Gynecologic Oncology Group

Gynecologic Oncology GroupUterine Corpus Trials: GCIG

David Scott Miller, M.D., F.A.C.O.G., F.A.C.S.Director and Dallas Foundation Chair in Gynecologic Oncology

Professor of Obstetrics & GynecologyUniversity of Texas Southwestern Medical Center

Dallas, Texas, U.S.A.

Gynecologic Oncology Group

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

Regimen I: •Pelvic Radiation Therapy (4500/25 fractions-5040 cGy/28 fractions) over 5-6 weeks•Optional Vaginal Cuff Boost ONLY for Stage II patients and Stage I patients with papillary serous and clear cell carcinomas

GOG 0249

RANDOMIZE

Eligible:

•Stage I-IIA endometrial carcinoma, with high-intermediate risk factors•Stage IIB (occult) endometrial carcinoma (any histology), with or without risk factors•Stage I-IIB (occult) serous or clear cell endometrial carcinoma, with or without other risk features

Regimen II: •Vaginal Cuff Brachytherapy + 3 cycles of chemotherapy* consisting of: •Paclitaxel 175 mg/m2 (3hr) + Carboplatin AUC 6 q 21 days

*To start within 3 weeks of initiating brachytherapy

Gynecologic Oncology Group

GOG0249

• Objectives– Recurrence free survival– Survival– Patterns of failure– QOL

• Stats– 49% decrease in recurrence/death– 85% > 92% 3 yr RFS– N = 562

• Activated 23 Mar 2009

Gynecologic Oncology Group

Uterine Corpus Committee0184R

• GOG0258 (UC0704): A Randomized Phase III Trial of Cisplatin and Tumor Volume Directed Irradiation Followed by Carboplatin and Paclitaxel vs. Carboplatin and Paclitaxel for Optimally Debulked, Advanced Endometrial Carcinoma

Gynecologic Oncology Group

GOG258

XRT 45GyCisplatin 50mg/m2 D1 and D28

Vaginal brachytherapy

Carboplatin AUC 6Paclitaxel 175mg/m2 q3weeks X4

Surgical debulking; optimalStage III and IVA

Register and randomize

ARM 1 ARM 2

Carboplatin AUC 6Paclitaxel 175mg/m2 q3weeks X6

XRT 45GyCisplatin 50mg/m2 D1 and D28

Vaginal brachytherapy

Carboplatin AUC 6Paclitaxel 175mg/m2 q3weeks X4

Surgical debulking; optimalStage III and IVA

Register and randomize

ARM 1 ARM 2

Carboplatin AUC 6Paclitaxel 175mg/m2 q3weeks X6

Gynecologic Oncology Group

GOG0258

• Objectives– Recurrence free survival– Survival– Adverse effects

• Stats– 28% decrease recurrence/death– 61% > 70% 3 yr RFS– N = 804

Gynecologic Oncology Group

Uterine Corpus Committee Pelvic Recurrence

• 33 + 99 has resulted in:– TAH-BSO lymphadenectomy alone– fewer using adjuvant WPRT

• GOG0238: A Randomized Trial of Pelvic Irradiation With or Without Concurrent Weekly Cisplatin in Patients With Pelvic-Only Recurrence of Carcinoma of the Uterine Corpus

Gynecologic Oncology Group

GOG0238

Gynecologic Oncology Group

GOG0238

• Objectives– PFS– Sites of recurrence– OS

• Stats– Phase II-III– Interim analysis > 60 failures– Opened Feb ‘08– N = 164

Gynecologic Oncology Group

Uterine Corpus Committee150R & 161R

• GOG0261 (UC0701): Randomized Phase III Trial of Carboplatin plus Paclitaxel versus Ifosfamide plus Taxol in Patients with Advanced, Persistent or Recurrent Carcinosarcoma

Gynecologic Oncology Group

GOG0261

• Stage I-IV, Persistent or Recurrent Carcinosarcoma (chemotherapy- naïve)• Patients may have prior pelvic and/or vaginal radiation therapy

Stratification:• History of Pelvic Radiation• Disease Status/ Stage at time of Study registration• Measurable Disease

*Initial dose reduced to Paclitaxel 135 mg/m² and Carboplatin (AUC=5) if prior whole pelvic radiotherapy** Initial dose reduced to Ifosfamide 1.2 g/m²/day x day days if prior whole pelvic radiotherapy*** See Sec. 5.22 for Mesna administration information.

RANDOMIZE

Quality of Life assessments required at: Baseline; approximately week 6 (prior to cycle 3); week 15 (prior to cycle 6); week 26 post initiation of therapy. See section 7.3 for details.

Translational Research requirements include an archival formalin-fixed and paraffin-embedded tumor specimen and a pre-treatment whole blood specimen as described in Section 7.2

REGIMEN I:Paclitaxel 175 mg/m²* IV over 3 hours day 1Carboplatin (AUC=6*) IV day 1Repeat q 3 weeks x6 cycles

G-CSF Support:Filgrastim or Pegfilgrastim beginning day 4-6 (see Section 5.22.)

REGIMEN II:Ifosfamide 1.6 g/m²** IV days 1, 2, 3 Mesna***Paclitaxel 135 mg/m² by 3 hour infusion on day 1Repeat q 3 weeks x6 cycles

Gynecologic Oncology Group

GOG261

• Objectives– OS– PFS– Toxicity– QOL

• Stats– Noninferiority– Death rate < 11%– N = 415, (264 deaths)

Gynecologic Oncology Group

Concept

Biweekly dactinomycin now needs to be tested against 8-day MTX/FAR, arguably the most commonly used regimen worldwide. The 8-day regimen has a similar primary response but a vastly different cost, resource and utility profile, and it has never been subjected to the scrutiny of a multi-centred RCT.