Brief Title
Intraperitoneal vs Intravenous Chemotherapy Following Neoadjuvant Chemotherapy in Ovarian Cancer
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
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
9-month Progression Rate Post-randomization
Secondary Outcome
Progression Free Survival
Condition
Fallopian Tube Cancer
Intervention
carboplatin
Study Arms / Comparison Groups
IV carboplatin + IV paclitaxel
Description: 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
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
275
Start Date
September 11, 2009
Completion Date
July 11, 2016
Primary Completion Date
March 10, 2016
Eligibility Criteria
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
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Helen J. Mackay, MD, ,
Location Countries
Canada
Location Countries
Canada
Administrative Informations
NCT ID
NCT00993655
Organization ID
OV21
Secondary IDs
CAN-NCIC-OV21
Responsible Party
Sponsor
Study Sponsor
Canadian Cancer Trials Group
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Helen J. Mackay, MD, Study Chair, Princess Margaret Hospital, Canada
Verification Date
March 2020