SUMMARY OF CHANGES Amendment 6, Version Date: March 29, 2010 [Broadcast: April 8, 2010]

Transcription

1 Amendment 6, Version Date: March 29, 2010 [Broadcast: April 8, 2010] RTOG 0233, "A Phase II Randomized Trial for Patients With Muscle-Invading Bladder Cancer Evaluating Transurethral Surgery and BID Irradiation Plus Either Paclitaxel and Cisplatin or 5-Fluorouracil and Cisplatin Followed by Selective Bladder Preservation and Gemcitabine/Paclitaxel/Cisplatin Adjuvant Chemotherapy" RTOG 0233 has been amended as follows: As mandated by CTEP, CTC version 2.0 reporting requirements were converted to CTCAE version 4.0. Section 7.12 was revised to reflect this change.

2 Amendment #5, Version Date: May 9, 2008 (Broadcast Date: May 22, 2008) RTOG 0233, "A Phase II Randomized Trial for Patients With Muscle-Invading Bladder Cancer Evaluating Transurethral Surgery and BID Irradiation Plus Either Paclitaxel and Cisplatin or 5-Fluorouracil and Cisplatin Followed by Selective Bladder Preservation and Gemcitabine/Paclitaxel/Cisplatin Adjuvant Chemotherapy" RTOG 0233 has been amended as follows: Title Page: Was reformatted to include the RTOG Statistician's contact information. Index: Appendix IV, "Toxicity Criteria," was removed from the protocol and is now "Small Pelvic Fields;" the subsequent Appendices were renumbered. Schema: The schema table was reformatted, so that under Consolidation Therapy (Weeks 8, 9), Arm 1 ("c") and Arm 2 ("d"), the X's in the final row (Pelvic XRT, bid x 8 days) are properly aligned with the "Day" column numbers. Section 5.3: The CTSU hours of operation were updated. Sections and : All REFERENCES to Appendix VI were changed to Appendix IV, which is now the "Small Pelvic Fields" Appendix. Sections 7.12 and 7.13: Were revised to include the current RTOG Adverse Event reporting guidelines. Section 8.1.1: The reference to Appendix VII was revised to Appendix V, which is now the "Cystoscopy Report Form" Appendix. Sections 10.3, 10.4, and 10.5: Were updated to reflect the new RTOG Biospecimen Resource, including the new mailing address, address, and phone/fax numbers. Section : The CDUS monitoring text was added (moved from Section 7.12) and the CDUS version was updated to 3.0 per current RTOG standard. Consent (Appendix IA): Under "What Is Involved In The Study?", Treatment 1 and Treatment 2, the timing of the drug and radiation treatments was revised for consistency with Section of the protocol.

3 Appendix IV, V, and VI: Appendix IV is now "Small Pelvic Fields" and Appendix V is now "Cystoscopy Report Form". The "Adverse Reaction Reporting Guidelines" Appendix (formerly Appendix V) was deleted; this information is detailed in Sections 7.12 and 7.13.

4 Update Date: May 11, 2006 RTOG 0233, "A Phase II Randomized Trial for Patients with Muscle-Invading Bladder Cancer Evaluating Transurethral Surgery and BID Irradiation plus either Paclitaxel and Cisplatin or 5-Fluorouracil and Cisplatin Followed by Selective Bladder Preservation and Gemcitabine/Paclitaxel/Cisplatin Adjuvant Chemotherapy" RTOG 0233 has been updated as follows: Section : The contact information for central review and tissue submission (LDS Hospital in Utah) was changed to reflect the new mailing address, addresses and phone numbers. NOTE: This is an editorial/administrative change to the Protocol. NCI now requires that these changes be documented on the Protocol title page with the date of the update noted as "Update Date". An updated Protocol is available (no password required) on the RTOG website:

5 Amendment #4, Version Date: April 18, 2006 RTOG 0233, "A Phase II Randomized Trial for Patients With Muscle-Invading Bladder Cancer Evaluating Transurethral Surgery and BID Irradiation Plus Either Paclitaxel and Cisplatin or 5-Fluorouracil and Cisplatin Followed by Selective Bladder Preservation and Gemcitabine/Paclitaxel/Cisplatin Adjuvant Chemotherapy" RTOG 0233 has been amended as follows: Schema: The time frame for treatment start was amended from "4-8 weeks" to "within 8 weeks of the TUR" for consistency with the eligibility. Eligibility Checklist - Page 1 of 2: Question #12, "of the" replaced "post" in the sentence: "Will treatment start within 8 weeks of the TUR and endoscopic evaluations?" for consistency with the eligibility. Section 3.1.6: "of the" replaced "following" in the sentence: "Protocol treatment to begin within 8 weeks of the transurethral resection and endoscopic evaluation" for consistency with the eligibility. Section 5.3: Updated the zip code for CTSU to Section 6.0: Second sentence in the first paragraph: "of the" replaced "following" in, "This regimen will begin within 8 weeks of the TUR" for consistency with the eligibility. Section 7.1.2: Under "Arm 2", "of the" replaced "following" in the sentence, " within 8 weeks of the transurethral resection (TUR)" for consistency with the eligibility. Sections and : "p" was removed from the T staging group for consistency with the AJCC Staging System in Appendix III. Consent Form: Under "WHAT IS INVOLVED IN THE STUDY?", second paragraph, last sentence was amended to read, "within 8 weeks of the resection" for consistency with the eligibility. Under "HOW LONG WILL I BE IN THE STUDY?", first paragraph, second sentence was amended to read, "within 8 weeks of the transurethral bladder resection" for consistency with the eligibility. We will tell you about new information that may affect your health, welfare, or willingness to stay in this study" was amended to read, "A group of experts in bladder cancer from the RTOG Genitourinary Committee, the study chairs,

6 and the statistician will be reviewing the data periodically from this research throughout the study. We will tell you about the new information from this or other studies that may affect your health, welfare, or willingness to stay in this study" to avoid ambiguity. An updated protocol is available (no password required) on the RTOG website:

7 Update Date: December 1, 2004 RTOG 0233, A Phase II Randomized Trial for Patients With Muscle-Invading Bladder Cancer Evaluating Transurethral Surgery and BID Irradiation Plus Either Paclitaxel and Cisplatin or 5-Fluorouracil and Cisplatin Followed by Selective Bladder Preservation and Gemcitabine/Paclitaxel/Cisplatin Adjuvant Chemotherapy RTOG 0233 has been updated as follows: Section : The address for LDS Hospital was changed to reflect a new address. NOTE: This is an editorial/administrative change to the protocol. NCI now requires that these changes be documented on the protocol title page with the date of the update noted as "Update Date," not as an amendment. An updated protocol is available (no password required) on the RTOG website: SUMMARY OF CHANGES Amendment #3, Version Date: October 28, 2004 RTOG 0233, A Phase II Randomized Trial for Patients With Muscle-Invading Bladder Cancer Evaluating Transurethral Surgery and BID Irradiation Plus Either Paclitaxel and Cisplatin or 5-Fluorouracil and Cisplatin Followed by Selective Bladder Preservation and Gemcitabine/Paclitaxel/Cisplatin Adjuvant Chemotherapy RTOG 0233 has been amended as follows: Section 6.2.1: The time frame for the start of consolidation therapy was changed to 7-14 days for consistency with information elsewhere in the protocol.

8 The phrase with an interfraction period of at least 4-6 hours was added at the end of the section for clarity. Section 7.1.2: The word be was added after should for clarity. Section : The time frame for the start of consolidation therapy was changed to 7-14 days for consistency with information elsewhere in the protocol. Section : For increased accuracy, the first row of values in the hematologic toxicity table was altered and an additional row of values was added. The first two rows of values now read as follows: Percent of Full Dose AGC (x 10 9 /L) Platelets (x 10 9 /L) Gemcitabine Paclitaxel > 1.2 > to 1.19 or 75 to Section : The mailing address for RTOG Headquarters was updated. The address also was updated in , , and Section 11.1: An X corresponding with footnote b was added to the post-cystectomy or post consolidation chemo column in the cystoscopy row for consistency with information elsewhere in the protocol. Appendix IA: Under What Is Involved in the Study? / Treatments 1 and 2: In the first sentence of the section, the phrase and a pelvic CT scan was deleted for consistency with information elsewhere in the protocol. The sentence now reads: Three weeks after the completion of chemotherapy and radiation, the surgeon will re-examine your bladder through the fiberoptic scope and a biopsy will be done. In the portion of the section that begins If you take part in this study, you will also have the following tests and procedures: o First bullet for clarity, the word a was added before fiberoptic scope and the phrase if you have not had your bladder removed was added after at follow-up visits. o Third bullet for clarity, the phrase if you have not had your bladder removed was added after during additional chemoradiotherapy. o Fifth bullet for consistency with information elsewhere in the protocol, the phrase 3 weeks after chemotherapy was deleted. An updated protocol is available (no password required) on the RTOG website:

9 Update Date: July 14, 2004 RTOG 0233, A Phase II Randomized Trial For Patients With Muscle-Invading Bladder Cancer Evaluating Transurethral Surgery And BID Irradiation Plus Either Paclitaxel And Cisplatin Or 5-Fluorouracil And Cisplatin Followed By Selective Bladder Preservation And Gemcitabine/Paclitaxel/Cisplatin Adjuvant Chemotherapy RTOG 0233 has been updated as follows: Section 11.1 Study Parameters For clarity, the Post Cystectomy column was changed to include Post Cystectomy Or Post Consolidation Chemo. NOTE: This is an editorial/administrative change to the protocol. NCI now requires that these changes be documented on the protocol title page with the date of the update noted as Update Date, not as a revision. An updated protocol is available (no password required) on the RTOG website:

10 Amendment 2-: June 4, 2004 RTOG 0233, A Phase II Randomized Trial For Patients With Muscle-Invading Bladder Cancer Evaluating Transurethral Surgery And BID Irradiation Plus Either Paclitaxel And Cisplatin Or 5-Fluorouracil And Cisplatin Followed By Selective Bladder Preservation And Gemcitabine/Paclitaxel/Cisplatin Adjuvant Chemotherapy RTOG 0233 has been updated as follows: Schema Eligibility: Protocol treatment was changed to allow to begin within 8 weeks following transurethral resection and endoscopic evaluation. Eligibility Checklist Step 1 (Induction) Question 12. Treatment will be allowed to start 8 weeks post TUR. Section Protocol treatment was changed to allow to begin within 8 weeks following transurethral resection and endoscopic evaluation. Sections and The criteria for cisplatin 50% dose reduction during adjuvant chemotherapy has been changed from a creatinine clearance between ml/min to ml/min. This adjustment was made because the accepted range for creatinine clearance is >60 ml/min. Section 11.1 Study Parameters Due to an error in the writing of the protocol, the CT scan schedule has been changed. Scans are to be repeated after consolidation, at the time of re-evaluation, not at the completion of induction treatment. The Eastern Cooperative Oncology Group (ECOG) is participating in the study. At ECOG s request, the ECOG study number and Co-Chair were added to the title page and the following sections were added for ECOG Investigators: Sections 5.3, , 10.6, and In addition, the following sections were revised for ECOG Investigators: Sections 6.0, 7.0, and Appendix IA, under What About Confidentiality?.

11 Revision 1, Version Date: February 3, 2003 RTOG 0233, A Phase II Randomized Trial For Patients With Muscle-Invading Bladder Cancer Evaluating Transurethral Surgery And BID Irradiation Plus Either Paclitaxel And Cisplatin Or 5-Fluorouracil And Cisplatin Followed By Selective Bladder Preservation And Gemcitabine/Paclitaxel/Cisplatin Adjuvant Chemotherapy IRB Review Requirements: ( ) Full board review required (X) Expedited review allowed; however, site IRB requirements take precedence. ( ) No review required The following changes have been made to Appendix IA, the sample consent: Under What Is Involved In The Study?, Treatment 1 and 2, the sentence You will receive cisplatin twice each week has been corrected to You will receive cisplatin three days a week to be consistent with the Induction Therapy described in the Schema and with Section 7.1 Under What is Involved In the Study?, Treatment 2, the sentence You will also receive 5-Fluorouracil once a day on the first four days of your radiation treatment has been corrected to You will also receive 5-Fluorouracil three days a week by injection over 24 hours into a vein (intraveneously) during the first and last week of your radiation treatment to be consistent with the Induction Therapy described in the Schema and with Section 7.1. A revised protocol is available (no password required) on the RTOG website:

12 Update Date: December 13, 2002 RTOG 0233, A Phase II Randomized Trial For Patients With Muscle-Invading Bladder Cancer Evaluating Transurethral Surgery And BID Irradiation Plus Either Paclitaxel And Cisplatin Or 5-Fluorouracil And Cisplatin Followed By Selective Bladder Preservation And Gemcitabine/Paclitaxel/Cisplatin Adjuvant Chemotherapy RTOG 0233 has been updated as follows: Eligibility Checklist The operational/demographic portions of the checklist were updated as follows: Step 1 (Induction), Page 2: Question # 16, asking that the patient s T stage be specified, was added; Question #17, asking that the Medical Oncologist be specified, was added; Subsequent questions were renumbered appropriately. Step 2 (Consolidation), Page 1: Question # 8, asking that the patient s induction treatment assignment be specified, was added; Subsequent questions were renumbered appropriately. NOTE: This is an editorial/administrative change to the protocol. NCI now requires that these changes be documented on the protocol title page with the date of the update noted as Update Date, not as a revision. An updated protocol is available (no password required) on the RTOG website: