SUMMARY OF CHANGES
Update: April 3, 2008
(Broadcast date: April 3, 2008)

RTOG 0232, "A Phase III Study Comparing Combined External Beam Radiation and Transperineal Interstitial Permanent Brachytherapy With Brachytherapy Alone for Selected Patients With Intermediate Risk Prostatic Carcinoma"

Study Chair: Bradley R. Prestidge, M.D., (210) 247-0888, bprestidge@texascancerclinic.com


RTOG 0232 has been updated as follows:

Section 10: As a result of the relocation Biospecimen Resource to the University of California San Francisco, the updated information was incorporated throughout this section and in Appendix XIII.

Section 12.1: The "NOTE" has been updated for clarity.

Section 12.2.2: "Preliminary Dosimetry Information" has been deleted as it is no longer to be collected. Under "Final Dosimetry Information," "Copy to ITC and RTOG HQ" was added for form T1 and Daily Treatment Record; the other items were deleted.

Appendix XIII: The CTSU hours of operation were updated.





SUMMARY OF CHANGES
Amendment #4, Version Date: January 11, 2008
(Broadcast date: April 3, 2008)

RTOG 0232, "A Phase III Study Comparing Combined External Beam Radiation and Transperineal Interstitial Permanent Brachytherapy with Brachytherapy Alone for Selected Patients with Intermediate Risk Prostatic Carcinoma"

Study Chair: Bradley R. Prestidge, MD; (210) 247-0888; bprestidge@texascancerclinic.com


RTOG 0232 has been amended as follows:

Title Page: The contact information for Drs. Amin and Sanda has been updated. Dr. Sanda's contact information was also updated in Appendix IX.

Schema Page: The required sample size was changed to 586 to correspond with other changes to the protocol.

Section 1.1: A sentence was added at the end of the third paragraph.

Section 2.0: Changes were made to this section to change the primary endpoint to a more treatment related outcome, freedom from progression. A new section number 2.2.2 was added for clarity.

Section 6.4: This section was revised to reflect current RTOG radiation adverse event reporting.

Section 10.3.4: The email address for the tissue bank was updated.

Section 11.3.4: This section was deleted and the following section renumbered.

Section 11.3.7: This section number was added for clarity and "determined by radiographic criteria and/or tissue confirmation" was added at the end of the section.

Section 11.3.8: "Overall" was added to the heading.

Section 12.1: Form FF was deleted.

Section 13.1: The study endpoints were revised to correspond to the new primary endpoint in Section 2.0.

Section 13.2.2: This section was revised corresponding to the changes to sample size and endpoints.

Section 13.2.5: In the last paragraph, the numbers of eligible cases were revised corresponding to other changes to the protocol.

Section 13.3: This section was revised to reflect the change in projected accrual. Section 13.3.1 was deleted.

Section 13.4: A new sentence was added under the heading for this section. The text for Section 13.4.1 was revised.

Section 13.4.4.1: The heading was changed to "Primary Endpoint: Freedom from Progression," and the section was entirely rewritten.

Section 13.4.4.2: The heading was changed to "Time to Biochemical Failure-Related Endpoints." The first sentence was revised and the second sentence was deleted. In the third, fourth, and fifth sentences, PSA was deleted: in the seventh sentence, "7th year" was deleted; a new last sentence was added.

Sections 13.4.4.3 and 13.4.4.4: These new sections were added.

Section 13.4.5: This section was extensively revised.

Section 13.5: The table at the end of this section was revised to reflect the change in sample size.

REFERENCES: The REFERENCES were renumbered as necessitated by changes made to the text of the protocol. Corresponding cross REFERENCES within the text were revised also.

Consent: Under "How Many People Will Take Part In The Study," the sample size was changed to correspond with the change to the protocol.





SUMMARY OF CHANGES
Amendment 3, Version Date: January 24, 2007

RTOG 0232, "A Phase III Study Comparing Combined External Beam Radiation and Transperineal Interstitial Permanent Brachytherapy with Brachytherapy Alone for Selected Patients with Intermediate Risk Prostatic Carcinoma"

Study Chair: Bradley R. Prestidge, MD; (210) 247-0888; bprestidge@texascancerclinic.com


At the request of the Cancer Trials Support Unit (CTSU), RTOG 0232 has been amended as follows:

Title page: The statement at the bottom of the page regarding patient enrollments from non-RTOG Cooperative Group members was deleted, and text was added to the subsequent page.

Appendix XIII: All prior CTSU logistics text was deleted and was replaced with new CTSU logistics.



SUMMARY OF CHANGES
Update Date: February 16, 2006

RTOG 0232, "A Phase III Study Comparing Combined External Beam Radiation and Transperineal Interstitial Permanent Brachytherapy With Brachytherapy Alone for Selected Patients With Intermediate Risk Prostatic Carcinoma"

Study Chair: Bradley R. Prestidge, M.D., (210) 247-0888, bprestidge@texascancerclinic.com


RTOG 0232 has been updated as follows:

Title page: Contact information was updated for Deborah Watkins Bruner

Eligibility checklist, page 2, question 20: Due to inadvertent omissions:

Section 5.1.2:Verbiage regarding advanced technology techniques was clarified.

Section 5.1.2.1: Verbiage regarding advanced technology techniques was clarified.

Section 5.1.2.2: Verbiage regarding advanced technology techniques was clarified.

Section 6.1.2.5: Verbiage regarding advanced technology techniques was clarified.

Section 10.3.4: Contact information for LDS Hospital was updated.

An updated protocol is available (no password required) on the RTOG Web site, www.rtog.org.




SUMMARY OF CHANGES
Amendment #2 Version Date: October 11, 2005

RTOG 0232, "A Phase III Study Comparing Combined External Beam Radiation and Transperineal Interstitial Permanent Brachytherapy With Brachytherapy Alone for Selected Patients With Intermediate Risk Prostatic Carcinoma"

Study Chair: Bradley R. Prestidge, M.D., (210) 247-0888, bprestidge@texascancerclinic.com


RTOG 0232 has been amended as follows:

Title page:
Index:
Eligibility checklist:
Section 3.1.6: Instructions have been added for patients treated with 5-alpha reductase inhibitors.

Section 4.4: Instructions have been added for volumetric estimates as the last sentence in the section.

Section 4.10: The Utilization of Sexual Medications/Devices has been added to the protocol.

Section 5.1: A heading for pre-registration requirements has been added created for increased clarity.

Section 5.1.1: This section has been renumbered from Section 5.1 due to the addition of the pre-registration requirements heading, as described above. In addition, this section has been given the heading brachytherapy to distinguish from pre-registration requirements for IMRT.

Section 5.1.1.1: This section has been renumbered from Section 5.1.1 due to the addition of the pre-registration requirements heading, as described above.

Sections 5.1.2, 5.1.2.1, and 5.1.2.2: These sections have been added as pre-registration requirements for IMRT use due to the addition of IMRT to the protocol.

Sections 5.1.3: This section has been renumbered from Section 5.2 due to the addition of the sections described above.

Section 5.2: Registration procedures were renumbered from Section 5.3 due to the reorganization of all of Section 5, and the text was modified to reflect mandatory web-based registration.

Sections 6.1: The word "not" was removed from the parenthetical portion of the heading, due to the addition of IMRT to the protocol.

Section 6.1.1: A heading for non-IMRT external beam radiotherapy has been added for increased clarity, due to the addition of IMRT to the protocol.

Section 6.1.1.1: This section has been renumbered from Section 6.1.1 due to the addition of the non-IMRT external beam radiotherapy heading, as described above.

Section 6.1.1.2: This section has been renumbered from Section 6.1.2 due to the addition of the non-IMRT external beam radiotherapy heading, as described above. In addition, the third-to-last sentence and second-to-last sentence were reworded for increased accuracy and now state: "Patients will be treated to a CTV that includes the prostate and seminal vesicles. The PTV is equal to the prostate and seminal vesicles with a minimum 1 cm margin except posteriorly where it may be less."

Section 6.1.1.3: This section has been renumbered from Section 6.1.3 due to the addition of the non-IMRT external beam radiotherapy heading, as described above. In addition, the third sentence was reworded for increased accuracy and now states: "Daily doses will be 1.8 Gy given 5 times per week. The prescribed dose will be defined at the ICRU reference point."

Section 6.1.1.4: This section has been renumbered from Section 6.1.4 due to the addition of the non-IMRT external beam radiotherapy heading, as described above.

Section 6.1.5: This section has been renumbered as Section 6.1.3 due to the reorganization of Section 6 to include guidelines for IMRT use.

Sections 6.1.2, 6.1.2.1, 6.1.2.2, 6.1.2.3, 6.1.2.4, and 6.1.2.5: These sections have been added as guidelines for IMRT use.

Section 6.1.3: This section has been renumbered from Section 6.1.5 due to the reorganization of Section 6 to including guidelines for IMRT use.

Section 11.1

Section 11.2.6: Information about the Utilization of Sexual Medications/Devices has been added to the last sentence of this section.

Section 11.2.6.1: Information about the Utilization of Sexual Medications/Devices has been added as the third sentence of this section.

Section 12.1: The Utilization of Sexual Medications/Devices has been added as a submission requirement (1) within 2 weeks of study entry and (2) at 4, 12, and 24 months post treatment start, then annually for three years.

Section 12.1, * Footnote: Non-IMRT has been added parenthetically at the end of the sentence for increased clarity, due to the addition of IMRT to the protocol.

Section 12.2: For increased clarity, instructions have been added for submitting material to ITC via the ATC website.

Section 12.2.1: A brachytherapy heading has been added created for increased clarity, due to the addition of IMRT to the protocol.

Section 12.2.2: This section has been added due to the addition of IMRT to the protocol.

Sections 12.2.3 and 12.2.4: These sections have been renumbered from Section 12.2.1 and 12.2.2, respectively, due to the reorganization of Section 12, as described above.

Appendix IA

Appendix XI

Appendix XIII, Requirements for RTOG-0232 Site Registration: The first two bullets have been added to detail IMRT registration requirements for sites participating through CTSU.





SUMMARY OF CHANGES
Amendment #1, Version Date: February 15, 2005

RTOG 0232, “A Phase III Study Comparing Combined External Beam Radiation and Transperineal Interstitial Permanent Brachytherapy With Brachytherapy Alone for Selected Patients With Intermediate Risk Prostatic Carcinoma”

Study Chair: Bradley R. Prestidge, M.D., (210) 247-0888, bprestidge@texascancerclinic.com


RTOG 0232 has been amended as follows:

Title page: The contact information for Dr. Prestidge and email address for Dr. Sanda have been updated.

Eligibility checklist: Section 1.1: The third to last sentence of the second paragraph was re-written due to a typographical error. The sentence now reads: “When their analysis was limited to those of patients who received greater than 75.6 Gy, the four-year results reported were 95%, 79% and 60% for the low, intermediate and high risk groups, respectively.”

Section 3.1.1: “NX/” was deleted. “Lymph node evaluation by either CT, MR, or node dissection is required” was added.

Section 3.2.4: “Prior chemotherapy for prostate cancer” has replaced “chemotherapy.”

Section 4.6: “Must” has replaced “can”, so that this section now begins “Lymph node dissection must be performed by one of the following”

Section 6.1: “Protocol treatment must begin within four weeks after study entry” was added for clarity.

Section 6.1.2: The sentence “If targeting is performed from a CT scan and the bladder, urethra and rectum are outlined on the CT scan and displayed on a digitally reconstructed radiograph (DRR), the use of contrast is not required” was added after the second sentence of the section.

Section 6.2.2.2: The second sentence (“The PTV must be defined by the use of a treatment planning CT”) was deleted for increased clarity.

Section 6.2.5.1: This section was added and reads “Assay performed by a third party, such as a third party vendor, is allowed as long as the assay fulfills the requirements in Section 6.2.5.”

Section 6.2.6: The source strengths for Iodine-125 and Palladium-103 were revised for increased clarity. This section of the protocol now states :”For Iodine-125, the allowable source strength for each seed is 0.277 U to .548 U (NIST 99 or later). For Palladium-103 sources, this is 1.29 U to 2.61 U (NIST 99 or later.”

Section 6.4.4: This section was added to provide instructions for reporting of AML/MDS.

Section 10.3.2: For increased clarity: Section 10.3.4: The e-mail associated with LDS Hospital was updated.

Section 11.1 Section 12.0: The mailing address for RTOG Headquarters was updated.

Appendix IA, first bullet: “Or general” was added before “anesthesia,” so that the bullet begins “Local or general anesthesia…”

Appendix IA, Treatment Arms 1 and 2: Appendix IA, Risks Associated with Anesthesia for Seed Implant Therapy: This section was deleted, because these risks should be included on the surgical consent.

Appendix IA, Risks Associated with External Radiation Therapy AND Seed Implant Therapy: Appendix IB, Things to Think About, second paragraph, last sentence: The last part of the sentence was deleted for increased accuracy. The sentence now reads, “Just contact us and let us know that you do not want us to use your tissue, and then any tissue that remains will no longer be used for research.”

Appendix VII, section III, number 2 and 3: The dimensions of the brachytherapy dose calculational grid were changed from “3 mm x 3 mm” to “2 mm x 2 mm.”

Appendix XII: An updated protocol is available (no password required) on the RTOG website: http://www.rtog.org/





SUMMARY OF CHANGES
Update Date: December 16, 2003

RTOG 0232, “A Phase III Study Comparing Combined External Beam Radiation and Transperineal Interstitial Permanent Brachytherapy with Brachytherapy Alone for Selected Patients with Intermediate Risk Prostatic Carcinoma”

Study Chair: Bradley R. Prestidge, M.D. (210) 949-7522 bprestid@saci.org


RTOG 0232 has been updated as follows:

Appendix IA: Under “Why is This Study Being Done?” in the second paragraph, “biomarkers and other” was deleted; under “Brachytherapy” in the first bullet, “Local” was added to anesthesia; under “Whom Do I Call If I Have Questions Or Problems?” CIRB contact information was corrected; and under “Where Can I Get More Information?” the web links were corrected and the section reworded for clarification. These changes were made to make this document consistent with the CIRB approved informed consent document.

NOTE: These are editorial/administrative changes 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: September 10, 2003

RTOG 0232, “A Phase III Study Comparing Combined External Beam Radiation and Transperineal Interstitial Permanent Brachytherapy with Brachytherapy Alone for Selected Patients with Intermediate Risk Prostatic Carcinoma”

Study Chair: Bradley R. Prestidge, M.D. (210) 949-7522 bprestid@saci.org


RTOG 0232 has been updated as follows:

Title Page — Updated Dr. Bice’s phone number to 210-860-1774.

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/