Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy in Treating Patients With Stage III or Stage IV Ovarian Epithelial Cancer or Primary Peritoneal Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	Any age	NCI	GOG-0182 SWOG-G0182, MRC-ICON5, ECOG-G0182, NCT00011986, ISRCTN41636183

Objectives

1. Compare the efficacy of paclitaxel and carboplatin with or without gemcitabine, doxorubicin HCl liposome, or topotecan, in terms of overall and progression-free survival, in patients with stage III or IV ovarian epithelial or serous primary peritoneal carcinoma.
2. Determine the response rate in patients with measurable disease treated with these regimens.
3. Compare the toxic effects of these regimens in these patients.
4. Compare the complications in patients treated with these regimens.
5. Determine the dose-intensity and cumulative dose delivery for these regimens in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed stage III or IV ovarian epithelial or serous primary peritoneal carcinoma



• The following are ineligible:
  • Germ cell tumors
  • Sex cord-stromal tumors
  • Carcinosarcomas
  • Mixed Mullerian tumors or carcinosarcomas
  • Metastatic carcinomas from other sites to the ovary
  • Low malignant potential tumors, including micropapillary serous carcinomas
  • Mucinous primary peritoneal carcinoma



• Prior ovarian low malignant potential tumor (borderline carcinoma) that was surgically resected with subsequent development of invasive adenocarcinoma allowed if no prior chemotherapy



• Optimal (no greater than 1 cm) or suboptimal residual disease after initial surgery



• Prior breast cancer allowed provided the following are true:
  • Disease-free for more than 5 years
  • No prior cytotoxic chemotherapy for breast cancer



• Prior or concurrent primary endometrial cancer allowed if the following conditions are met:
  • Stage no greater than IB
  • Less than 3 mm invasion without vascular or lymphatic invasion
  • No poorly differentiated subtypes, including papillary serous, clear cell, or other FIGO grade 3 lesions

Prior/Concurrent Therapy:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• Prior chemotherapy for cancer involving the abdominal cavity or pelvis allowed provided the following are true:
  • More than 3 years since prior therapy
  • No evidence of recurrent disease

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy to any portion of the abdominal cavity or pelvis
• Prior radiotherapy for localized breast, head and neck, or skin cancer allowed provided the following are true:
  • More than 3 years since prior therapy
  • No evidence of recurrent disease

Surgery:

• See Disease Characteristics
• No more than 12 weeks since prior surgical resection

Patient Characteristics:

Age:

• Any age

Performance status:

• GOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST no greater than 2.5 times ULN
• Alkaline phosphatase no greater than 2.5 times ULN
• No acute hepatitis

Renal:

• Creatinine no greater than 1.5 times ULN

Cardiovascular:

• No unstable angina
• No myocardial infarction within the past 6 months
• No evidence of abnormal cardiac conduction (e.g., bundle branch block, heart block) unless stable for the past 6 months

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No greater than grade 1 sensory or motor neuropathy
• No active infection that requires antibiotics
• No other invasive malignancy within the past 5 years except nonmelanoma skin cancer
• No severe or ongoing gastrointestinal bleeding that requires blood product support

Expected Enrollment

Approximately 4,000-5,000 patients (800-1,000 per treatment arm) will be accrued for this study within 3.5-5 years.

Outline

This is a randomized, multicenter study. Patients are stratified into 1 of 3 strata according to extent of residual disease and plans for interval cytoreductive surgery:

• Stratum A: Optimal (microscopic or macroscopic) residual disease without plans for surgery



• Stratum B: Suboptimal residual disease without plans for surgery



• Stratum C: Suboptimal residual disease with plans for surgery

Patients are randomized to 1 of 5 treatment arms.

• Arm I: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment continues every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.



• Arm II: Patients receive chemotherapy as in arm I and gemcitabine IV over 30 minutes on days 1 and 8. Treatment continues as in arm I.



• Arm III: Patients receive chemotherapy as in arm I during courses 1-8 and doxorubicin HCl liposome IV over 1 hour on day 1 during courses 1, 3, 5, and 7. Treatment continues as in arm I.



• Arm IV: Patients receive topotecan IV over 30 minutes on days 1-3 and carboplatin IV over 30 minutes on day 3. Treatment continues every 3 weeks for 4 courses. Patients then receive 4 courses of arm I chemotherapy.



• Arm V: Patients receive gemcitabine IV over 30 minutes on days 1 and 8 and carboplatin IV over 30 minutes on day 8. Treatment continues every 3 weeks for 4 courses. Patients then receive 4 courses of arm I chemotherapy.

Patients with initial unresectable or suboptimal residual disease (more than 1 cm) may undergo interval cytoreductive surgery between courses 4 and 5 of chemotherapy.

Patients are followed every 3 months for 2 years and then every 6 months.

Bookman MA: GOG0182-ICON5: 5-arm phase III randomized trial of paclitaxel (P) and carboplatin (C) vs combinations with gemcitabine (G), PEG-lipososomal doxorubicin (D), or topotecan (T) in patients (pts) with advanced-stage epithelial ovarian (EOC) or primary peritoneal (PPC) carcinoma. [Abstract] J Clin Oncol 24 (Suppl 18): A-5002, 256s, 2006.

Bookman MA, Brady MF, McGuire WP, et al.: Evaluation of new platinum-based treatment regimens in advanced-stage ovarian cancer: a Phase III Trial of the Gynecologic Cancer Intergroup. J Clin Oncol 27 (9): 1419-25, 2009.[PUBMED Abstract]

Bookman MA, Greer BE, Ozols RF: Optimal therapy of advanced ovarian cancer: carboplatin and paclitaxel vs. cisplatin and paclitaxel (GOG 158) and an update on GOG0 182-ICON5. Int J Gynecol Cancer 13 (6): 735-40, 2003 Nov-Dec.[PUBMED Abstract]

Copeland LJ, Bookman M, Trimble E, et al.: Clinical trials of newer regimens for treating ovarian cancer: the rationale for Gynecologic Oncology Group Protocol GOG 182-ICON5. Gynecol Oncol 90 (2 Pt 2): S1-7, 2003.[PUBMED Abstract]

Krivak TC, Darcy KM, Tian C, et al.: Relationship between ERCC1 polymorphisms, disease progression, and survivalin GOG0182, a Gynecologic Oncology Group phase III trial of platinum-based chemotherapy in women with advanced stage epithelial ovarian or primary peritoneal cancer. [Abstract] J Clin Oncol 26 (Suppl 15): A-5540, 2008.

Baysal BE, DeLoia JA, Willett-Brozick JE, et al.: Analysis of CHEK2 gene for ovarian cancer susceptibility. Gynecol Oncol 95 (1): 62-9, 2004.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Gynecologic Oncology Group

Michael Bookman, MD, Protocol chair		Ph: 215-728-2987; 888-369-2427 Email: ma_bookman@fccc.edu
William McGuire, MD, Protocol co-chair		Ph: 443-777-7826; 877-715-4673

Southwest Oncology Group

Amy Tiersten, MD, Protocol chair(Contact information may not be current)		Ph: 212-305-0170

Medical Research Council Clinical Trials Unit

Helen Pearce, PhD, Protocol chair		Ph: 44-207670-4804 Email: hpe@ctu.mrc.ac.uk

Registry Information
Official Title		A Phase III Randomized Trial Of Paclitaxel And Carboplatin Versus Triplet Or Sequential Doublet Combinations In Patients With Epithelial Ovarian Or Primary Peritoneal Carcinoma
Trial Start Date		2001-01-29
Registered in ClinicalTrials.gov		NCT00011986
Date Submitted to PDQ		2001-01-03
Information Last Verified		2004-09-09
NCI Grant/Contract Number		CA27469