Comparing Combination Chemotherapy Regimens in Treating Patients With Stage IIB, Stage IIC, Stage III, or Stage IV Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer

OBJECTIVES:

Primary

- To determine if intraperitoneal platinum-based chemotherapy leads to 9 month
progression free survival rate as compared with intravenous chemotherapy in patients
with stage IIB-III or stage IV (on the basis of pleural effusion only with positive
cytology) ovarian epithelial, serous type peritoneal, or fallopian tube cancer who have
received optimal debulking surgery following neoadjuvant intravenous chemotherapy.

- To identify which of the two IP regimens will continue into the expanded phase II
portion of the trial.

- To compare the efficacy of the selected IP plus IV chemotherapy regimen versus IV
carboplatin plus paclitaxel in these patients.

Secondary

- To compare IP plus IV chemotherapy versus IV carboplatin plus paclitaxel with respect
to progression free survival, overall survival, toxic effects, quality of life, and
economic evaluation.

- To determine components of nursing interventions associated with administering
intraperitoneal therapy and to correlate these interventions with treatment efficacy,
toxic effects, and quality of life.

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.

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