SUMMARY OF CHANGES
Amendment #2, Version Date: December 11, 2007

RTOG 0625, A Randomized Phase II Trial of Bevacizumab With Irinotecan or Bevacizumab With Temozolomide in Recurrent Glioblastoma

Study Chair: Mark R. Gilbert, MD; 713-792-4008; mrgilbert@mdanderson.org


RTOG 0625 has been amended as follows:

Eligibility Checklist page 2 of 3: A new question # 26 was added to correspond with new Section 3.2.10.

Section 3.2.10: This criterion was added due to the black box warning of nephrogenic systemic fibrosis with gadolinium-based contrast agents in patients with severe kidney disease.

Section 7.2.9: The updated CAEPR for Bevacizumab (NSC 704865) version 1.2, June 19, 2007 replaced the previous CAEPR.

Section 11.2.2

Section 12.2: For increased clarity,


Appendix I: Consent for Participation in Advanced MRI Study

Appendix II: Study Parameter Table: To clarify the timeline for the standard and advanced MRIs, the last two rows were reorganized and the footnotes corresponding to the standard and advanced MRIs (footnotes f and g) were rewritten.

Appendix V: MRI Technical Acquisition Instructions: For increased clarity, the first sentence was rewritten and the last sentence was deleted.

Appendix VI: Imaging Study Submission and Review

To reflect current protocol logistics: in 2.2 Electronic Transfer of MRI Images, "and Raw Spectroscopy Data" was added to the title; the first sentence was deleted; "and raw MRS data files" was added to the second sentence; and the third sentence was added.

Appendix VII: ACRIN Advanced Imaging Adverse Event Reporting Instructions: Contact information was updated in the following places:







SUMMARY OF CHANGES
Update Date: August 9, 2007

RTOG 0625, A Randomized Phase II Trial of Bevacizumab With Irinotecan or Bevacizumab With Temozolomide in Recurrent Glioblastoma

Study Chair: Mark R. Gilbert, MD; 713-792-4008; mrgilbert@mdanderson.org


RTOG 0625 has been updated as follows:

Eligibility Checklist, question 21: The question concerning standard of care MRIs (added as question 21 in Amendment 1) was moved to the last question (current question 26) due to database needs. All affected questions were appropriately re-numbered.

Appendix I: Main Study Consent
Appendix II: Study Parameter Table
SUMMARY OF CHANGES
Amendment #1, Version Date: July 18, 2007

RTOG 0625, A Randomized Phase II Trial of Bevacizumab With Irinotecan or Bevacizumab With Temozolomide in Recurrent Glioblastoma

Study Chair: Mark R. Gilbert, MD; 713-792-4008; mrgilbert@mdanderson.org


RTOG 0625 has been amended as follows:

Table of Contents
Eligibility Checklist, Question 2, page 1: The former question 2 was deleted and moved to the second part of the eligibility checklist (question 26, page 3) due to database needs. Subsequent questions were appropriately renumbered.

Eligibility Checklist, Question 21, page 2: The former question 21 was deleted and moved to the second part of the eligibility checklist (question 21, page 3) due to database needs. Subsequent questions were appropriately renumbered.

Eligibility Checklist, Question 22, page 3: Wording was revised to clarify that the patient is agreeing to participate in the advanced imaging component of ACRIN 6677.

Section 2.3: Objectives for Central MRI Review were added. Subsequent sections were appropriately renumbered.

Section 2.4.1: For increased clarity and consistency with other sections of the protocol, "after two weeks of treatment" was changed to "after 2 weeks following initiation of treatment."

Section 2.4.2: For increased clarity and consistency with other sections of the protocol, "2 weeks after treatment" was changed to "2 weeks following initiation of protocol treatment" and "every" was added before "2 cycles of treatment."

Section 3.1.22: The cross reference to Section 5.2.1 was corrected to 5.2.

Section 3.2.3.3: A timeframe of within 6 months was added for consistency with the timeframe in Section 3.2.3.5.

Section 5.2
Section 5.2.1: This section was revised for increased clarity.

Section 5.2.2: For increased clarity and accuracy, in the second sentence, "qualification" was changed to "image quality review" and reference to the ACRIN website was deleted.

Section 7.3.9: Neurologic adverse events were added for consistency with the informed consent.

Section 7.5.3.1: The statement in the "Remarks" column of the last row was deleted because it was included in error.

Section 7.8.4: Information was added for adverse event reporting for the magnetic resonance imaging protocol.

Sections 10.2-10.4: Tissue submission logistics were rewritten so that institutions submit all material directly to Dr. Aldape.

Section 11.2.2
Section 11.2.2.1: For increased clarity "qualification" was changed to "imaging quality assurance review" in the title and first sentence.

Section 13.1.3: Endpoints for Central MRI Review were added. Subsequent sections were appropriately renumbered.

Section 13.1.4.1: For increased clarity and consistency with other sections of the protocol, "2 weeks after chemotherapy" was changed to "2 weeks following initiation of chemotherapy."

Section 13.1.4.2: For increased clarity and consistency with other sections of the protocol, "2 weeks after treatment" was changed to "2 weeks following initiation of protocol treatment" and "every" was added before "2 cycles of treatment."

Section 13.2.1.3

" In the first sentence, Section 13.4.2 was corrected to Section 13.5.2.

In the last sentence, "temozolomide and irinotecan" was corrected to "bevacizumab and irinotecan."

Section 13.5.4: Statistical methods were added for central MRI review to provide explicit information for this component of the trial. Subsequent sections were appropriately renumbered.

Section 13.5.5
Appendix I: Main Study Consent
Appendix I: Consent for Participation in Advanced MRI Study
Appendix II: Study Parameter Table
Appendix V: MRI Technical Acquisition Instructions: The imaging parameters were removed and a reference to see the ACRIN website was added.

Appendix VI: Imaging Study Submission and Review
Appendix VII: ACRIN Advanced Imaging Adverse Event Reporting Instructions
Appendix VIII: Imaging Reimbursement


SUMMARY OF CHANGES
Update Date: March 1, 2007

RTOG 0625, A Randomized Phase II Trial of Bevacizumab With Irinotecan or Bevacizumab With Temozolomide in Recurrent Glioblastoma

Study Chair: Mark R. Gilbert, MD; 713-792-4008; mrgilbert@mdanderson.org


To clarify the ACRIN imaging component of this trial, RTOG 0625 has been updated as follows:

Index: Appendices VI, VII, VIII re-titled per changes described below.

Eligibility Checklist, question 21: Added. All subsequent questions re-numbered.

Section 3.1.22: Added.

Sections 5.2-5.2.2: Re-written.

Section 5.3: First paragraph re-written.

Section 11.2.2: Appendix cross-reference corrected.

Section 11.2.2.1: Added.

Section 11.2.3: Appendix cross-reference corrected.

Section 11.2.4: Appendices cross-references corrected.

Section 12.2: Due dates for MRIs corrected.

Appendix II: Footnote f re-written.

Appendix VI:
Appendix VII:
Appendix VIII:


The following additional changes were made:

Cover page: Phone number for Dr. Gilbert updated.

Schema page: Arm 2 cycle length corrected for consistency with the rest of the protocol.