Intraperitoneal vs Intravenous Chemotherapy Following Neoadjuvant Chemotherapy in Ovarian Cancer

Ovarian Cancer Clinical Trial

Official title:

A Phase II Study of Intraperitoneal (IP) Plus Intravenous (IV) Chemotherapy Versus IV Carboplatin Plus Paclitaxel in Patients With Epithelial Ovarian Cancer Optimally Debulked at Surgery Following Neoadjuvant Intravenous Chemotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00993655
• Other study ID #: OV21
• Secondary ID: CAN-NCIC-OV21UCL
• Status: Completed
• Phase: Phase 2
• Start date: March 3, 2010
• Est. completion date: July 11, 2016

Study information

• Verified date: March 2020
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 275
• Est. completion date: July 11, 2016
• Est. primary completion date: March 10, 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Metastatic Cancer
• Ovarian Cancer
• Ovarian Neoplasms
• Peritoneal Cavity Cancer

Intervention

Drug:
• carboplatin
Carboplatin AUC 5 if measured GFR or AUC6 if calculated GFR intravenous or intraperitoneal.
• cisplatin
Cisplatin 75 mg/m2 intraperitoneal day 1
• paclitaxel
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

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	QEII Health Sciences Centre	Halifax	Nova Scotia
Canada	BCCA - Cancer Centre for the Southern Interior	Kelowna	British Columbia
Canada	Cancer Centre of Southeastern Ontario at Kingston	Kingston	Ontario
Canada	London Regional Cancer Program	London	Ontario
Canada	CHUM - Hopital Notre-Dame	Montreal	Quebec
Canada	Hopital Maisonneuve-Rosemont	Montreal	Quebec
Canada	McGill University - Dept. Oncology	Montreal	Quebec
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	CHUQ-Pavillon Hotel-Dieu de Quebec	Quebec City	Quebec
Canada	Regional Health Authority B, Zone 2	Saint John	New Brunswick
Canada	Centre hospitalier universitaire de Sherbrooke	Sherbrooke	Quebec
Canada	Dr. H. Bliss Murphy Cancer Centre	St. John's	Newfoundland and Labrador
Canada	BCCA - Fraser Valley Cancer Centre	Surrey	British Columbia
Canada	Thunder Bay Regional Health Science Centre	Thunder Bay	Ontario
Canada	Univ. Health Network-Princess Margaret Hospital	Toronto	Ontario
Canada	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Spain	Hospital Fundacion Alcorcon	Alcorcon	Madrid
Spain	Corporacio Sanitaria Clinic	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Instituto Catalan de Oncologia - L'Hospitalet	Hospitalet de Llobregat	Barcelona
Spain	Centro Oncologico MD Anderson - Madrid	Madrid
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Gregorio Maranon	Madrid
Spain	Fundacion Instituto Valenciano de Oncologia	Valencia
Spain	Hospital Clinico Universitario de Valencia	Valencia
United Kingdom	The Western General Hospital - Edinburgh	Edinburgh
United Kingdom	St. James University Hospital - Leeds	Leeds
United Kingdom	Liverpool Women's Hospital - Liverpool	Liverpool
United Kingdom	St. Bartholomew's Hospital - London	London
United Kingdom	St. George's Hospital - London	London	Tooting
United Kingdom	The Hammersmith Hospital - London	London
United Kingdom	The Royal Marsden Hospital - London	London
United Kingdom	University College London Hospital - London	London
United Kingdom	St Marys Hospital - Manchester	Manchester
United Kingdom	The Christie Hospital - Manchester	Manchester	Withington
United Kingdom	Mount Vernon Hospital - Middlesex	Middlesex	Northwood
United Kingdom	The Churchill Hospital - Oxford	Oxford
United Kingdom	The Derriford Hospital - Plymouth	Plymouth
United Kingdom	Wexham Park Hospital	Slough	Wexham
United Kingdom	The Clatterbridge Center for Oncology - Liverpool	Wirral	Bebington
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Women and Infants Hospital of Rhode Island	Providence	Rhode Island
United States	Univ of Utah (Huntsman Cancer Institute)	Salt Lake City	Utah
United States	CoxHealth	Springfield	Missouri
United States	Mercy-Springfield	Springfield	Missouri
United States	Northwest CCOP - Multicare Health System	Tacoma	Washington

Sponsors (5)

Lead Sponsor	Collaborator
Canadian Cancer Trials Group	Cancer Research UK, Grupo Español de Investigación en Cáncer de Ovario, National Cancer Institute (NCI), SWOG Cancer Research Network

Countries where clinical trial is conducted

United States,  Canada,  Spain,  United Kingdom, 

References & 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. OV — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Progression Free Survival	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.	During the study with median follow-up of 33 months
Secondary	Overall Survival	Time from the day of randomization to death from any cause.	During the study with median follow-up of 33 months