SUMMARY OF CHANGES
Update Date: February 2, 2005
RTOG BR-0118, A PHASE III STUDY OF CONVENTIONAL RADIATION THERAPY PLUS THALIDOMIDE (NSC# 66847) VERSUS CONVENTIONAL RADIATION THERAPY FOR MULTIPLE BRAIN METASTASES
Study Chair: Jonathan Knisely, M.D., (203) 785-2960; FAX # (203) 785-4622; jonathan.knisely@yale.edu
RTOG BR-0118 was updated as follows:
Title Page: The Quality of Life Chair information was changed to reflect Benjamin Movsas, M.D. as the new Chair.
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: http://www.rtog.org/
SUMMARY OF CHANGES
Update Date: February 2, 2004
RTOG BR-0118, A PHASE III STUDY OF CONVENTIONAL RADIATION THERAPY PLUS THALIDOMIDE (NSC# 66847) VERSUS CONVENTIONAL RADIATION THERAPY FOR MULTIPLE BRAIN METASTASES
Study Chair: Jonathan Knisely, M.D., (203) 785-2960; FAX # (203) 785-4622; jonathan.knisely@yale.edu
RTOG BR-0118 was updated as follows:
Section 7.3: The reference to NCI Common Toxicity Criteria Version 2.0 was deleted and replaced with Common Terminology Criteria for Adverse Events Version 3.0 to be consistent with the rest of the protocol.
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: http://www.rtog.org/
SUMMARY OF CHANGES
Revision 4, October 31, 2003
RTOG BR-0118, A PHASE III STUDY OF CONVENTIONAL RADIATION THERAPY PLUS THALIDOMIDE (NSC# 66847) VERSUS CONVENTIONAL RADIATION THERAPY FOR MULTIPLE BRAIN METASTASES
Study Chair: Jonathan Knisely, M.D., (203) 785-2960; FAX # (203) 785-4622; jonathan.knisely@yale.edu
IRB Review Requirements:
( ) Full board review required
( X ) Expedited review allowed, however, site IRB requirements take precedence
( ) No review required
RTOG BR-0118 was revised in response to the NCI required conversion from CTC v2.0 to CTCAE v3.0. The projected implementation date is December 19, 2003. This protocol will use CTC v2.0 for AE reporting through December 18, 2003. From December 19, 2003 forward this protocol will utilize CTCAE v3.0 for AE reporting.
The following changes were made to the to the protocol to accomplish this conversion:
Title Page: Version Date changed to October 31, 2003
Index: Appendix III and Appendix IV were deleted as the reporting guidelines are provided within the protocol. As a result, Appendix V was renumbered as Appendix III.
Section 6.7: The word “acute” was deleted from the heading because this section is no longer including acute radiation toxicities.
Section 6.7.2: The new section “Radiation Toxicity Reporting” using the CTCAE v3.0 was added to replace the previous Sections 6.7.2 and 6.7.3, which used CTC v2.0.
Section 7.8: The new section “Adverse Event Reporting” using the CTCAE v3.0 was added to replace the previous section 7.8, which used CTC v.2.0
These are additional changes that were made to the protocol:
Section 6.6: The word “initial” was deleted from the first sentence because films of initial fields are not collected.
Section 12.0: Under “Due” “At completion of RT” was deleted because it is redundant.
SUMMARY OF CHANGES
Revision 3, September 25, 2003
RTOG BR-0118, A PHASE III STUDY OF CONVENTIONAL RADIATION THERAPY PLUS THALIDOMIDE (NSC# 66847) VERSUS CONVENTIONAL RADIATION THERAPY FOR MULTIPLE BRAIN METASTASES
Study Chair: Jonathan Knisely, M.D., (203) 785-2960; FAX # (203) 785-4622; jonathan.knisely@yale.edu
IRB Review Requirements:
( ) Full board review required
( X ) Expedited review allowed, however, site IRB requirements take precedence
( ) No review required
RTOG BR-0118 was revised in response to the memo from Dr. Howard Streicher regarding the development of renal dysfunction. The following sections of the protocol have been added:
Section 7.2.7.7 The risk of renal dysfunction may be increased when thalidomide is used in combination with zoledronic acid (Zometa) as indicated in the zoledronic acid package insert. Although described only in myeloma, this precaution could apply to other situations with impaired renal function and/or hypercalcemia.
Appendix I, sample consent: Under “Risks from Thalidomide”: The risk of kidney problems may be increased when zoledronic acid (Zometa) is used in combination with thalidomide. Although this warning, which is indicated
on the drug information (a piece of paper) inserted in the package of zoledronic acid, has been described only in
patients with myeloma (a type of cancer in the bone and bone marrow), it could apply to other situations when
these drugs are used in patients with kidney problems and/or hypercalcemia (too much calcium in the blood).
SUMMARY OF CHANGES
Revision 2, Version Date: October 17, 2002
RTOG BR-0118, A Phase III Study Of Conventional Radiation Therapy Plus Thalidomide (NSC # 66847) Versus Conventional Radiation Therapy For Multiple Brain Metastases
Study Chair: Jonathan Knisely, M.D., (203) 785-2960; FAX # (203) 785-4622; jonathan.knisely@yale.edu
IRB Review Requirements:
(X) Full board review required
( ) Expedited review allowed
( ) No review required
In response to NCI’s recent thalidomide IND Safety Report, at the recommendation of the ACR IRB, and in response to the Data Monitoring Committee’s recommendation that RTOG stress to sites the need for rapid reporting of such serious adverse events, the following sections of the protocol have been revised:
- Section 7.2.6 — The phrase “or bradycardia” was added after “tachycardia”, and the last two sentences in the section were added.
- Section 7.8.3 — A statement was added concerning the discontinuation of thalidomide in a patient experiencing a confirmed thromboembolic event; a statement was added requiring sites to report all grades of any thromboembolic event to RTOG Headquarters within 48 hours of such an event; this statement also was added to Appendix IV, “Adverse Reaction Reporting Guidelines”, under “C”.
- Section 11.2.6 was added.
Appendix I, sample consent — Under “Risks from Thalidomide”, four risks, including “Blood clots in legs and lungs”, were revised from “Less Likely” to “Less Likely But Serious”; the risk of “Problems with heart or lung function from blood clots moving from the veins in the body to the lungs” was added under “Rare”; the sentence, “Thalidomide has been found in the semen of men taking thalidomide”, was added to the 4th paragraph under the lists of risks from Thalidomide.
Other Changes
Section 4.1.5 — After discussion, the study and site chairs have decided to provide more time between the imaging study and enrollment in order to offer treatment to more patients; therefore, the MRI with contrast is now required within 21 days versus 10 days.
A revised protocol is available (no password required) on the RTOG website: http://www.rtog.org/
SUMMARY OF CHANGES
Revision 1, June 10, 2002
RTOG BR-0118, A PHASE III STUDY OF CONVENTIONAL RADIATION THERAPY PLUS THALIDOMIDE (NSC# 66847) VERSUS CONVENTIONAL RADIATION THERAPY FOR MULTIPLE BRAIN METASTASES
Study Chair: Jonathan Knisely, M.D., (203) 785-2960; FAX # (203) 785-4622; jonathan.knisely@yale.edu
IRB Review Requirements:
(X) Full board review required
( ) Expedited review allowed
( ) No review required
RTOG BR-0118 has been revised as follows:
The starting dose and dose escalation of thalidomide have been changed; thalidomide will start at 200 mg/night and escalate by 200 mg weekly during radiation therapy and by 200 mg every 2 weeks after radiation therapy. The following sections were revised for this change: Schema, footnote “b”; Section 7.1; and Appendix I, under “What Is Involved In The Study”, Treatment 2.
Further information regarding drug-induced somnolence has been added in the following sections: Section 7.2.6, following “somnolence”, addition of the parenthetical phrase “(referred to as “depressed level of consciousness” in the NCI Common Toxicity Criteria)”; Section 7.3, 3rd and 4th paragraphs; Section 9.0, 4th paragraph.
Section 11.1 — Footnote “b” was revised and footnote “j” was added to clarify the timeframe for laboratory studies; this clarification also was made in Section 11.2.5; footnote “k” was added to correspond to the timeframe for follow up in Section 12.1.
Appendix I, sample consent — Under “How Long Will I Be In This Study”, the timeframe for follow up was revised to correspond with Sections 11.1 and 12.1; under “What Are The Risks Of The Study”, the risks associated with thalidomide were revised to better correspond to Section 7.2.6.
A revised protocol is available (no password required) on the RTOG website: http://www.rtog.org/