Two Different Schedules of Carboplatin, Paclitaxel, Gemcitabine, and Surgery in Treating Patients With Newly Diagnosed Stage IIIC or Stage IV Primary Epithelial Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

September 16, 2013 updated by: Warwick Medical School

A Randomised Feasibility Study of Extended Chemotherapy With Neoadjuvant Carboplatin, Then Surgery Followed by Adjuvant Paclitaxel and Gemcitabine Verses Neoadjuvant Gemcitabine and Carboplatin, Then Surgery, Followed by Adjuvant Paclitaxel

RATIONALE: Drugs used in chemotherapy, such as carboplatin, gemcitabine, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery. It is not yet known which treatment regimen may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying how well giving one of two chemotherapy regimens containing carboplatin, gemcitabine, and paclitaxel works in treating patients undergoing surgery for newly diagnosed primary stage IIIC or stage IV ovarian cancer, fallopian tube cancer, or primary peritoneal cancer.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

To examine and compare the feasibility of two sequential neoadjuvant regimens in patients with newly diagnosed, stage IIIC-IV ovarian or peritoneal carcinoma.
To confirm the feasibility of extended sequential regimens offering 6+6 courses of chemotherapy in patients presenting with inoperable disease.
To establish the feasibility of biweekly paclitaxel with vs without gemcitabine hydrochloride in the adjuvant phase, after carboplatin neoadjuvant induction.

OUTLINE: This is a multicenter study. Patients are stratified according to serum albumin (< 30 g/dL vs 30-35 g/dL vs > 35 g/dL), FIGO stage (stage IIIC vs stage IV), and histological grade (well-differentiated [grade 1] vs moderately well-differentiated [grade 2] vs poorly differentiated [grade 3]). Patients are randomized to 1 of 2 treatment arms.

Neoadjuvant therapy:
- Arm I: Patients receive carboplatin IV over 1 hour and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive carboplatin IV over 1 hour on day 1. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

In both arms, patients with disease progression are switched to adjuvant paclitaxel-based chemotherapy. Patients with responding disease after switching regimens may undergo debulking surgery at the investigator's discretion.

Surgery: After completion of 6 courses of chemotherapy, all patients are evaluated for surgery. Patients with questionable operability based on clinical or radiological criteria are re-assessed laparoscopically. Patients judged to have disease that is amenable to optimal debulking at laparotomy are recommended for debulking surgery. Patients judged to have disease that is not amenable to optimal debulking are reconsidered for surgery after they receive an additional 6 courses of chemotherapy. Patients with disease progression after completion of 12 courses of chemotherapy undergo laparotomy only if there is a clinically pressing need to palliate their condition and if surgery offers some prospect of achieving this result (e.g., palliation for bowel obstruction).
Adjuvant therapy:
- Arm I: Patients receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive paclitaxel IV over 3 hours and gemcitabine hydrochloride IV over 30 minutes on day 1. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients complete quality of life questionnaires at baseline, after completion of course 6 of neoadjuvant therapy, before course 7, and at the end of study treatment.

After completion of study therapy, patients are followed periodically for up to 10 years.

Study Type

Interventional

Enrollment (Anticipated)

Phase

Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United Kingdom
- England
  - Birmingham, England, United Kingdom, B9 5SS
    - Birmingham Heartlands Hospital
  - Birmingham, England, United Kingdom, B15 2TH
    - Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
  - Birmingham, England, United Kingdom, B75 7RR
    - Good Hope Hospital
  - Wolverhampton, England, United Kingdom, WV10 0QP
    - New Cross Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

Female

Description

DISEASE CHARACTERISTICS:

Clinically, radiologically, and histologically confirmed diagnosis of 1 of the following:
- Primary epithelial ovarian cancer
- Primary peritoneal carcinoma
- Ovarian carcinosarcoma
- Fallopian tube carcinoma
Newly diagnosed, stage IIIC/IV disease with or without ascites
None of the following histologies allowed:
- Mucinous
- Classic clear cell
- Micropapillary or microacinar borderline tumors with or without invasive implants
Unsuitable for primary debulking surgery, as defined by the following:
- Laparoscopic or other minor surgical-staging procedures
- Supplementary clinical and radiological assessments
Presenting with factors affecting suitability for successful complete resection and necessarily prompting laparoscopic assessment, including any of the following:
- CT scan or MRI evidence of peritoneal carcinomatosis, extensive mesenteric infiltration, diaphragmatic involvement, extensive retroperitoneal involvement, and cytologically verified malignant pleural effusion and/or ascites
- Clinical evidence of ascites with radiological evidence of multisite disease
- Clinical evidence of pelvic infiltration and radiological evidence of multisite disease
- FIGO stage IV disease, including cervical/supraclavicular lymphadenopathy, intrahepatic parenchymal metastases, or cytologically confirmed malignant pleural effusion
No known brain metastases

PATIENT CHARACTERISTICS:

ECOG performance status 0-3
Life expectancy ≥ 3 months
WBC > 3.0/mm³
Platelet count ≥ 100,000/mm³
ANC ≥ 1,500/mm³
AST and ALT < 2.5 times upper limit of normal (ULN)
Alkaline phosphatase < 2.5 times ULN
Bilirubin < 1.5 times ULN
Estimated glomerular filtration rate ≥ 30 mL/min
No diabetics, hypertensive smokers, or other patients with pre-existing occult neuropathic deficits
No poorly controlled, potentially serious medical conditions, including any of the following:
- Cerebrovascular events within the past 12 months
- Severe chronic respiratory conditions requiring prior hospitalization
- Active infections
- Poorly controlled seizures
- Morbid psychiatric conditions likely to render treatment compliance with the protocol difficult
No other malignancy treated with chemotherapy or radiotherapy except nonmelanoma skin cancer or carcinoma in situ of the cervix
- Prior malignancies disease-free for > 5 years not treated with chemotherapy allowed
No other reasons likely to cause inability to comply with treatment schedule and follow-up
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

See Disease Characteristics

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Masking: None (Open Label)

Number of Arms

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I Patients receive carboplatin IV over 1 hour and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may undergo treatment with paclitaxel and may also receive 6 more courses of neoadjuvant chemotherapy. Patients may then undergo surgery. After surgery, patients receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.	Drug: carboplatin Given IV in one of two schedules Drug: gemcitabine hydrochloride Given IV in one of two schedules Drug: paclitaxel Given IV in one of two schedules
Experimental: Arm II Patients receive carboplatin IV over 1 hour on day 1. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may undergo treatment with paclitaxel and may also receive 6 more courses of neoadjuvant chemotherapy. Patients may then undergo surgery. After surgery, patients receive paclitaxel IV over 3 hours and gemcitabine hydrochloride IV over 30 minutes on day 1. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.	Drug: carboplatin Given IV in one of two schedules Drug: gemcitabine hydrochloride Given IV in one of two schedules Drug: paclitaxel Given IV in one of two schedules

Participant Group / Arm

Intervention / Treatment

Experimental: Arm I

Patients receive carboplatin IV over 1 hour and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may undergo treatment with paclitaxel and may also receive 6 more courses of neoadjuvant chemotherapy. Patients may then undergo surgery. After surgery, patients receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: carboplatin