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Intraperitoneal vs Intravenous Chemotherapy Following Neoadjuvant Chemotherapy in Ovarian Cancer

Phase 2
Completed
Conditions
Fallopian Tube Cancer
Metastatic Cancer
Ovarian Cancer
Peritoneal Cavity Cancer
Interventions
Registration Number
NCT00993655
Lead Sponsor
Canadian Cancer Trials Group
Brief Summary

RATIONALE: Drugs used in chemotherapy, such as paclitaxel, carboplatin, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) and giving them in different ways may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective in treating patients with ovarian epithelial cancer, primary peritoneal cancer, and fallopian tube cancer.

PURPOSE: This randomized phase II trial is comparing the side effects of three combination chemotherapy regimens and to see how well they work in treating patients with stage IIB, stage IIC, stage III, or stage IV ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer.

Detailed Description

OBJECTIVES:

Primary

* To compare the efficacy of the selected IP chemotherapy regimen (Arm 3: IV paclitaxel and IP carboplatin plus day 8 IP paclitaxel) versus IV carboplatin plus paclitaxel (Arm 1) in patients with epithelial ovarian cancer optimally debulked at surgery following neoadjuvant intravenous chemotherapy. Nine month progressive rate post randomization is the primary endpoint for assessment of efficacy.

Secondary

* To compare IP plus IV chemotherapy versus IV carboplatin plus paclitaxel with respect to progression free survival and overall survival.

OUTLINE: This is a multicenter study. Patients are stratified according to cooperative group, residual disease (observable \[e.g., macroscopic\] disease that is evident at end of delayed primary debulking surgery vs no evidence of observable disease at end of delayed primary debulking surgery), reason for delayed primary debulking surgery at initial diagnosis (nonresectable disease vs other reasons), and timing of intraperitoneal catheter insertion (intra-operative catheter insertion vs post-operative insertion).

* Phase II: Patients are randomized to 1 of 3 treatment groups.

* ARM 1: Paclitaxel 135 mg/m2 intravenous day 1 plus Carboplatin AUC 5 if measured GFR or AUC6 if estimated GFR intravenous day 1; Paclitaxel 60 mg/m2 intravenous day 8. Cycles given Q 21 days x 3 cycles

* ARM 2: Paclitaxel 135 mg/m2 intravenous day 1 plus Cisplatin 75 mg/m2 intraperitoneal day 1; Paclitaxel 60 mg/m2 intraperitoneal day 8. Cycles given Q 21 days x 3 cycles (Phase II cisplatin arm closed to accrual on 2014-Feb-03)

* ARM 3: Paclitaxel 135 mg/m2 intravenous day 1 plus Carboplatin AUC 5 if measured GFR or AUC6 if estimated GFR intraperitoneal day 1; Paclitaxel 60 mg/m2 intraperitoneal day 8. Cycles given Q 21 days x 3 cycles.

Patients also receive carboplatin IP on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.

* Expanded Phase II: Patients are randomized to 1 of 2 treatment groups.

* Arm I: Patients receive paclitaxel and carboplatin as in phase II, arm I.

* Arm III: Patients receive paclitaxel and cisplatin as in phase II, arm II or paclitaxel and carboplatin as in phase II, arm III.

Patients complete quality of life questionnaires EORTC QLQ-C30, ovarian cancer module (EORTC QLQ-OV28), and FACT/GOG-Ntx at baseline, on day 1 of courses 2 and 3, at 3, 6 and 12 months after completion of study treatment, and then annually until disease progression, death, or initiation of second-line therapy.

After completion of study treatment, patients are followed at 6 weeks, every 3 months for 2 years, every 6 months for 2 years, and then annually until progression, death, or initiation of second-line therapy.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
275
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
IP cisplatin + IV/IP paclitaxelcisplatinARM 2: Paclitaxel 135 mg/m2 intravenous day 1 plus Cisplatin 75 mg/m2 intraperitoneal day 1; Paclitaxel 60 mg/m2 intraperitoneal day 8. Cycles given Q 21 days x 3 cycles (Phase II cisplatin arm closed to accrual on 2014-FEB-03)
IP cisplatin + IV/IP paclitaxelpaclitaxelARM 2: Paclitaxel 135 mg/m2 intravenous day 1 plus Cisplatin 75 mg/m2 intraperitoneal day 1; Paclitaxel 60 mg/m2 intraperitoneal day 8. Cycles given Q 21 days x 3 cycles (Phase II cisplatin arm closed to accrual on 2014-FEB-03)
IP carboplatin + IV/IP paclitaxelcarboplatinARM 3: Paclitaxel 135 mg/m2 intravenous day 1 plus Carboplatin AUC 5 if measured GFR or AUC6 if estimated GFR intraperitoneal day 1; Paclitaxel 60 mg/m2 intraperitoneal day 8. Cycles given Q 21 days x 3 cycles
IV carboplatin + IV paclitaxelcarboplatinARM 1: Paclitaxel 135 mg/m2 intravenous day 1 plus Carboplatin AUC 5 if measured GFR or AUC6 if estimated GFR intravenous day 1; Paclitaxel 60 mg/m2 intravenous day 8. Cycles given Q 21 days x 3 cycles
IV carboplatin + IV paclitaxelpaclitaxelARM 1: Paclitaxel 135 mg/m2 intravenous day 1 plus Carboplatin AUC 5 if measured GFR or AUC6 if estimated GFR intravenous day 1; Paclitaxel 60 mg/m2 intravenous day 8. Cycles given Q 21 days x 3 cycles
IP carboplatin + IV/IP paclitaxelpaclitaxelARM 3: Paclitaxel 135 mg/m2 intravenous day 1 plus Carboplatin AUC 5 if measured GFR or AUC6 if estimated GFR intraperitoneal day 1; Paclitaxel 60 mg/m2 intraperitoneal day 8. Cycles given Q 21 days x 3 cycles
Primary Outcome Measures
NameTimeMethod
9-month Progression Rate Post-randomization9 months

It is defined as proportion of patients who had progressed at or before 9 months after randomization, i.e., the time from the randomization to the date when the first observation of disease progression (earliest of the date when the first CA 125 meets progression definition and the date of first objective relapse or progression, defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions, recorded) has been documented or when death due to any cause has been observed was less than or equal to 9 months.

Secondary Outcome Measures
NameTimeMethod
Overall SurvivalDuring the study with median follow-up of 33 months

Time from the day of randomization to death from any cause.

Progression Free SurvivalDuring the study with median follow-up of 33 months

Time from the day of randomization until the time when first observation of disease progression (earliest of the dates of first CA125 which meets progression definition and first objective relapse or progression defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions, has been documented or when death due to any cause has been observed.

Trial Locations

Locations (50)

Women and Infants Hospital of Rhode Island

🇺🇸

Providence, Rhode Island, United States

London Regional Cancer Program

🇨🇦

London, Ontario, Canada

CoxHealth

🇺🇸

Springfield, Missouri, United States

Tom Baker Cancer Centre

🇨🇦

Calgary, Alberta, Canada

The Western General Hospital - Edinburgh

🇬🇧

Edinburgh, United Kingdom

Mercy-Springfield

🇺🇸

Springfield, Missouri, United States

QEII Health Sciences Centre

🇨🇦

Halifax, Nova Scotia, Canada

CancerCare Manitoba

🇨🇦

Winnipeg, Manitoba, Canada

Hospital Fundacion Alcorcon

🇪🇸

Alcorcon, Madrid, Spain

The Hammersmith Hospital - London

🇬🇧

London, United Kingdom

Thunder Bay Regional Health Science Centre

🇨🇦

Thunder Bay, Ontario, Canada

Mount Vernon Hospital - Middlesex

🇬🇧

Middlesex, Northwood, United Kingdom

Hospital Clinico San Carlos

🇪🇸

Madrid, Spain

St. George's Hospital - London

🇬🇧

London, Tooting, United Kingdom

Regional Health Authority B, Zone 2

🇨🇦

Saint John, New Brunswick, Canada

Cancer Centre of Southeastern Ontario at Kingston

🇨🇦

Kingston, Ontario, Canada

Univ. Health Network-Princess Margaret Hospital

🇨🇦

Toronto, Ontario, Canada

Centre hospitalier universitaire de Sherbrooke

🇨🇦

Sherbrooke, Quebec, Canada

University of Oklahoma Health Sciences Center

🇺🇸

Oklahoma City, Oklahoma, United States

BCCA - Fraser Valley Cancer Centre

🇨🇦

Surrey, British Columbia, Canada

BCCA - Vancouver Cancer Centre

🇨🇦

Vancouver, British Columbia, Canada

Dr. H. Bliss Murphy Cancer Centre

🇨🇦

St. John's, Newfoundland and Labrador, Canada

St. Bartholomew's Hospital - London

🇬🇧

London, United Kingdom

The Christie Hospital - Manchester

🇬🇧

Manchester, Withington, United Kingdom

Hopital Maisonneuve-Rosemont

🇨🇦

Montreal, Quebec, Canada

CHUM - Hopital Notre-Dame

🇨🇦

Montreal, Quebec, Canada

BCCA - Cancer Centre for the Southern Interior

🇨🇦

Kelowna, British Columbia, Canada

Univ of Utah (Huntsman Cancer Institute)

🇺🇸

Salt Lake City, Utah, United States

Cross Cancer Institute

🇨🇦

Edmonton, Alberta, Canada

Ottawa Hospital Research Institute

🇨🇦

Ottawa, Ontario, Canada

McGill University - Dept. Oncology

🇨🇦

Montreal, Quebec, Canada

CHUQ-Pavillon Hotel-Dieu de Quebec

🇨🇦

Quebec City, Quebec, Canada

Instituto Catalan de Oncologia - L'Hospitalet

🇪🇸

Hospitalet de Llobregat, Barcelona, Spain

Hospital Vall d'Hebron

🇪🇸

Barcelona, Spain

Corporacio Sanitaria Clinic

🇪🇸

Barcelona, Spain

Hospital de la Santa Creu i Sant Pau

🇪🇸

Barcelona, Spain

Hospital Gregorio Maranon

🇪🇸

Madrid, Spain

Hospital Clinico Universitario de Valencia

🇪🇸

Valencia, Spain

The Clatterbridge Center for Oncology - Liverpool

🇬🇧

Wirral, Bebington, United Kingdom

Fundacion Instituto Valenciano de Oncologia

🇪🇸

Valencia, Spain

St. James University Hospital - Leeds

🇬🇧

Leeds, United Kingdom

Liverpool Women's Hospital - Liverpool

🇬🇧

Liverpool, United Kingdom

The Royal Marsden Hospital - London

🇬🇧

London, United Kingdom

St Marys Hospital - Manchester

🇬🇧

Manchester, United Kingdom

The Churchill Hospital - Oxford

🇬🇧

Oxford, United Kingdom

The Derriford Hospital - Plymouth

🇬🇧

Plymouth, United Kingdom

Wexham Park Hospital

🇬🇧

Slough, Wexham, United Kingdom

Centro Oncologico MD Anderson - Madrid

🇪🇸

Madrid, Spain

Northwest CCOP - Multicare Health System

🇺🇸

Tacoma, Washington, United States

University College London Hospital - London

🇬🇧

London, United Kingdom

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