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

• Sponsor: Gynecologic Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00011986
• Collaborator: Southwest Oncology Group (Other), Medical Research Council (Other), National Cancer Institute (NCI) (NIH)
• Enrollment: 4,312
• Location: 1
• Arms: 5
• Duration (Months): 144.9
• Patients Per Site Per Month: 29.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Primary Peritoneal Carcinoma; Stage III Ovarian Cancer; Stage IV Ovarian Cancer	Drug: Paclitaxel; Drug: Carboplatin; Drug: Gemcitabine Hydrochloride; Drug: Pegylated Liposomal Doxorubicin Hydrochloride; Drug: Topotecan Hydrochloride; Procedure: Therapeutic Conventional Surgery	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 4312 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: Jan 1, 2001
• Actual Primary Completion Date: Mar 1, 2010
• Actual Study Completion Date: Jan 28, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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.	Drug: Paclitaxel; Given IV; Other Names: Anzatax TAX ; Drug: Carboplatin; Given IV
Experimental: 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.	Drug: Paclitaxel; Given IV; Other Names: Anzatax TAX ; Drug: Carboplatin; Given IV; Drug: Gemcitabine Hydrochloride; Given IV; Other Names: dFdC dFdCyd
Experimental: 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.	Drug: Paclitaxel; Given IV; Other Names: Anzatax TAX ; Drug: Carboplatin; Given IV; Drug: Pegylated Liposomal Doxorubicin Hydrochloride; Other Names: doxorubicin HCl liposome TLC D-99
Experimental: 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.	Drug: Paclitaxel; Given IV; Other Names: Anzatax TAX ; Drug: Carboplatin; Given IV; Drug: Topotecan Hydrochloride; Given IV; Other Names: Hycamtin SKF S-104864-A TOPO
Experimental: 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.	Drug: Paclitaxel; Given IV; Other Names: Anzatax TAX ; Drug: Carboplatin; Given IV; Drug: Gemcitabine Hydrochloride; Given IV; Other Names: dFdC dFdCyd ; Procedure: Therapeutic Conventional Surgery; Undergo surgery

Outcome Measures

Primary Outcome Measures

1. Overall Survival [Up to 9 years]

   Proportion of participants whose overall survival exceeded 5 years.

2. Progression-free Survival [From the date of enrollment to first progression or death or last contact, if alive and progression free.]

   Median duration in months of progression free survival.

Secondary Outcome Measures

1. Number of Participants With Observed Adverse Effects (Grade 3 and Above) Assessed by Common Toxicity Criteria Version 2.0 [Up to 9 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Gynecologic Oncology Group	Philadelphia	Pennsylvania	United States	19103

Sponsors and Collaborators

• Gynecologic Oncology Group
• Southwest Oncology Group
• Medical Research Council
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Michael Bookman, Gynecologic Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gynecologic Oncology Group
• ClinicalTrials.gov Identifier: NCT00011986
• Other Study ID Numbers: GOG-0182; NCI-2012-02376; SWOG-G0182; CDR0000068467; ISRCTN41636183; MRC-ICON5; ECOG-G0182; GOG-0182; GOG-0182; U10CA027469
• First Posted: Jan 27, 2003
• Last Update Posted: Apr 16, 2019
• Last Verified: Mar 1, 2016

• Additional relevant MeSH terms: Carcinoma; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Gemcitabine; Paclitaxel; Carboplatin; Doxorubicin; Liposomal doxorubicin; Topotecan

Study Results

Participant Flow

Recruitment Details	Received began 1/29/2001 and ended 1/28/2003. This was an interventional trial involving patients enrolled from the United States (US), Canada, United Kingdom (UK), Italy, Australia, and New Zealand.
Pre-assignment Detail	This study involved patients enrolled from two cooperative groups with the plan to combine data. 3882 patients were enrolled from one cooperative group and 430 from the other. This report includes those patients from both groups.

Arm/Group Title	Carbo/Taxol	Carbo/Taxol/Gemcitabine	Carbo/Taxol/Doxil	Carbo/Topotecan - Carbo/Taxol	Carbo/Gemcitabine - Carbo/Taxol
Arm/Group Description	Carboplatin AUC 6 IV on day 1 plus Paclitaxel 175 mg/m2 IV on day 1 x 8 cycles	Carboplatin AUC 5 IV on day 1 plus Paclitaxel 175 mg/m2 IV on day 1 x 8 cycles plus Gemcitabine 800 mg/m2/dIV on days 1 and 8 x 8 cycles	Carboplatin AUC 5 IV on day 1 plus Paclitaxel 175 mg/m2 IV on day 1 x 8 cycles plus Doxil 30 mg/m2 IV every other cycle on day 1 x 8 cycles	Topotecan 1.25 mg/m2/dIV days 1-3 plus Carboplatin AUC 5 IV on day 3 plus x 4 cycles followed by Carboplatin AUC 6 IV on day 1 plus Paclitaxel 175 mg/m2 IV on day 1 x 4 cycles	Gemcitabine 1000 mg/m2/dIV on days 1 and 8 plus Carboplatin AUC 6 IV on day 8 plus x 4 cycles followed by Carboplatin AUC 6 IV on day 1 plus Paclitaxel 175 mg/m2 IV on day 1 x 4 cycles
Period Title: Overall Study
STARTED	864	864	862	861	861
Initiated Treatment	862	860	854	846	851
COMPLETED	864	864	862	861	861
NOT COMPLETED	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Carbo/Taxol	Carbo/Taxol/Gemcitabine	Carbo/Taxol/Doxil	Carbo/Topotecan - Carbo/Taxol	Carbo/Gemcitabine - Carbo/Taxol	Total
Arm/Group Description	Carboplatin AUC 6 IV on day 1 plus Paclitaxel 175 mg/m2 IV on day 1 x 8 cycles	Carboplatin AUC 5 IV on day 1 plus Paclitaxel 175 mg/m2 IV on day 1 x 8 cycles plus Gemcitabine 800 mg/m2/dIV on days 1 and 8 x 8 cycles	Carboplatin AUC 5 IV on day 1 plus Paclitaxel 175 mg/m2 IV on day 1 x 8 cycles plus Doxil 30 mg/m2 IV every other cycle on day 1 x 8 cycles	Topotecan 1.25 mg/m2/dIV days 1-3 plus Carboplatin AUC 5 IV on day 3 plus x 4 cycles followed by Carboplatin AUC 6 IV on day 1 plus Paclitaxel 175 mg/m2 IV on day 1 x 4 cycles	Gemcitabine 1000 mg/m2/dIV on days 1 and 8 plus Carboplatin AUC 6 IV on day 8 plus x 4 cycles followed by Carboplatin AUC 6 IV on day 1 plus Paclitaxel 175 mg/m2 IV on day 1 x 4 cycles	Total of all reporting groups
Overall Participants	864	864	862	861	861	4312
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.8 (11.1)	58.8 (10.8)	59.0 (11.1)	58.2 (11.0)	58.9 (10.7)	58.6 (10.9)
Sex: Female, Male (Count of Participants)
Female	864 100%	864 100%	862 100%	861 100%	861 100%	4312 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
International Federation of Gynecology and Obstetrics (FIGO) Stage (participants) [Number]
Stage III:see description for details	724 83.8%	749 86.7%	743 86.2%	744 86.4%	721 83.7%	3681 85.4%
Stage IV:see description for details	140 16.2%	115 13.3%	119 13.8%	117 13.6%	140 16.3%	631 14.6%
Primary Site of Disease (participants) [Number]
Ovary	748 86.6%	752 87%	737 85.5%	752 87.3%	751 87.2%	3740 86.7%
Peritoneum	116 13.4%	112 13%	125 14.5%	109 12.7%	110 12.8%	572 13.3%
Size of Residual Disease (participants) [Number]
Microscopic only	197 22.8%	218 25.2%	206 23.9%	220 25.6%	203 23.6%	1044 24.2%
≤ 1 cm gross disease	404 46.8%	384 44.4%	405 47%	358 41.6%	398 46.2%	1949 45.2%
> 1 cm gross disease	263 30.4%	262 30.3%	251 29.1%	283 32.9%	260 30.2%	1319 30.6%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	Proportion of participants whose overall survival exceeded 5 years.
Time Frame	Up to 9 years

Outcome Measure Data

Analysis Population Description

All enrolled participants.

Arm/Group Title	Carbo/Taxol	Carbo/Taxol/Gemcitabine	Carbo/Taxol/Doxil	Carbo/Topotecan - Carbo/Taxol	Carbo/Gemcitabine - Carbo/Taxol
Arm/Group Description	Carboplatin AUC 6 IV on day 1 plus Paclitaxel 175 mg/m2 IV on day 1 x 8 cycles	Carboplatin AUC 5 IV on day 1 plus Paclitaxel 175 mg/m2 IV on day 1 x 8 cycles plus Gemcitabine 800 mg/m2/dIV on days 1 and 8 x 8 cycles	Carboplatin AUC 5 IV on day 1 plus Paclitaxel 175 mg/m2 IV on day 1 x 8 cycles plus Doxil 30 mg/m2 IV every other cycle on day 1 x 8 cycles	Topotecan 1.25 mg/m2/dIV days 1-3 plus Carboplatin AUC 5 IV on day 3 plus x 4 cycles followed by Carboplatin AUC 6 IV on day 1 plus Paclitaxel 175 mg/m2 IV on day 1 x 4 cycles	Gemcitabine 1000 mg/m2/dIV on days 1 and 8 plus Carboplatin AUC 6 IV on day 8 plus x 4 cycles followed by Carboplatin AUC 6 IV on day 1 plus Paclitaxel 175 mg/m2 IV on day 1 x 4 cycles
Measure Participants	864	864	862	861	861
Number [Proportion of participants]	0.35 0%	0.34 0%	0.39 0%	0.34 0%	0.30 0%

2. Primary Outcome

Title	Progression-free Survival
Description	Median duration in months of progression free survival.
Time Frame	From the date of enrollment to first progression or death or last contact, if alive and progression free.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Carbo/Taxol	Carbo/Taxol/Gemcitabine	Carbo/Taxol/Doxil	Carbo/Topotecan - Carbo/Taxol	Carbo/Gemcitabine - Carbo/Taxol
Arm/Group Description	Carboplatin AUC 6 IV on day 1 plus Paclitaxel 175 mg/m2 IV on day 1 x 8 cycles	Carboplatin AUC 5 IV on day 1 plus Paclitaxel 175 mg/m2 IV on day 1 x 8 cycles plus Gemcitabine 800 mg/m2/dIV on days 1 and 8 x 8 cycles	Carboplatin AUC 5 IV on day 1 plus Paclitaxel 175 mg/m2 IV on day 1 x 8 cycles plus Doxil 30 mg/m2 IV every other cycle on day 1 x 8 cycles	Topotecan 1.25 mg/m2/dIV days 1-3 plus Carboplatin AUC 5 IV on day 3 plus x 4 cycles followed by Carboplatin AUC 6 IV on day 1 plus Paclitaxel 175 mg/m2 IV on day 1 x 4 cycles	Gemcitabine 1000 mg/m2/dIV on days 1 and 8 plus Carboplatin AUC 6 IV on day 8 plus x 4 cycles followed by Carboplatin AUC 6 IV on day 1 plus Paclitaxel 175 mg/m2 IV on day 1 x 4 cycles
Measure Participants	864	864	862	861	861
Median (95% Confidence Interval) [months]	16.0	16.3	16.4	15.4	15.4

3. Secondary Outcome

Title	Number of Participants With Observed Adverse Effects (Grade 3 and Above) Assessed by Common Toxicity Criteria Version 2.0
Time Frame	Up to 9 years

Outcome Measure Data

Analysis Population Description

Eligible and treated participants

Arm/Group Title	Grade 3 and Above on ToxicityCarbo/Taxol	Grade 3 and Above on Carbo/Taxol/Gemcitabine	Grade 3 and Above on Carbo/Taxol/Doxil	Grade 3 and Above on Carbo/Topotecan - Carbo/Taxol	Grade 3 and Above on Carbo/Gemcitabine - Carbo/Taxol
Arm/Group Description	Carboplatin AUC 6 IV on day 1 plus Paclitaxel 175 mg/m2 IV on day 1 x 8 cycles	Carboplatin AUC 5 IV on day 1 plus Paclitaxel 175 mg/m2 IV on day 1 x 8 cycles plus Gemcitabine 800 mg/m2/dIV on days 1 and 8 x 8 cycles	Carboplatin AUC 5 IV on day 1 plus Paclitaxel 175 mg/m2 IV on day 1 x 8 cycles plus Doxil 30 mg/m2 IV every other cycle on day 1 x 8 cycles	Topotecan 1.25 mg/m2/dIV days 1-3 plus Carboplatin AUC 5 IV on day 3 plus x 4 cycles followed by Carboplatin AUC 6 IV on day 1 plus Paclitaxel 175 mg/m2 IV on day 1 x 4 cycles	Gemcitabine 1000 mg/m2/dIV on days 1 and 8 plus Carboplatin AUC 6 IV on day 8 plus x 4 cycles followed by Carboplatin AUC 6 IV on day 1 plus Paclitaxel 175 mg/m2 IV on day 1 x 4 cycles
Measure Participants	862	860	854	846	851
Leukopenia	438 50.7%	686 79.4%	595 69%	476 55.3%	513 59.6%
Neutropenia	749 86.7%	798 92.4%	782 90.7%	779 90.5%	761 88.4%
Thrombocytopenia	193 22.3%	520 60.2%	320 37.1%	303 35.2%	486 56.4%
Anemia	102 11.8%	196 22.7%	160 18.6%	167 19.4%	203 23.6%
Other Hematologic	156 18.1%	338 39.1%	244 28.3%	246 28.6%	315 36.6%
Allergy	38 4.4%	20 2.3%	28 3.2%	21 2.4%	26 3%
Auditory	5 0.6%	2 0.2%	3 0.3%	2 0.2%	1 0.1%
Cardiovascular	20 2.3%	36 4.2%	34 3.9%	17 2%	23 2.7%
Coagulation	5 0.6%	10 1.2%	4 0.5%	9 1%	7 0.8%
Constitutional	54 6.3%	96 11.1%	84 9.7%	73 8.5%	57 6.6%
Dermatologic	13 1.5%	6 0.7%	11 1.3%	6 0.7%	8 0.9%
Endocrine	0 0%	4 0.5%	2 0.2%	1 0.1%	1 0.1%
Gastrointestinal	90 10.4%	145 16.8%	124 14.4%	105 12.2%	92 10.7%
Genitourinary/Renal	9 1%	8 0.9%	13 1.5%	6 0.7%	9 1%
Hemorrhage	8 0.9%	29 3.4%	20 2.3%	8 0.9%	30 3.5%
Hepatic	13 1.5%	32 3.7%	11 1.3%	13 1.5%	25 2.9%
Infection/Fever	76 8.8%	138 16%	134 15.5%	84 9.8%	82 9.5%
Metabolic	61 7.1%	55 6.4%	55 6.4%	37 4.3%	45 5.2%
Musculoskeletal	7 0.8%	18 2.1%	13 1.5%	8 0.9%	10 1.2%
Neurologic	34 3.9%	47 5.4%	43 5%	28 3.3%	35 4.1%
Peripheral Neurologic	45 5.2%	59 6.8%	45 5.2%	35 4.1%	24 2.8%
Ocular/Visual	1 0.1%	3 0.3%	1 0.1%	3 0.3%	3 0.3%
Pain	53 6.1%	75 8.7%	75 8.7%	66 7.7%	52 6%
Pulmonary	19 2.2%	37 4.3%	39 4.5%	21 2.4%	37 4.3%
Sexual	0 0%	0 0%	1 0.1%	1 0.1%	0 0%
Second Primary	34 3.9%	66 7.6%	51 5.9%	41 4.8%	57 6.6%

Adverse Events

Time Frame	From date of enrollment onto the study to 30 days after last treatment cycle or any Adverse Event (AE) considered to be due to study treatment regardless of when it occurred.
Adverse Event Reporting Description	Only Serious Adverse Events(SAE) for the US-enrolled participants is able to be reported. Due to the methods in which AEs were collected &/or stored, it is not possible to report only the Other(not including Serious) AEs in the appropriate table. Therefore that table is a combined set of SAEs & non-serious AEs. Other AEs are Grade 2 or worse.
Arm/Group Title	Carbo/Taxol		Carbo/Taxol/Gemcitabine		Carbo/Taxol/Doxil		Carbo/Topotecan - Carbo/Taxol		Carbo/Gemcitabine - Carbo/Taxol
Arm/Group Description	Carboplatin AUC 6 IV on day 1 plus Paclitaxel 175 mg/m2 IV on day 1 x 8 cycles		Carboplatin AUC 5 IV on day 1 plus Paclitaxel 175 mg/m2 IV on day 1 x 8 cycles plus Gemcitabine 800 mg/m2/dIV on days 1 and 8 x 8 cycles		Carboplatin AUC 5 IV on day 1 plus Paclitaxel 175 mg/m2 IV on day 1 x 8 cycles plus Doxil 30 mg/m2 IV every other cycle on day 1 x 8 cycles		Topotecan 1.25 mg/m2/dIV days 1-3 plus Carboplatin AUC 5 IV on day 3 plus x 4 cycles followed by Carboplatin AUC 6 IV on day 1 plus Paclitaxel 175 mg/m2 IV on day 1 x 4 cycles		Gemcitabine 1000 mg/m2/dIV on days 1 and 8 plus Carboplatin AUC 6 IV on day 8 plus x 4 cycles followed by Carboplatin AUC 6 IV on day 1 plus Paclitaxel 175 mg/m2 IV on day 1 x 4 cycles
All Cause Mortality
	Carbo/Taxol		Carbo/Taxol/Gemcitabine		Carbo/Taxol/Doxil		Carbo/Topotecan - Carbo/Taxol		Carbo/Gemcitabine - Carbo/Taxol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Carbo/Taxol		Carbo/Taxol/Gemcitabine		Carbo/Taxol/Doxil		Carbo/Topotecan - Carbo/Taxol		Carbo/Gemcitabine - Carbo/Taxol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	86/777 (11.1%)		107/774 (13.8%)		115/767 (15%)		77/766 (10.1%)		100/767 (13%)
Blood and lymphatic system disorders
Hemoglobin	2/777 (0.3%)		2/774 (0.3%)		1/767 (0.1%)		0/766 (0%)		3/767 (0.4%)
Platelets	1/777 (0.1%)		12/774 (1.6%)		2/767 (0.3%)		0/766 (0%)		8/767 (1%)
Neutrophils/Granulocytes	1/777 (0.1%)		3/774 (0.4%)		3/767 (0.4%)		3/766 (0.4%)		1/767 (0.1%)
Leukocytes	0/777 (0%)		0/774 (0%)		0/767 (0%)		1/766 (0.1%)		0/767 (0%)
Cardiac disorders
Hypertension	1/777 (0.1%)		0/774 (0%)		0/767 (0%)		1/766 (0.1%)		1/767 (0.1%)
Circulatory Or Cardiac-Other	0/777 (0%)		0/774 (0%)		1/767 (0.1%)		0/766 (0%)		1/767 (0.1%)
Cardiac Left Ventricular Function	0/777 (0%)		1/774 (0.1%)		1/767 (0.1%)		0/766 (0%)		1/767 (0.1%)
Cardiac Troponin I	0/777 (0%)		0/774 (0%)		1/767 (0.1%)		0/766 (0%)		0/767 (0%)
Hypotension	1/777 (0.1%)		0/774 (0%)		0/767 (0%)		0/766 (0%)		0/767 (0%)
Sinus Tachycardia	0/777 (0%)		1/774 (0.1%)		2/767 (0.3%)		0/766 (0%)		0/767 (0%)
Phlebitis	0/777 (0%)		1/774 (0.1%)		0/767 (0%)		0/766 (0%)		1/767 (0.1%)
Vasovagal Episode	0/777 (0%)		1/774 (0.1%)		0/767 (0%)		0/766 (0%)		0/767 (0%)
Supraventricular Arrhythmias	1/777 (0.1%)		1/774 (0.1%)		1/767 (0.1%)		0/766 (0%)		1/767 (0.1%)
Thrombosis/Embolism	10/777 (1.3%)		9/774 (1.2%)		13/767 (1.7%)		13/766 (1.7%)		16/767 (2.1%)
Nodal/Junctional Arrhythmia/Dysrhythmia	0/777 (0%)		0/774 (0%)		1/767 (0.1%)		0/766 (0%)		0/767 (0%)
Arrhythmia- Other	0/777 (0%)		0/774 (0%)		1/767 (0.1%)		0/766 (0%)		2/767 (0.3%)
Cardiac-Ischemia/Infarction	1/777 (0.1%)		1/774 (0.1%)		2/767 (0.3%)		1/766 (0.1%)		0/767 (0%)
Sinus Bradycardia	0/777 (0%)		1/774 (0.1%)		0/767 (0%)		0/766 (0%)		0/767 (0%)
Edema	0/777 (0%)		1/774 (0.1%)		0/767 (0%)		1/766 (0.1%)		1/767 (0.1%)
Ear and labyrinth disorders
Inner Ear/Hearing	0/777 (0%)		0/774 (0%)		0/767 (0%)		0/766 (0%)		1/767 (0.1%)
Hearing-Other	0/777 (0%)		1/774 (0.1%)		0/767 (0%)		0/766 (0%)		0/767 (0%)
Eye disorders
Glaucoma	0/777 (0%)		1/774 (0.1%)		0/767 (0%)		0/766 (0%)		0/767 (0%)
Gastrointestinal disorders
Stomatitis/Pharyngitis	0/777 (0%)		0/774 (0%)		1/767 (0.1%)		0/766 (0%)		1/767 (0.1%)
Pancreatitis	0/777 (0%)		0/774 (0%)		0/767 (0%)		1/766 (0.1%)		0/767 (0%)
Gi-Other	1/777 (0.1%)		1/774 (0.1%)		0/767 (0%)		1/766 (0.1%)		0/767 (0%)
Ileus	5/777 (0.6%)		4/774 (0.5%)		2/767 (0.3%)		4/766 (0.5%)		5/767 (0.7%)
Gastritis	0/777 (0%)		0/774 (0%)		0/767 (0%)		2/766 (0.3%)		0/767 (0%)
Anorexia	0/777 (0%)		0/774 (0%)		0/767 (0%)		0/766 (0%)		1/767 (0.1%)
Dyspepsia/Heartburn	0/777 (0%)		0/774 (0%)		1/767 (0.1%)		1/766 (0.1%)		0/767 (0%)
Gastric Ulcer	1/777 (0.1%)		0/774 (0%)		1/767 (0.1%)		0/766 (0%)		0/767 (0%)
Colitis	0/777 (0%)		1/774 (0.1%)		1/767 (0.1%)		0/766 (0%)		0/767 (0%)
Ascites (Non-Malignant)	0/777 (0%)		1/774 (0.1%)		1/767 (0.1%)		1/766 (0.1%)		1/767 (0.1%)
Fistula-Rectal/Anal	0/777 (0%)		0/774 (0%)		0/767 (0%)		1/766 (0.1%)		0/767 (0%)
Dehydration	2/777 (0.3%)		3/774 (0.4%)		2/767 (0.3%)		2/766 (0.3%)		1/767 (0.1%)
Constipation	6/777 (0.8%)		7/774 (0.9%)		3/767 (0.4%)		5/766 (0.7%)		3/767 (0.4%)
Diarrhea (Without Colostomy)	1/777 (0.1%)		4/774 (0.5%)		3/767 (0.4%)		1/766 (0.1%)		2/767 (0.3%)
Vomiting	7/777 (0.9%)		8/774 (1%)		11/767 (1.4%)		7/766 (0.9%)		1/767 (0.1%)
Nausea	0/777 (0%)		0/774 (0%)		2/767 (0.3%)		1/766 (0.1%)		1/767 (0.1%)
General disorders
Constitutional Symptoms-Other	1/777 (0.1%)		0/774 (0%)		0/767 (0%)		0/766 (0%)		0/767 (0%)
Fever In The Absence Of Neutropenia	0/777 (0%)		0/774 (0%)		0/767 (0%)		1/766 (0.1%)		0/767 (0%)
Fatigue	0/777 (0%)		3/774 (0.4%)		1/767 (0.1%)		1/766 (0.1%)		0/767 (0%)
Chest Pain Non-Cardiac Or Non-Pleuritic	0/777 (0%)		0/774 (0%)		1/767 (0.1%)		1/766 (0.1%)		0/767 (0%)
Headache	0/777 (0%)		0/774 (0%)		1/767 (0.1%)		0/766 (0%)		0/767 (0%)
Abdominal Pain Or Cramping	4/777 (0.5%)		3/774 (0.4%)		4/767 (0.5%)		1/766 (0.1%)		1/767 (0.1%)
Bone Pain	1/777 (0.1%)		0/774 (0%)		0/767 (0%)		0/766 (0%)		0/767 (0%)
Arthralgia	0/777 (0%)		0/774 (0%)		1/767 (0.1%)		0/766 (0%)		0/767 (0%)
Myalgia	1/777 (0.1%)		0/774 (0%)		0/767 (0%)		0/766 (0%)		0/767 (0%)
Pain-Other	0/777 (0%)		1/774 (0.1%)		1/767 (0.1%)		0/766 (0%)		1/767 (0.1%)
Hepatobiliary disorders
Hepatic-Other	0/777 (0%)		0/774 (0%)		0/767 (0%)		1/766 (0.1%)		1/767 (0.1%)
Sgpt	0/777 (0%)		0/774 (0%)		0/767 (0%)		0/766 (0%)		1/767 (0.1%)
Sgot	0/777 (0%)		2/774 (0.3%)		0/767 (0%)		1/766 (0.1%)		1/767 (0.1%)
Bilirubin	0/777 (0%)		0/774 (0%)		1/767 (0.1%)		0/766 (0%)		0/767 (0%)
Immune system disorders
Allergy-Other	4/777 (0.5%)		0/774 (0%)		2/767 (0.3%)		1/766 (0.1%)		0/767 (0%)
Allergic Reaction/Hypersensitivity	9/777 (1.2%)		6/774 (0.8%)		6/767 (0.8%)		3/766 (0.4%)		6/767 (0.8%)
Infections and infestations
Infection, Other	1/777 (0.1%)		1/774 (0.1%)		0/767 (0%)		0/766 (0%)		2/767 (0.3%)
Catheter-Related Infection	0/777 (0%)		1/774 (0.1%)		1/767 (0.1%)		0/766 (0%)		0/767 (0%)
Infection With Unknown Anc	0/777 (0%)		1/774 (0.1%)		1/767 (0.1%)		1/766 (0.1%)		2/767 (0.3%)
Infection Documented W Grd 3/4 Neutropn.	5/777 (0.6%)		9/774 (1.2%)		15/767 (2%)		7/766 (0.9%)		4/767 (0.5%)
Infection Without Neutropenia	7/777 (0.9%)		8/774 (1%)		5/767 (0.7%)		6/766 (0.8%)		6/767 (0.8%)
Febrile Neutropenia-Fuo Infect Not Docum	8/777 (1%)		12/774 (1.6%)		15/767 (2%)		10/766 (1.3%)		7/767 (0.9%)
Metabolism and nutrition disorders
Metabolic-Other	0/777 (0%)		1/774 (0.1%)		0/767 (0%)		1/766 (0.1%)		0/767 (0%)
Hyponatremia	0/777 (0%)		1/774 (0.1%)		0/767 (0%)		1/766 (0.1%)		1/767 (0.1%)
Hyperkalemia	0/777 (0%)		0/774 (0%)		0/767 (0%)		0/766 (0%)		1/767 (0.1%)
Hyperglycemia	0/777 (0%)		0/774 (0%)		0/767 (0%)		1/766 (0.1%)		0/767 (0%)
Hypokalemia	0/777 (0%)		0/774 (0%)		0/767 (0%)		0/766 (0%)		2/767 (0.3%)
Hypomagnesmia	0/777 (0%)		1/774 (0.1%)		0/767 (0%)		0/766 (0%)		0/767 (0%)
Musculoskeletal and connective tissue disorders
Joint, Muscle, Or Bone-Other	0/777 (0%)		0/774 (0%)		1/767 (0.1%)		0/766 (0%)		0/767 (0%)
Nervous system disorders
Tremor	0/777 (0%)		2/774 (0.3%)		0/767 (0%)		0/766 (0%)		0/767 (0%)
Speech Impairment- Dysphasia/Aphasia	0/777 (0%)		0/774 (0%)		1/767 (0.1%)		0/766 (0%)		0/767 (0%)
Seizure(S)	1/777 (0.1%)		0/774 (0%)		0/767 (0%)		0/766 (0%)		2/767 (0.3%)
Hallucinations	0/777 (0%)		0/774 (0%)		0/767 (0%)		0/766 (0%)		1/767 (0.1%)
Cns Cerebrovascular Ischemia	0/777 (0%)		0/774 (0%)		4/767 (0.5%)		0/766 (0%)		2/767 (0.3%)
Confusion	0/777 (0%)		0/774 (0%)		1/767 (0.1%)		1/766 (0.1%)		1/767 (0.1%)
Syncope	6/777 (0.8%)		2/774 (0.3%)		5/767 (0.7%)		0/766 (0%)		3/767 (0.4%)
Mood Alteration-Anxiety Agitation	0/777 (0%)		1/774 (0.1%)		0/767 (0%)		1/766 (0.1%)		0/767 (0%)
Dizziness/Lightheadedness	0/777 (0%)		0/774 (0%)		0/767 (0%)		1/766 (0.1%)		1/767 (0.1%)
Neuropathy-Sensory	1/777 (0.1%)		0/774 (0%)		1/767 (0.1%)		0/766 (0%)		0/767 (0%)
Neuropathy Motor	1/777 (0.1%)		1/774 (0.1%)		1/767 (0.1%)		0/766 (0%)		1/767 (0.1%)
Renal and urinary disorders
Operative Injury To Bladder/Ureter	0/777 (0%)		0/774 (0%)		0/767 (0%)		0/766 (0%)		1/767 (0.1%)
Fistula Or Gu Fistula	0/777 (0%)		0/774 (0%)		2/767 (0.3%)		0/766 (0%)		0/767 (0%)
Renal Failure	0/777 (0%)		0/774 (0%)		2/767 (0.3%)		1/766 (0.1%)		1/767 (0.1%)
Creatinine	1/777 (0.1%)		0/774 (0%)		0/767 (0%)		0/766 (0%)		1/767 (0.1%)
Renal/Gu-Other	0/777 (0%)		0/774 (0%)		0/767 (0%)		0/766 (0%)		1/767 (0.1%)
Respiratory, thoracic and mediastinal disorders
Pleural Effusion (Non-Malignant)	1/777 (0.1%)		2/774 (0.3%)		2/767 (0.3%)		1/766 (0.1%)		3/767 (0.4%)
Dyspnea	1/777 (0.1%)		3/774 (0.4%)		4/767 (0.5%)		3/766 (0.4%)		0/767 (0%)
Pneumothorax	0/777 (0%)		0/774 (0%)		0/767 (0%)		0/766 (0%)		1/767 (0.1%)
Hypoxia	0/777 (0%)		2/774 (0.3%)		0/767 (0%)		0/766 (0%)		0/767 (0%)
Adult Respiratory Distress Syndrome	0/777 (0%)		1/774 (0.1%)		1/767 (0.1%)		0/766 (0%)		1/767 (0.1%)
Skin and subcutaneous tissue disorders
Pruritus	1/777 (0.1%)		0/774 (0%)		0/767 (0%)		0/766 (0%)		0/767 (0%)
Urticaria	0/777 (0%)		0/774 (0%)		1/767 (0.1%)		1/766 (0.1%)		1/767 (0.1%)
Wound-Infectious	1/777 (0.1%)		1/774 (0.1%)		0/767 (0%)		1/766 (0.1%)		2/767 (0.3%)
Rash/Desquamation	0/777 (0%)		1/774 (0.1%)		0/767 (0%)		0/766 (0%)		2/767 (0.3%)
Skin-Other	0/777 (0%)		0/774 (0%)		0/767 (0%)		0/766 (0%)		1/767 (0.1%)
Wound-Non-Infectious	0/777 (0%)		0/774 (0%)		1/767 (0.1%)		0/766 (0%)		0/767 (0%)
Erythema Multiforme	0/777 (0%)		1/774 (0.1%)		0/767 (0%)		0/766 (0%)		0/767 (0%)
Vascular disorders
Hemorrhage-Other	0/777 (0%)		0/774 (0%)		0/767 (0%)		0/766 (0%)		1/767 (0.1%)
Rectal Bleeding/Hematochezia	0/777 (0%)		1/774 (0.1%)		0/767 (0%)		0/766 (0%)		1/767 (0.1%)
Hemorrhage/Bleeding Associated With Surgery	0/777 (0%)		0/774 (0%)		0/767 (0%)		0/766 (0%)		1/767 (0.1%)
Epistaxis	0/777 (0%)		0/774 (0%)		0/767 (0%)		1/766 (0.1%)		1/767 (0.1%)
Hemorrhage/Bleeding With Grade 3 Or 4 Th	0/777 (0%)		0/774 (0%)		1/767 (0.1%)		0/766 (0%)		0/767 (0%)
Hematuria (In The Absence Of Vaginal Bleeding	1/777 (0.1%)		0/774 (0%)		0/767 (0%)		0/766 (0%)		0/767 (0%)
Other (Not Including Serious) Adverse Events
	Carbo/Taxol		Carbo/Taxol/Gemcitabine		Carbo/Taxol/Doxil		Carbo/Topotecan - Carbo/Taxol		Carbo/Gemcitabine - Carbo/Taxol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	857/862 (99.4%)		856/860 (99.5%)		852/854 (99.8%)		843/846 (99.6%)		849/851 (99.8%)
Blood and lymphatic system disorders
Leukopenia	746/862 (86.5%)		826/860 (96%)		806/854 (94.4%)		782/846 (92.4%)		800/851 (94%)
Neutropenia	821/862 (95.2%)		838/860 (97.4%)		818/854 (95.8%)		830/846 (98.1%)		825/851 (96.9%)
Thrombocytopenia	319/862 (37%)		675/860 (78.5%)		438/854 (51.3%)		460/846 (54.4%)		645/851 (75.8%)
Anemia	508/862 (58.9%)		700/860 (81.4%)		603/854 (70.6%)		647/846 (76.5%)		685/851 (80.5%)
Other Hemotologic	164/862 (19%)		351/860 (40.8%)		261/854 (30.6%)		260/846 (30.7%)		327/851 (38.4%)
Hemorrhage	14/862 (1.6%)		41/860 (4.8%)		33/854 (3.9%)		18/846 (2.1%)		50/851 (5.9%)
Cardiac disorders
Cardiovascular	43/862 (5%)		72/860 (8.4%)		62/854 (7.3%)		36/846 (4.3%)		61/851 (7.2%)
Ear and labyrinth disorders
Auditory	22/862 (2.6%)		20/860 (2.3%)		23/854 (2.7%)		17/846 (2%)		15/851 (1.8%)
Endocrine disorders
Endocrine	36/862 (4.2%)		38/860 (4.4%)		41/854 (4.8%)		40/846 (4.7%)		27/851 (3.2%)
Eye disorders
Ocular/Visual	42/862 (4.9%)		54/860 (6.3%)		64/854 (7.5%)		28/846 (3.3%)		38/851 (4.5%)
Gastrointestinal disorders
Gastrointestinal	421/862 (48.8%)		469/860 (54.5%)		496/854 (58.1%)		403/846 (47.6%)		399/851 (46.9%)
General disorders
Constitutional	365/862 (42.3%)		434/860 (50.5%)		403/854 (47.2%)		367/846 (43.4%)		363/851 (42.7%)
Pain	317/862 (36.8%)		301/860 (35%)		294/854 (34.4%)		295/846 (34.9%)		289/851 (34%)
Hepatobiliary disorders
Hepatic	43/862 (5%)		96/860 (11.2%)		42/854 (4.9%)		39/846 (4.6%)		79/851 (9.3%)
Immune system disorders
Allergy	65/862 (7.5%)		42/860 (4.9%)		54/854 (6.3%)		39/846 (4.6%)		47/851 (5.5%)
Infections and infestations
Infection/Fever	135/862 (15.7%)		196/860 (22.8%)		199/854 (23.3%)		143/846 (16.9%)		147/851 (17.3%)
Metabolism and nutrition disorders
Metabolic	118/862 (13.7%)		98/860 (11.4%)		107/854 (12.5%)		79/846 (9.3%)		97/851 (11.4%)
Musculoskeletal and connective tissue disorders
Musculoskeletal	55/862 (6.4%)		62/860 (7.2%)		52/854 (6.1%)		44/846 (5.2%)		45/851 (5.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
2nd Primary	70/862 (8.1%)		94/860 (10.9%)		85/854 (10%)		74/846 (8.7%)		85/851 (10%)
Nervous system disorders
Neurologic	117/862 (13.6%)		135/860 (15.7%)		110/854 (12.9%)		90/846 (10.6%)		119/851 (14%)
Peripheral neurologic	207/862 (24%)		232/860 (27%)		207/854 (24.2%)		134/846 (15.8%)		144/851 (16.9%)
Renal and urinary disorders
Genitourinary/Renal	46/862 (5.3%)		53/860 (6.2%)		56/854 (6.6%)		36/846 (4.3%)		42/851 (4.9%)
Reproductive system and breast disorders
Sexual	4/862 (0.5%)		9/860 (1%)		11/854 (1.3%)		6/846 (0.7%)		5/851 (0.6%)
Respiratory, thoracic and mediastinal disorders
Pulmonary	104/861 (12.1%)		129/860 (15%)		118/854 (13.8%)		106/846 (12.5%)		145/851 (17%)
Skin and subcutaneous tissue disorders
Dermatologic	63/862 (7.3%)		61/860 (7.1%)		109/854 (12.8%)		47/846 (5.6%)		64/851 (7.5%)
Vascular disorders
Coagulation	10/862 (1.2%)		12/860 (1.4%)		6/854 (0.7%)		14/846 (1.7%)		10/851 (1.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.