Clinical trial NCT00011986: Combination Chemotherapy in Treating Patients With Stage III or Stage IV Ovarian Epithelial Cancer or Primary Peritoneal Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Peritoneal Carcinoma
Stage III Ovarian Cancer
Stage IV Ovarian Cancer
Lead sponsor: GOG Foundation
Sponsor class: NETWORK
Collaborators: name: SWOG Cancer Research Network
name: Medical Research Council
name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 4312
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Overall Survival
timeFrame: Up to 9 years
measure: Progression-free Survival
timeFrame: From the date of enrollment to first progression or death or last contact, if alive and progression free.
Secondary outcomes:
measure: Number of Participants With Observed Adverse Effects (Grade 3 and Above) Assessed by Common Toxicity Criteria Version 2.0
timeFrame: Up to 9 years
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Gynecologic Oncology Group
state: Pennsylvania
Study officials:
affiliation: Gynecologic Oncology Group
name: Michael Bookman
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.