Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Carboplatin and Paclitaxel With or Without Bevacizumab in Treating Patients With Stage III or Stage IV Ovarian Epithelial, Primary Peritoneal Cancer, or Fallopian Tube Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Active 18 and over NCI GOG-0218 GOG-0218, NCT00262847

Special Category: NCI Web site featured trial, CTSU trial

Objectives

Primary

1. Compare the overall survival of patients with stage III or stage IV ovarian epithelial, primary peritoneal cancer, or fallopian tube cancer treated with carboplatin and paclitaxel vs carboplatin, paclitaxel, and concurrent bevacizumab with vs without extended bevacizumab.

Secondary

1. Compare the duration of progression-free survival of patients treated with these regimens.
2. Compare the incidence of severe toxicity of these regimens in these patients.
3. Compare the quality of life of patients treated with these regimens.

Tertiary

1. Determine the relationship between angiogenic markers and clinical outcome (tumor response, progression-free survival, and overall survival) in patients treated with these regimens.
2. Determine the predictive value of a set of genes whose expression correlates with survival of these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed ovarian epithelial, primary peritoneal*, or fallopian tube cancer
  • Stage III with any gross (macroscopic or palpable) residual disease OR stage IV disease

   [Note: May have co-existing fallopian tube carcinoma in-situ so long as the primary origin of invasive tumor is ovarian or peritoneal.]




• The following histologic epithelial cell types are allowed provided the histologic features of the tumor are compatible with a primary müllerian epithelial adenocarcinoma:
  • Serous adenocarcinoma
  • Endometrioid adenocarcinoma
  • Mucinous adenocarcinoma
  • Undifferentiated carcinoma
  • Clear cell adenocarcinoma
  • Mixed epithelial carcinoma
  • Transitional cell carcinoma
  • Malignant Brenner tumor
  • Adenocarcinoma not otherwise specified



• No borderline ovarian epithelial tumor (formerly "tumors of low malignant potential")
  • Prior diagnosis of a borderline tumor that was surgically resected and an unrelated, new, invasive ovarian epithelial or primary peritoneal cancer that subsequently develops is allowed provided there was no prior chemotherapy for any ovarian tumor



• No recurrent invasive ovarian epithelial cancer treated with surgery only (e.g., stage IA or IB low-grade epithelial ovarian or fallopian tube cancer)



• No synchronous primary endometrial cancer or prior primary endometrial cancer unless all of the following criteria are met:
  • Stage ≤ IB
  • Superficial myometrial invasion without vascular or lymphatic invasion
  • No poorly differentiated subtypes (i.e., papillary serous, clear cell, or other FIGO grade 3 lesions)



• Must have undergone surgery for ovarian epithelial, primary peritoneal, or fallopian tube cancer in the past 1-12 weeks AND have tissue available for histologic evaluation
  • Patients with stage III disease in which the largest maximal diameter of any residual tumor implant a the completion of initial surgery is ≤ 1 cm will be defined as "optimal" (all others will be defined as "suboptimal")



• Measurable or nonmeasurable disease



• No tumor involving active major vessels



• No prior or concurrent CNS disease, including primary brain tumor or brain metastases

Prior/Concurrent Therapy:

Biologic therapy

• No prior targeted therapy for ovarian epithelial or peritoneal primary cancer, including, but not limited to, any of the following:
  • Vaccines
  • Antibodies
  • Tyrosine kinase inhibitors
• No prior bevacizumab
• No other prior antivascular endothelial growth factors (VEGF)
• No other concurrent biologic therapy

Chemotherapy

• See Disease Characteristics
• No prior chemotherapy for abdominal or pelvic tumor including neoadjuvant chemotherapy for their ovarian or primary peritoneal cancer
• More than 3 years since prior adjuvant chemotherapy for localized breast cancer AND patient remains free of recurrent or metastatic disease
• No other concurrent chemotherapy

Endocrine therapy

• Ovarian estrogen with or without progestin replacement therapy as indicated at the lowest effective dose(s) for control of menopausal symptoms at any time allowed
  • No progestins for management of anorexia while on study-directed therapy or prior to disease progression
• No prior hormonal therapy for ovarian, peritoneal primary, or fallopian tube cancer
• No concurrent hormonal therapy

Radiotherapy

• More than 3 years since prior radiotherapy for localized cancer of the breast, head and neck, or skin AND patient remains free of recurrent or metastatic disease
• No prior radiotherapy to the abdominal cavity or pelvis
• No concurrent radiotherapy

Surgery

• See Disease Characteristics
• At least 4 weeks since prior major surgical procedure or open biopsy
• At least 1 week since prior core biopsy
• No concurrent major surgery including abdominal surgery (laparotomy or laparoscopy) prior to disease progression (e.g., colostomy or enterostomy reversal, interval or secondary cytoreductive surgery, or second look surgery

Other

• No prior cancer therapy that would preclude study treatment
• No concurrent consolidation or maintenance therapy
• No other concurrent cytotoxic or anticancer therapy
• No concurrent amifostine or other protective reagents

Patient Characteristics:

Performance status

• GOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm³ without induction or support by granulocyte colony stimulating factors
• Platelet count ≥ 100,000/mm³
• No active bleeding
• No known bleeding disorder or coagulopathy

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• SGOT ≤ 2.5 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN
• INR ≤ 1.5 (2-3 with stable-dose therapeutic warfarin for management of venous thrombosis including pulmonary thromboembolus)
• PTT < 1.2 times ULN
• No acute hepatitis

Renal

• Creatinine ≤ 1.5 times ULN
• Urine protein:creatinine ratio < 1.0

  OR

• Urine protein < 1 g/24-hr urine collection

Cardiovascular

• No New York Heart Association class II-IV congestive heart failure
• No myocardial infarction or unstable angina within the past 6 months
• No uncontrolled hypertension (i.e., blood pressure > 150/90 mm Hg)
• No serious cardiac arrhythmia requiring medication except for patients with asymptomatic atrial fibrillation with a controlled ventricular rate
• No other clinically significant cardiovascular disease
• No clinically significant peripheral vascular disease ≥ grade 2
• No history of cerebral vascular accident, transient ischemic attack, or subarachnoid hemorrhage within the past 6 months

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after completion of study treatment
• No neuropathy (sensory and motor) > grade 1
• No known hypersensitivity to Chinese hamster ovary cell products or recombinant human or humanized antibodies
• No other malignancy within the past 5 years except nonmelanoma skin cancer
• No active infection that requires parenteral antibiotics
• No serious nonhealing wound, ulcer, or bone fracture
• No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
  • Granulating incisions healing by secondary intention with no evidence of fascial dehiscence or infection are allowed
• No other pathological condition that would confer a high risk of bleeding
• No uncontrolled seizures
• No significant traumatic injury within the past 4 weeks
• No clinical symptoms or signs of gastrointestinal obstruction that require parenteral hydration and/or nutrition
• No other medical history or condition that, in the opinion of the investigator, would preclude study participation

Expected Enrollment

A total of 2,000 patients will be accrued for this study.

Outcomes

Progression-free survival measured by RECIST Criteria and Modified Rustin Criteria for CA-125 at baseline, prior to every other course of therapy, every 3 months for 2 years, every 6 months for 3 years, and then annually during follow-up

Overall survival
Severe toxicity and serious adverse events by NCI Common Toxicity Criteria version 3 at baseline, every course of therapy, every 3 months for 2 years, every 6 months for 3 years, and then annually during follow-up
Quality of life by Functional Assessment of Cancer Therapy-Ovarian (Fact-O) at baseline, prior to courses 4, 7, 13, and 21, and then at 6 months after study completion
Translational objectives by angiogenic markers and gene arrays at baseline
Response rate

Outline

This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to stage of disease (III vs IV) or initial performance status (0 vs 1 vs 2). Patients are randomized to 1 of 3 treatment arms.

• Arm I: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Beginning in course 2, patients also receive placebo IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses. Beginning in course 7, patients receive placebo alone IV over 30-90 minutes on day 1. Treatment with placebo repeats every 21 days for up to 22 courses in the absence of disease progression or unacceptable toxicity.



• Arm II: Patients receive paclitaxel and carboplatin as in arm I. Beginning in course 2, patients also receive bevacizumab IV over 30-90 minutes on day 1.Treatment repeats every 21 days for 6 courses. Beginning in course 7, patients receive placebo alone IV over 30-90 minutes on day 1. Treatment with placebo repeats every 21 days for up to 22 courses in the absence of disease progression or unacceptable toxicity.



• Arm III: Patients receive paclitaxel and carboplatin as in arm I. Beginning in course 2, patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses. Beginning in course 7, patients receive bevacizumab alone IV over 30-90 minutes on day 1. Treatment with bevacizumab repeats every 21 days for up to 22 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, before courses 4, 7, 13, and 21, and then at 6 months after study completion.

After completion of study treatment, patients are followed periodically for at least 5 years.

Trial Contact Information

Trial Lead Organizations

Gynecologic Oncology Group

Robert Burger, MD, Protocol chair		Ph: 714-456-7971 Email: raburger@uci.edu
Gini Fleming, MD, Protocol co-chair		Ph: 773-702-6712; 888-824-0200 Email: gfleming@medicine.bsd.uchicago.edu

U.S.A.
Alabama
	Anniston
	Regional Medical Center
		Ellen Spremulli	Ph:  256-235-5877
	Birmingham
	Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
		Clinical Trials Office - Lurleen Wallace Comprehensive Cancer	Ph:  205-934-0309
	Huntsville
	Clearview Cancer Institute
		Clinical Trials Office - Clearview Cancer Institute	Ph:  256-705-4224
	Mobile
	Providence Cancer Center at Providence Hospital
		Paul Schwarzenberger, MD	Ph:  251-435-5892
Alaska
	Anchorage
	Providence Cancer Center
		Clinical Trials Office - Providence Cancer Center	Ph:  907-261-3109
Arizona
	Scottsdale
	Mayo Clinic Scottsdale
		Clinical Trials Office - All Mayo Clinic Locations	Ph:  507-538-7623
Arkansas
	Ft. Smith
	Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
		John Wells, MD	Ph:  479-484-4700 800-333-1305
California
	Arroyo Grande
	Arroyo Grande Community Hospital
		David Palchak, MD	Ph:  805-473-8983
	Burbank
	Providence Saint Joseph Medical Center - Burbank
		Clinical Trials Office - Providence Saint Joseph Medical Center - Burbank	Ph:  818-847-3220
	Concord
	Cancer Care Center at John Muir Health - Concord Campus
		Clinical Trials Office - Cancer Care Center at John Muir Health - Concord Campus	Ph:  925-674-2580
	Fairfield
	North Bay Cancer Center
		Clinical Trials Office - North Bay Cancer Center	Ph:  707-429-6976
	Fremont
	Kaiser Permanente - Fremont
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Fresno
	Cancer Care Associates
		Steven Hager, DO	Ph:  559-326-1222 877-490-4222
	Fullerton
	Virginia K. Crosson Cancer Center at St. Jude Medical Center
		Clinical Trials Office - Virginia K. Crosson Cancer Center	Ph:  714-446-5642
	Hayward
	Kaiser Permanente Medical Center - Hayward
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	La Jolla
	Rebecca and John Moores UCSD Cancer Center
		Clinical Trials Office - Rebecca and John Moores UCSD Cancer Center	Ph:  858-822-5354
			Email: cancercto@ucsd.edu
	Long Beach
	Todd Cancer Institute at Long Beach Memorial Medical Center
		Wendy Brewster, MD, PhD	Ph:  562-933-0900
	Los Angeles
	Jonsson Comprehensive Cancer Center at UCLA
		Clinical Trials Office - Jonsson Comprehensive Cancer Center at UCLA	Ph:  888-798-0719
	Kaiser Permanente Medical Center - Los Angeles
		Scott Lentz, MD	Ph:  323-667-4011 800-954-8000
	Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
		Ilana Cass	Ph:  310-423-3277
	USC/Norris Comprehensive Cancer Center and Hospital
		Clinical Trials Office - USC/Norris Comprehensive Cancer Center and Hospital	Ph:  323-865-0451
	Modesto
	Memorial Medical Center
		Clinical Trials Office - Memorial Medical Center	Ph:  209-572-7116
	Oakland
	Kaiser Permanente Medical Center - Oakland
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Redding
	Mercy Regional Cancer Center at Mercy Medical Center
		Clinical Trials Office - Mercy Regional Cancer Center	Ph:  530-225-7471
	Redwood City
	Kaiser Permanente Medical Center - Redwood City
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Richmond
	Kaiser Permanente Medical Center - Richmond
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Roseville
	Kaiser Permanente Medical Center - Roseville
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Sutter Cancer Center at Roseville Medical Center
		Clinical Trials Office - Sutter Cancer Center	Ph:  916-454-6595
	Sacramento
	Kaiser Permanente Medical Center - Sacramento
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	South Sacramento Kaiser-Permanente Medical Center
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Sutter Cancer Center
		Clinical Trial Office - Sutter Cancer Center	Ph:  916-454-6595
	University of California Davis Cancer Center
		Clinical Trials Office - University of California Davis Cancer Center	Ph:  916-734-3089
	San Francisco
	Kaiser Permanente Medical Center - San Francisco Geary Campus
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	San Francisco General Hospital Medical Center
		John Chan	Ph:  415-206-8000
	UCSF Helen Diller Family Comprehensive Cancer Center
		Clinical Trials Office - UCSF Helen Diller Family Comprehensive Cancer Center	Ph:  877-827-3222
	San Jose
	Kaiser Permanente Medical Center - Santa Teresa
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	San Rafael
	Kaiser Foundation Hospital - San Rafael
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Sana Rosa
	CCOP - Santa Rosa Memorial Hospital
		Ian Anderson, MD	Ph:  707-521-3830
	Santa Clara
	Kaiser Permanente Medical Center - Santa Clara Kiely Campus
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Santa Rosa
	Kaiser Permanente Medical Center - Santa Rosa
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	South San Francisco
	Kaiser Permanente Medical Center - South San Francisco
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Stanford
	Stanford Cancer Center
		Clinical Trials Office - Stanford Cancer Center	Ph:  650-498-7061
			Email: cctoffice@stanford.edu
	Stockton
	Kaiser Permanente Medical Facility - Stockton
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Vallejo
	Kaiser Permanente Medical Center - Vallejo
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Walnut Creek
	John Muir/Mt. Diablo Comprehensive Cancer Center
		Clinical Trials Office - John Muir/Mt. Diablo Comprehensive Cancer Center	Ph:  925-941-4246
	Kaiser Permanente Medical Center - Walnut Creek
		Louis Fehrenbacher, MD	Ph:  707-651-2577
Colorado
	Aurora
	Aurora Presbyterian Hospital
		Eduardo Pajon, MD	Ph:  303-777-2663
	Colorado Gynecologic Oncology Group, PC
		Susan Davidson, MD	Ph:  303-315-7897
	Boulder
	Boulder Community Hospital
		Clinical Trials Office - Boulder Community Hospital	Ph:  303-938-5253
	Colorado Springs
	Memorial Hospital Cancer Center - Colorado Springs
		Clinical Trials Office - Memorial Hospital	Ph:  719-365-2406
	Penrose Cancer Center at Penrose Hospital
		Clinical Trials Office - Penrose Cancer Center	Ph:  719-776-5275
	Denver
	CCOP - Colorado Cancer Research Program
		Eduardo Pajon, MD	Ph:  303-777-2663
	Porter Adventist Hospital
		Eduardo Pajon, MD	Ph:  303-777-2663
	Presbyterian - St. Luke's Medical Center
		Clinical Trials Office - Presbyterian - St. Luke's Medical Center	Ph:  303-839-6000
	Rose Medical Center
		Eduardo Pajon, MD	Ph:  303-777-2663
	St. Anthony Central Hospital
		Eduardo Pajon, MD	Ph:  303-777-2663
	St. Joseph Hospital
		Eduardo Pajon, MD	Ph:  303-777-2663
	Englewood
	Rocky Mountain Gynecologic Oncology
		Kevin Davis, MD	Ph:  303-781-9090
	Swedish Medical Center
		Eduardo Pajon, MD	Ph:  303-777-2663
	Fort Collins
	Front Range Cancer Specialists
		Diana Medgyesy, MD	Ph:  970-212-7600
	Poudre Valley Hospital
		Clinical Trials Office - Poudre Valley Hospital	Ph:  970-495-8226
	Grand Junction
	St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center
		Eduardo Pajon, MD	Ph:  303-777-2663
	Greeley
	North Colorado Medical Center
		Eduardo Pajon, MD	Ph:  303-777-2663
	Lone Tree
	Sky Ridge Medical Center
		Eduardo Pajon, MD	Ph:  303-777-2663
	Longmont
	Hope Cancer Care Center at Longmont United Hospital
		Eduardo Pajon, MD	Ph:  303-777-2663
	Loveland
	McKee Medical Center
		Eduardo Pajon, MD	Ph:  303-777-2663
	Pueblo
	St. Mary - Corwin Regional Medical Center
		Eduardo Pajon, MD	Ph:  303-777-2663
	Thornton
	North Suburban Medical Center
		Eduardo Pajon, MD	Ph:  303-777-2663
	Wheat Ridge
	Exempla Lutheran Medical Center
		Clinical Trials Office - Exempla Lutheran Medical Center	Ph:  303-403-3605
Connecticut
	Hartford
	Helen and Harry Gray Cancer Center at Hartford Hospital
		Clinical Trials Office - Helen and Harry Gray Cancer Center	Ph:  860-545-5363
	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
		Beth Nelson	Ph:  860-714-4680
	New Britain
	George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus
		Clinical Trials Office - George Bray Cancer Center	Ph:  860-224-5660
	New Haven
	Yale Cancer Center
		Clinical Trials Office - Yale Cancer Center	Ph:  203-785-5702
	Norwalk
	Norwalk Hospital
		Richard Frank, MD	Ph:  203-855-3517
	Stamford
	Carl and Dorothy Bennett Cancer Center at Stamford Hospital
		Clinical Trials Office - Carl and Dorothy Bennett Cancer Center	Ph:  203-323-8944
	Torrington
	Connecticut Oncology & Hematology - Torrington
		Michael Magnifico, MD	Ph:  860-482-5384
Delaware
	Lewes
	Tunnell Cancer Center at Beebe Medical Center
		Clinical Trials Office - Tunnell Cancer Center	Ph:  302-645-3171
	Newark
	CCOP - Christiana Care Health Services
		Clinical Trial Office - CCOP - Christiana Care Health Services	Ph:  302-733-6227
District of Columbia
	Washington