

81 Data Clarification Forms (DCFs) Please respond in the space provided on the form and amend CRFs where necessary. The amended CRFs do not need to be sent back if query response is clearly answered on the data clarification form. Please be as descriptive as possible in the query response. If you have answered the query before, please complete it again or attach a copy of the previously completed DCF. If sending amended pages, please ensure that it is clear which form it belongs to i.e. date of assessment at the top.

82 DCFs Bisphosphonate Forms Please ignore the number in brackets in Form Name for all bisphosphonate forms, as this does not correspond to the cycle number. Please use the date of form for reference here.

83 DCFs RT Acute Toxicity Form The bladder and bowel grades on the RT acute toxicity form are named based on the number of boxes on the form and not the week number. Please note that [9] refers to week 10, [10] refers to week 12 and [11] refers to week 18.

84 Data Clarification Forms (DCFs) Please be as descriptive as possible in the query response.

85 Data Clarification Forms (DCFs) Please be as descriptive as possible in the query response.

86 Data Clarification Forms (DCFs) If you have answered the query before, please complete it again or attach a copy of the previously completed DCF.

87 Data Clarification Forms (DCFs) If you have answered the query before, please complete it again or attach a copy of the previously completed DCF.

88 Data Clarification Forms (DCFs) If you have answered the query before, please complete it again or attach a copy of the previously completed DCF.

89 Data Clarification Forms (DCFs) If you have answered the query before, please complete it again or attach a copy of the previously completed DCF.

90 Data Clarification Forms (DCFs) Please respond in the space provided on the form and amend CRFs where necessary. Please be as descriptive as possible in the query response.

91 Patient transfer form This CRF should be completed when a patient transfers his care to another site. This section should be completed by the site where the patient is currently being seen. This section should be completed by the site where the patient wishes to transfer to.

92 Patient transfer form A fully completed form must be returned to the CTU (mrcctu.stampede@ucl.ac.uk or fax ) Any outstanding CRFs or queries should be sent to the CTU. If last chase was more than 3 months prior, an updated DCF and form status report should be requested. Photocopies of the following documents may then be sent to the receiving site to complete the transfer (copies must be also retained at the original site) Consent form Completed CRFs Any documentation relating to the patient s participation in (patient names must be removed from any documentation) The patient should be re-consented on the latest version of the consent form and patient information sheets, at the next available follow-up at the receiving hospital.

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