gog update - david miller

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.


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


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


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


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


XRT 45GyCisplatin 50mg/m2 D1 and D28

Vaginal brachytherapy


Surgical debulking; optimalStage III and IVA

Register and randomize

ARM 1 ARM 2



GOG0258

• Objectives– Recurrence free survival– Survival– Adverse effects

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


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


GOG0238


GOG0238

• Objectives– PFS– Sites of recurrence– OS

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


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


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


GOG261

• Objectives– OS– PFS– Toxicity– QOL

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


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.

gog update - david miller

Documents

trial of carboplatin

trial of cisplatin

randomized phase

recurrence of carcinoma

yr rfs n

gy cisplatin 50mgm2

vaginal cuff brachytherapy

r gog0258 uc0704