Summary of US Cooperative Group Clinical Brachytherapy Trials

(As of July 11, 2011)

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
Sample size: 586; patients accrued: 553. In 2008, the primary endpoint was changed to freedom from progression, which enabled reducing the sample size considerably. This trial includes comprehensive QA, and the PIs report that the quality of submissions is high.

RTOG 0413:
A Randomized Phase III Study of Conventional Whole Breast Irradiation (WBI) versus Partial Breast Irradiation (PBI) for Women with Stage 0, I, or II Breast Cancer.
Original sample size: 3000. Accrual targets for two low-risk groups was reached sooner than expected so accrual for these groups has been closed, to maintain balance. Sample size has been increased to 4300. Patients accrued: 3929. Very strict QA requirements, including rapid reviews. The quality of submissions is very high.

RTOG 0417:
A Phase II Study of Bevacizumab in Combination with Definitive Radiotherapy and Cisplatin Chemotherapy in Untreated Patients with Locally Advanced Cervical Carcinoma
CLOSED

RTOG 0418:
A Phase II Study of Intensity Modulated Radiation Therapy (IMRT) to the Pelvis +/- Chemotherapy for Post-operative Patients with either Endometrial or Cervical Carcinoma
CLOSED

RTOG 0526:
A Prospective Phase II Trial of Transperineal Ultrasound-Guided Brachytherapy for Locally Recurrent Prostate Adenocarcinoma Following External Beam Radiotherapy
Sample size: 96; patients enrolled: 53. All patients to receive prostate brachytherapy with either iodine (140 Gy) or palladium (120 Gy). As with other seed brachytherapy protocols, credentialing is required.

RTOG 0612:
Investigating Markers of Radiation Outcome in Patients with Intermediate-Risk Prostate Cancer Using DNA Microarray Analysis: An RTOG Pilot Study
Not actually a brachytherapy protocol. This study looks at tumor markers in tissue samples from patients enrolled in RTOG 0232.

RTOG 0630:
A Phase II Trial of Image Guided Preoperative Radiotherapy for Primary Soft Tissue Sarcomas of the Extremity
CLOSED

RTOG 0724:
Phase III Randomized Study of Concurrent Chemotherapy and Pelvic Radiation Therapy With or Without Adjuwant Chemotherapy in High-Risk Patients with Early-Stage Cervical Carcinoma Following Radical Hysterectomy
This is a joint protocol with the GOG. High-risk patients with cervical carcinoma will be randomized into two arms, both of which allow (but don’t require) brachytherapy. Sample size: 400; patients enrolled: 14.

RTOG 0815:
Phase III Prospective Randomized Trial of Dose-Escalated Radiotherapy With or Without Short-Term Androgen Deprivation Therapy for Patients with Intermediate-Risk Prostate Cancer
Primary objective is to demonstrate overall survival advantage of androgen deprivation therapy. Sample size: 1520; patients enrolled: 269.

RTOG 0831:
A Randomized, double-blinded, placebo-controlled phase III trial to evaluate the effectiveness of a phosphodiesterase 5 inhibitor, Tadalafil, in prevention of erectile dysfunction in patients treated with radiotherapy for prostate cancer (PEDS).
Sample size: 218; patients enrolled: 56. Enrollment was suspended between February and September 2010 due to the unavailability of the drug.

RTOG 1021 [ACOSOG Z4099]:
A randomized phase III study of sublobar resection (+/- brachytherapy) versus stereotactic body radiation therapy in high risk patients with stage I non-small cell lung cancer.
This study just opened in May 2011.

RTOG Proposals in development:

RTOG 0924:
Androgen deprivation therapy and high dose radiotherapy with or without whole-pelvic radiotherapy in unfavorable intermediate or favorable high risk prostate cancer: a phase III randomized trial.
The enrollment is 3000 and the goal is to open the trial in the next few months. Brachytherapy will be allowed for a boost.

GOG trials

GOG 9913
GOG 9918
GOG 0238:
A Randomized Trial of Pelvic Irradiation With or Without Concurrent Weekly Cisplatin in Patients with Pelvic-Only Recurrence of Carcinoma of the Uterine Corpus
Calls for 45 Gy ± Cisplatin followed by a boost using either interstitial or intracavitary brachytherapy, or conformal external beam therapy (IMRT is allowed). Sample size: 164; patients enrolled: 26.

GOG-0249:
A Phase III Trial of Pelvic Radiation Therapy Versus Vaginal Cuff Brachytherapy Followed by Paclitaxel/Carboplatin Chemotherapy in Patients with High Risk, Early Stage Endometrial Carcinoma
Sample size: 562; patients enrolled: 175. To determine if treatment with vaginal cuff brachytherapy followed by three cycles of chemotherapy reduces the rate of recurrence or death (i.e. increases recurrence-free survival) when compared to pelvic radiation therapy.

GOG 258:
A Randomized Phase III Trial of Cisplatin, Doxorubicin and Paclitaxel (TAP) Versus Cisplatin, Doxorubicin and Paclitaxel and Tumor Volume Directed Irradiation for Optimally Debulked, Advanced Endometrial Carcinoma
Patients will be randomized to either chemotherapy or chemotherapy followed by “volume-directed radiotherapy�, which seems to mean conformal therapy, possibly by IMRT or brachytherapy.

GOG Proposals in Review:

UC 0604:
Phase III Trial of Pelvic Radiation Therapy Versus Vaginal Cuff Brachytherapy Followed by Paclitaxel/Carboplatin Chemotherapy in Patients with High Risk, Early Stage Endometrial Cancer
Patients will be randomized to
Regimen I: Pelvic Radiation Therapy (4500/25 fxs-5040 cGy/28 fxs) over 5-6 weeks
Optional Vaginal Cuff Boost ONLY for Stage II patients and Stage I patients with papillary serous and clear cell carcinomas, or
Regimen II: Vaginal Cuff Brachytherapy + 3 cycles of chemotherapy, Paclitaxel 175 mg/m2 (3hr) + Carboplatin AUC 6 q 21 days X 3

CVM 0804:
Randomized Phase II study of radiation in combination with either Cetuximab single agent or Cetuximab and cisplatin for patients with newly diagnosed cervical cancer with negative paraaortic nodes
Probably will allow "standard" radiation therapy.

Prepared by:
Geoffrey S. Ibbott, Ph.D.
For the Brachytherapy SubCommittee
July 11, 2011