AstraZeneca Hepatocellular Cancer Feasibility - Market Company Input

Transcription

1 AstraZeneca Hepatocellular Cancer Feasibility - Market Company Input DrugDev is working with AstraZeneca to gather your feedback for allocation consideration for the upcoming A Phase III Randomized, Open-label, Multi-center, Global Study of Durvalumab and Tremelimumab Administered as a Monotherapy or in Combination versus Standard of Care in First-Line Treatment of Patients with Advanced Hepatocellular Carcinoma (D419CC00002). For a copy of protocol synopsis please click here. If you wish to access the full questionnaire in pdf format before entering your answers online please click here. Please note this survey will close on Monday, 24th October 2016 at 12 pm (BST). Thank you and we look forward to receiving the completed survey with your comments. Country Contact Questions 1) Country Contact completing feasibility questionnaire (person to reach out to should follow-up questions be necessary)

2 Name: Country: 2) Who is the country specific operations person that the global project team should engage for start-up activities? Name: Country: Patient Population Questions 3) Is this study acceptable from a medical, ethical and regulatory perspective in your country?

3 If no, please specify any difficulties and provide recommended changes. 4) This study plans to enroll advanced Hepatocellular Carcinoma (HCC) Stage IV patients, with no prior systemic therapy, irrespective of viral status (excluding Fibrolamellar HCC, Sarcomatoid HCC or mixed Cholangiocarcinoma and HCC). The patients should not be amenable to locoregional therapy or should have disease progression after surgical or locoregional therapy for advanced HCC. Can this population be recruited in your country?

4 Are there any particular challenges that will make it difficult to recruit this population? If yes, please specify: 5) To help us better understand the patient population in your region, what % of advanced HCC patients fall in each of the following categories: HBV positive? HCV positive? Un-infected?

5 6) In your region, for first line Sorafenib regimen in HCC, what is the observed duration in months for: Overall Survival (OS)?: Time to Progression (TTP)?: Progression Free Survival (PFS)?: Overall Response Rate (ORR)?: 7) In your region, is Sorafenib the approved standard (or preferred) first-line treatment of patients with advanced or metastatic HCC who are refractory or not amenable to loco-regional therapy? 8) Other than sorafenib, what systemic therapies are used in first line treatment of HCC in your region? Please include the % of patients treated per systemic therapy.

6 Other systemic therapies used in first line treatment of HCC % of patients treated per systemic therapy ) In your region, how are patients treated after Sorafenib failure in HCC first line setting? Enrolment Questions

7 10) As used in the synopsis, would institutions in your region be able and willing to recruit patients into the following first line treatment regimens in HCC setting: Yes No Durvalumab + Tremelimumab? Durvalumab Monotherapy? Tremelimumab Monotherapy? Sorafenib 400mg BID Monotherapy? ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) If you answered NO to any of the below, please provide further details of why you would be unable to recruit patients into a specific regimen. Please provide proposed solution-if possible.

8 11) Based on specific laboratory entry criteria (below for your reference) are there any criteria that you feel would make enrollment more challenging in your region? ALT/AST: 5 ULN; Serum bilirubin: 2.0 ULN; Platelet count: /L; HBV: Subjects with concomitant HBV infection must have a confirmed diagnosis of HBV characterized by the presence of anti-hbc, and be sufficiently suppressed with active antiviral treatment such that HBV DNA < 2000 IU/mL; HCV: Subjects with concomitant HCV infection must have confirmed diagnosis of HCV characterized by the presence of detectable HCV RNA or anti-hcv antibody upon enrollment.

9 Are there any other laboratory entry criteria that you feel would make enrollment more challenging in your region? Please specify and explain below: 12) Do you feel that excluding patients in Child-Pugh class B7 would significantly reduce the overall enrollment rate in your region? If yes, please describe impact on enrollment:

10 13) After reviewing the inclusion and exclusion criteria specific to the patient populations targeted for this study, are there any criteria that will make it difficult for sites to enroll patients in your country? Please explain the reason and provide proposed changes. 14)

11 Are there any constraints that would not reduce your planned recruitment targets, but that the operations team and cluster heads/country heads need to be aware of to proactively mitigate (ie, resource, lack of available sites, need for external vendor support, etc.)? Please specify: 15) Taking into consideration a CTA package available end of February 2017, please provide an estimated first site ready to enroll and first subject in dates for your country. First site ready to enroll: First Subject:: 16)

12 Are there any competing studies underway (i.e. Checkmate 459), or scheduled to start in your country, during the timeframe of this study (May Nov2018)? If yes, assess impact on patient availability: 17) Are there any product launches underway or expected to start in your country during the timeframe of the study (May Nov2018)?

13 If yes, please assess the impact on patient availability. 18) Is there anything else regarding the competitive landscape in your country that you feel is relevant for the Global Team to be aware of? Please specify:

14 19) Any other comments, recommendations or information that you would like the project team to be aware of regarding this study? Recruitment 20) To help us better estimate initial study timelines and budget, please provide the expected screen failure rate for your country. 21) To help us better estimate initial study timelines and budget; with the planned recruitment period of May 2017 to November 2018, how many randomized subjects per month can your country contribute to this study?

15 22) To help us better estimate initial study timelines and budget, how many study sites are needed to meet the recruitment targets in the previous question? 23) Based on your experience with other IO studies, please provide the top 3 factors that negatively impacted enrollment in your region. Factor 1: Factor 2: Factor 3: What recommendations do you have to resolve these factors? 24) Based on your experience with other IO studies, please provide the top 3 factors that negatively impacted study start-up in your region.

16 Factor 1: Factor 2: Factor 3: What recommendations do you have to resolve these factors? 25) Based on your experience with other IO studies, please provide the top 3 factors that negatively impacted study site activation in your region. Factor 1: Factor 2: Factor 3: What recommendations do you have to resolve these factors?

17 26) Is obtaining a tumor biopsy for metastatic/advanced disease (any viable sample, not necessarily primary liver lesion) standard practice in your region? Comments: 27) If the study requires patients to have a recent biopsy ( 3 years) or a fresh one on screening, will this requirement be an enrollment challenge?

18 If yes, please describe impact on enrollment. 28) Are your sites able to ship tumour tissue samples to a central lab (possibly to another country) for testing? 29) Is there any regulatory approval required on the samples export?

19 If yes, please specify the requirements, and the timelines for application. Please specify the requirements: Please specify the timelines for application:: 30) The study assessment schedule requires tumour assessment to be made using CT/MRI every 8 weeks for first 48 weeks and 12 weeks thereafter. Do you foresee any challenges with this proposed scan schedule?

20 If yes, please describe challenges and provide proposed solutions. 31) An independent Central Review (ICR) of radiological scans may be planned for this study. Do you foresee any issues in providing all scans (CTs/MRIs) for central review? If yes, please describe issues and provide proposed solutions:

21 32) This study plans to use electronic transfer of radiological scans to PAREXEL. Do your sites have any experience using the PAREXEL electronic transfer (etransfer) OR a similar technology? Please highlight any challenges you foresee with using etransfer and provide proposed solution: 33)

22 If the protocol were to require sites to submit scans for central eligibility review through etransfer within 48 hrs of acquisition, would you foresee any challenges with this proposed timeline? If yes, please describe challenges and provide proposed solutions: 34) Are there any major challenges or risks that you foresee that may affect recruitment in your region?

23 If yes, please describe challenges and provide proposed solutions: 35) Are there other criteria that we have not considered that you feel may be relevant in this patient population? If yes, please describe criteria:

24 Standard of Care Questions 36) Is sorafenib approved for use in your country? 37) If sorafenib is not approved for first line treatment of HCC patients, but is approved for other indications in your country, can it be locally sourced for a first line HCC clinical trial?

25 38) Are sites able and willing to provide sorafenib locally (ie: there are no local regulations that prevent this)? If yes, would sites expect reimbursement for Sorafenib? What is the expected cost of reimbursement for Sorafenib based on study design? If no, is it possible to organize local purchasing and distribution of Sorafenib in your market?

26 39) If local supplies are used, is there a requirement for "clinical trial use only" identifier labels to be provided by the sponsor? If yes, is it possible for these labels to be applied to locally sourced Sorafenib? 40) How many cycles of treatment do HCC patients in first line setting typically receive?

27 Thank You! Thank you for taking the time to complete this survey. Should you have any questions, please contact us at: