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

NCT ID: NCT00011986

Last Updated: 2019-04-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 4312 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-01-31
• Study Completion Date: 2013-01-28

Brief Summary

Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which combination chemotherapy regimen is most effective in treating ovarian epithelial cancer and peritoneal cancer. Randomized phase III trial to compare the effectiveness of various combination chemotherapy regimens in treating patients who have stage III or stage IV ovarian cancer or primary peritoneal cancer.

Detailed Description

OBJECTIVES:

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.

Determine the response rate in patients with measurable disease treated with these regimens.

Compare the toxic effects of these regimens in these patients. Compare the complications in patients treated with these regimens. Determine the dose-intensity and cumulative dose delivery for these regimens in these patients.

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 surgeryPatients 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.

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

Conditions

Primary Peritoneal Carcinoma; Stage III Ovarian Cancer; Stage IV Ovarian Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Paclitaxel

Intervention Type: DRUG

Given IV

Carboplatin

Intervention Type: DRUG

Given IV

Arm II

Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and gemcitabine IV over 30 minutes on days 1 and 8.

Group Type: EXPERIMENTAL

Paclitaxel

Intervention Type: DRUG

Given IV

Carboplatin

Intervention Type: DRUG

Given IV

Gemcitabine Hydrochloride

Intervention Type: DRUG

Given IV

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.

Group Type: EXPERIMENTAL

Paclitaxel

Intervention Type: DRUG

Given IV

Carboplatin

Intervention Type: DRUG

Given IV

Pegylated Liposomal Doxorubicin Hydrochloride

Intervention Type: DRUG

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.

Group Type: EXPERIMENTAL

Paclitaxel

Intervention Type: DRUG

Given IV

Carboplatin

Intervention Type: DRUG

Given IV

Topotecan Hydrochloride

Intervention Type: DRUG

Given IV

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.

Group Type: EXPERIMENTAL

Paclitaxel

Intervention Type: DRUG

Given IV

Carboplatin

Intervention Type: DRUG

Given IV

Gemcitabine Hydrochloride

Intervention Type: DRUG

Given IV

Therapeutic Conventional Surgery

Intervention Type: PROCEDURE

Undergo surgery

Interventions

Paclitaxel

Given IV

Intervention Type: DRUG

Carboplatin

Given IV

Intervention Type: DRUG

Gemcitabine Hydrochloride

Given IV

Intervention Type: DRUG

Pegylated Liposomal Doxorubicin Hydrochloride

Intervention Type: DRUG

Topotecan Hydrochloride

Given IV

Intervention Type: DRUG

Therapeutic Conventional Surgery

Undergo surgery

Intervention Type: PROCEDURE

Other Intervention Names

Anzatax; TAX; dFdC; dFdCyd; doxorubicin HCl liposome; TLC D-99; Hycamtin; SKF S-104864-A; TOPO

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed stage III or IV ovarian epithelial or serous primaryperitoneal carcinoma
• The following are ineligible:

• Germ cell tumors
• Sex cord-stromal tumors
• Carcinosarcomas
• Mixed Mullerian tumors or carcinosarcomas
• Metastatic carcinomas from other sites to theovary
• Low malignant potential tumors, including micropapillary serouscarcinomas
• 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
• Performance status - GOG 0-2
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• 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
• Creatinine no greater than 1.5 times ULN
• 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
• 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
• 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
• 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
• See Disease Characteristics
• No more than 12 weeks since prior surgical resection

• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

SWOG Cancer Research Network

NETWORK

Sponsor Role: collaborator

Medical Research Council

OTHER_GOV

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Gynecologic Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Bookman

Role: PRINCIPAL_INVESTIGATOR

Gynecologic Oncology Group

Locations

Gynecologic Oncology Group

Philadelphia, Pennsylvania, United States

Countries

United States

References

Praiss AM, Miller A, Smith J, Lichtman SM, Bookman M, Aghajanian C, Sabbatini P, Backes F, Cohn DE, Argenta P, Friedlander M, Goodheart MJ, Mutch DG, Gershenson DM, Tewari KS, Wenham RM, Wahner Hendrickson AE, Lee RB, Gray H, Secord AA, Van Le L, O'Cearbhaill RE. Carboplatin dosing in the treatment of ovarian cancer: An NRG oncology group study. Gynecol Oncol. 2023 Jul;174:213-223. doi: 10.1016/j.ygyno.2023.05.013. Epub 2023 May 23.

Reference Type: DERIVED

PMID: 37229879 (View on PubMed)

Sia TY, Tew WP, Purdy C, Chi DS, Menzin AW, Lovecchio JL, Bookman MA, Cohn DE, Teoh DG, Friedlander M, Bender D, Mutch DG, Gershenson DM, Tewari KS, Wenham RM, Wahner Hendrickson AE, Lee RB, Gray HJ, Secord AA, Van Le L, Lichtman SM. The effect of older age on treatment outcomes in women with advanced ovarian cancer receiving chemotherapy: An NRG-Oncology/Gynecologic Oncology Group (GOG-0182-ICON5) ancillary study. Gynecol Oncol. 2023 Jun;173:130-137. doi: 10.1016/j.ygyno.2023.03.018. Epub 2023 May 4.

Reference Type: DERIVED

PMID: 37148580 (View on PubMed)

Rose PG, Java JJ, Salani R, Geller MA, Secord AA, Tewari KS, Bender DP, Mutch DG, Friedlander ML, Van Le L, Method MW, Hamilton CA, Lee RB, Wenham RM, Guntupalli SR, Markman M, Muggia FM, Armstrong DK, Bookman MA, Burger RA, Copeland LJ. Nomogram for Predicting Individual Survival After Recurrence of Advanced-Stage, High-Grade Ovarian Carcinoma. Obstet Gynecol. 2019 Feb;133(2):245-254. doi: 10.1097/AOG.0000000000003086.

Reference Type: DERIVED

PMID: 30633128 (View on PubMed)

Han MK, Tayob N, Murray S, Dransfield MT, Washko G, Scanlon PD, Criner GJ, Casaburi R, Connett J, Lazarus SC, Albert R, Woodruff P, Martinez FJ. Predictors of chronic obstructive pulmonary disease exacerbation reduction in response to daily azithromycin therapy. Am J Respir Crit Care Med. 2014 Jun 15;189(12):1503-8. doi: 10.1164/rccm.201402-0207OC.

Reference Type: DERIVED

PMID: 24779680 (View on PubMed)

Nickles Fader A, Java J, Ueda S, Bristow RE, Armstrong DK, Bookman MA, Gershenson DM; Gynecologic Oncology Group (GOG)*. Survival in women with grade 1 serous ovarian carcinoma. Obstet Gynecol. 2013 Aug;122(2 Pt 1):225-232. doi: 10.1097/AOG.0b013e31829ce7ec.

Reference Type: DERIVED

PMID: 23969788 (View on PubMed)

Other Identifiers

NCI-2012-02376

Identifier Type: REGISTRY

Identifier Source: secondary_id

SWOG-G0182

Identifier Type: -

Identifier Source: secondary_id

CDR0000068467

Identifier Type: -

Identifier Source: secondary_id

ISRCTN41636183

Identifier Type: -

Identifier Source: secondary_id

MRC-ICON5

Identifier Type: -

Identifier Source: secondary_id

ECOG-G0182

Identifier Type: -

Identifier Source: secondary_id

GOG-0182

Identifier Type: OTHER

Identifier Source: secondary_id

GOG-0182

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA027469

Identifier Type: NIH

Identifier Source: secondary_id

View Link

GOG-0182

Identifier Type: -

Identifier Source: org_study_id