Intraperitoneal vs Intravenous Chemotherapy Following Neoadjuvant Chemotherapy in Ovarian Cancer

NCT00993655 | Completed Phase 2 Results DMC FDA Drug

• 6 other identifiers: OV21CAN-NCIC-OV21UCL08/0379GEICO-0902SWOG OV.21CDR0000655241
• Study Type: interventional
• Target: 275
• Locations: 4 countries
• Sites: 50

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.

Conditions

Fallopian Tube Cancer; Metastatic Cancer; Ovarian Cancer; Peritoneal Cavity Cancer

Keywords

peritoneal cavity cancer; fallopian tube cancer; stage II ovarian epithelial cancer; stage III ovarian epithelial cancer; stage IV ovarian epithelial cancer; malignant pleural effusion; ovarian clear cell cystadenocarcinoma; ovarian clear cell tumor with proliferating activity

Outcome Measures

Primary Outcomes (1)

• 9-month Progression Rate Post-randomization

  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.

  9 months

Secondary Outcomes (2)

• Progression Free Survival

  During the study with median follow-up of 33 months

• Overall Survival

  During the study with median follow-up of 33 months

Study Arms (3)

IV carboplatin + IV paclitaxel

ACTIVE COMPARATOR

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

Drug: carboplatin; Drug: paclitaxel

IP cisplatin + IV/IP paclitaxel

ACTIVE COMPARATOR

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)

Drug: cisplatin; Drug: paclitaxel

IP carboplatin + IV/IP paclitaxel

ACTIVE COMPARATOR

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

Drug: carboplatin; Drug: paclitaxel

Interventions

carboplatin DRUG

Carboplatin AUC 5 if measured GFR or AUC6 if calculated GFR intravenous or intraperitoneal.

IP carboplatin + IV/IP paclitaxel; IV carboplatin + IV paclitaxel

cisplatin DRUG

Cisplatin 75 mg/m2 intraperitoneal day 1

IP cisplatin + IV/IP paclitaxel

paclitaxel DRUG

Paclitaxel 135 mg/m2 intravenous day 1 plus Paclitaxel 60 mg/m2 intraperitoneal or intravenously day 8. Cycles given Q 21 days x 3 cycles

IP carboplatin + IV/IP paclitaxel; IP cisplatin + IV/IP paclitaxel; IV carboplatin + IV paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed ovarian epithelial, primary serous type peritoneal, or fallopian tube carcinoma * Patients with ovarian cancer of the clear cell histology are eligible. Histologic confirmation is preferably by biopsy or limited excision prior to neo-adjuvant treatment. If the diagnosis prior to neo-adjuvant chemotherapy is based on cytology, histologic confirmation is required prior to randomization. Histologic confirmation can be obtained at the time of debulking surgery by intra-operative frozen section, thus permitting intra-operative randomization, or by final pathologic review of the resected specimen if randomization is to be performed following debulking surgery. * Initial FIGO stage IIB-III disease * Stage IV disease allowed provided the only criterion for stage IV disease is the presence of a pleural effusion confirmed to be associated with positive cytology for ovarian cancer * Completed ≥ 3 but no more than 4 courses of platinum-based neoadjuvant chemotherapy prior to the first debulking surgery * Meets the following criteria for surgical treatment prior to randomization: * Initial Diagnosis: No debulking surgery was attempted or completed. * The patient's first cytoreductive (debulking) surgery must be after neoadjuvant chemotherapy (Delayed Primary Debulking). The delayed primary debulking surgery must be completed no more than 4 weeks after commencing administering of the last cycle of neoadjuvant chemotherapy and must be completed no more than 6 weeks prior to randomization. * Surgery will include total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy and any additional procedures required to achieve maximal cytoreduction with residual disease of 1 cm or less as assessed by the surgeon at the end of surgery. * Delayed primary debulking surgery must be completed no more than 4 weeks after the last course of neoadjuvant chemotherapy and must be completed no more than 6 weeks prior to randomization * Surgery will include total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and any additional procedures required to achieve maximal cytoreduction with residual disease of ≤ 1 cm as assessed by the surgeon at the end of surgery * No borderline ovarian tumors (i.e., tumors of low malignant potential) alone * No mucinous tumor PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Life expectancy ≥ 12 weeks * Granulocyte count ≥ 1.5 x 10\^9/L * Platelet count ≥ 100 x 10\^9/L * Serum creatinine ≤ upper limit of normal (ULN) OR \> ULN to ≤ 1.25 ULN provided measured creatinine clearance is \> 60 mL/min * Serum bilirubin normal * AST/ALT ≤ 2.5 times ULN * Fertile patients must use effective contraception * Able (i.e., sufficiently fluent) and willing to complete the quality of life questionnaires * Accessible for treatment and follow-up * No history of other malignancy, except adequately treated nonmelanoma skin cancer, curatively treated carcinoma in situ of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years * No uncontrolled atrial or ventricular arrhythmias including second or third degree heart block unless managed with implanted pacemaker * Patients with a history of first degree heart block are eligible * No documented myocardial infarction within the past 6 months preceding randomization (pretreatment ECG evidence only of infarct will not exclude patients) * No diagnosis of bowel obstruction * No serious illness or medical condition which would not permit the patient to be managed according to protocol including, but not limited to, any of the following: * Prior allergic reactions to drugs containing cremophor or to compounds chemically related to cisplatin, paclitaxel, or carboplatin * Symptomatic congestive heart failure within the past 6 months or other conditions which would lead to a contraindication of a high-volume saline diuresis * History of significant neurologic or psychiatric disorder which would impair the ability to obtain consent * Active uncontrolled infection * Persistent peripheral neuropathy or hearing loss ≥ grade 2 resulting from prior therapy * Extensive intraperitoneal adhesion intra- or post-operatively which would impede intraperitoneal treatment delivery PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior therapy for ovarian cancer, except for neoadjuvant platinum-based chemotherapy and surgery * No concurrent intraperitoneal adhesion barriers * No other concurrent anticancer treatment, including cytotoxic agents, biological response modifiers, immunotherapy, anticancer hormone therapy, or investigational drug therapy * No other concurrent experimental drugs or anticancer therapy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• National Cancer Institute (NCI): collaborator
• Grupo Español de Investigación en Cáncer de Ovario: collaborator
• Cancer Research UK: collaborator
• SWOG Cancer Research Network: collaborator

Study Sites (50)

Mercy-Springfield

Springfield, Missouri, 65804, United States

Location

CoxHealth

Springfield, Missouri, 65807, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73190-0001, United States

Location

Women and Infants Hospital of Rhode Island

Providence, Rhode Island, 02905, United States

Location

Univ of Utah (Huntsman Cancer Institute)

Salt Lake City, Utah, 84132, United States

Location

Northwest CCOP - Multicare Health System

Tacoma, Washington, 98415, United States

Location

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BCCA - Cancer Centre for the Southern Interior

Kelowna, British Columbia, V1Y 5L3, Canada

Location

BCCA - Fraser Valley Cancer Centre

Surrey, British Columbia, V3V 1Z2, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Regional Health Authority B, Zone 2

Saint John, New Brunswick, E2L 4L2, Canada

Location

Dr. H. Bliss Murphy Cancer Centre

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

Location

QEII Health Sciences Centre

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Cancer Centre of Southeastern Ontario at Kingston

Kingston, Ontario, K7L 5P9, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

Thunder Bay Regional Health Science Centre

Thunder Bay, Ontario, P7B 6V4, Canada

Location

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Hopital Maisonneuve-Rosemont

Montreal, Quebec, H1T 2M4, Canada

Location

CHUM - Hopital Notre-Dame

Montreal, Quebec, H2L 4M1, Canada

Location

McGill University - Dept. Oncology

Montreal, Quebec, H2W 1S6, Canada

Location

CHUQ-Pavillon Hotel-Dieu de Quebec

Québec, Quebec, G1R 2J6, Canada

Location

Centre hospitalier universitaire de Sherbrooke

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Instituto Catalan de Oncologia - L'Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital Fundacion Alcorcon

Alcorcón, Madrid, 28922, Spain

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Corporacio Sanitaria Clinic

Barcelona, 08036, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital Gregorio Maranon

Madrid, 28009, Spain

Location

Centro Oncologico MD Anderson - Madrid

Madrid, 28033, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Fundacion Instituto Valenciano de Oncologia

Valencia, 46009, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

The Clatterbridge Center for Oncology - Liverpool

Metropolitan Borough of Wirral, Bebington, CH63 4JY, United Kingdom

Location

Mount Vernon Hospital - Middlesex

Middlesex, Northwood, HA6 2RN, United Kingdom

Location

St. George's Hospital - London

London, Tooting, SW17 0QT, United Kingdom

Location

Wexham Park Hospital

Slough, Wexham, SL2 4HL, United Kingdom

Location

The Christie Hospital - Manchester

Manchester, Withington, M20 4BX, United Kingdom

Location

The Western General Hospital - Edinburgh

Edinburgh, EH4 2XU, United Kingdom

Location

St. James University Hospital - Leeds

Leeds, LS9 7TF, United Kingdom

Location

Liverpool Women's Hospital - Liverpool

Liverpool, L8 755, United Kingdom

Location

St. Bartholomew's Hospital - London

London, EC1M 6BQ, United Kingdom

Location

The Royal Marsden Hospital - London

London, SW3 6JJ, United Kingdom

Location

The Hammersmith Hospital - London

London, W12 0HS, United Kingdom

Location

University College London Hospital - London

London, W1T 4TJ, United Kingdom

Location

St Marys Hospital - Manchester

Manchester, M13 0JH, United Kingdom

Location

The Churchill Hospital - Oxford

Oxford, OX3 7LJ, United Kingdom

Location

The Derriford Hospital - Plymouth

Plymouth, PL6 8DH, United Kingdom

Location

Related Publications (1)

• Provencher DM, Gallagher CJ, Parulekar WR, Ledermann JA, Armstrong DK, Brundage M, Gourley C, Romero I, Gonzalez-Martin A, Feeney M, Bessette P, Hall M, Weberpals JI, Hall G, Lau SK, Gauthier P, Fung-Kee-Fung M, Eisenhauer EA, Winch C, Tu D, MacKay HJ. OV21/PETROC: a randomized Gynecologic Cancer Intergroup phase II study of intraperitoneal versus intravenous chemotherapy following neoadjuvant chemotherapy and optimal debulking surgery in epithelial ovarian cancer. Ann Oncol. 2018 Feb 1;29(2):431-438. doi: 10.1093/annonc/mdx754.

  PMID: 29186319 RESULT

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Neoplasm Metastasis; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Pleural Effusion, Malignant

Interventions

Carboplatin; Cisplatin; Paclitaxel

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Pleural Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Pleural Effusion; Pleural Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Results Point of Contact

• Title: Senior Biostatistician
• Organization: Canadian Cancer Trials Group

6135336430

Study Officials

• Helen J. Mackay, MD

  Princess Margaret Hospital, Canada

  STUDY CHAIR

• Diane M. Provencher, MD, FRCS, FACOG

  Hopital Notre-Dame du CHUM

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2009
• First Posted: October 12, 2009
• Study Start: March 3, 2010
• Primary Completion: March 10, 2016
• Study Completion: July 11, 2016
• Last Updated: August 28, 2023
• Results First Posted: August 10, 2017

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (6); ES (10); CA (19); GB (15)