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 After Surgery in Treating Patients with Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Active 18 and over NCI GOG-0213 GOG-0213, NCT00565851

Special Category: NCI Web site featured trial

Objectives

Primary

1. To determine if surgical secondary cytoreduction in addition to adjuvant chemotherapy comprising carboplatin and paclitaxel with or without bevacizumab increases the duration of overall survival of patients with recurrent platinum-sensitive ovarian epithelial cancer, primary peritoneal cavity cancer, or fallopian tube cancer.
2. To determine if the addition of bevacizumab to the second-line and maintenance phases of treatment increases the duration of overall survival relative to second-line paclitaxel and carboplatin alone in these patients.

Secondary

1. To determine if the addition of bevacizumab to the second-line and maintenance phase of treatment increases the duration of progression-free survival relative to second-line paclitaxel and carboplatin alone in these patients.
2. To prospectively determine the incidence of carboplatin and paclitaxel hypersensitivity in these patients undergoing retreatment with both agents as first recurrence therapy.
3. To determine if surgical secondary cytoreduction in addition to adjuvant chemotherapy increases quality of life (QOL) of patients with recurrent platinum-sensitive ovarian epithelial cancer or primary peritoneal cavity cancer, as measured by the FACT-O trial outcome index and Rand SF-36 physical functioning scale.
4. To determine if the addition of bevacizumab to the second-line and maintenance phases of treatment increases QOL relative to second-line paclitaxel and carboplatin alone in patients with recurrent platinum-sensitive ovarian epithelial cancer or primary peritoneal cavity cancer.

Entry Criteria

Disease Characteristics:

• Patients must have histologic diagnosis of ovarian epithelial carcinoma, primary peritoneal cavity carcinoma, or fallopian tube carcinoma
  • Recurrent disease



• The following histologic epithelial cell types* are allowed:
  • Serous adenocarcinoma
  • Endometrioid adenocarcinoma
  • Mucinous adenocarcinoma
  • Undifferentiated carcinoma
  • Clear cell adenocarcinoma
  • Mixed epithelial carcinoma
  • Transitional cell carcinoma
  • Malignant Brenner Tumor
  • Adenocarcinoma not otherwise specified

   [Note: *Prior histologic diagnosis of borderline, low malignant potential (grade 0) epithelial carcinoma that was surgically resected and subsequently developed an unrelated, new invasive ovarian epithelial or primary peritoneal cavity cancer allowed provided the histological criteria for epithelial cell type is met]




• Patients with synchronous primary endometrial cancer or a past history of primary endometrial cancer are excluded, unless all of the following conditions are met:
  • Stage not greater than I-B
  • No more than superficial myometrial invasion
  • No vascular or lymphatic invasion
  • No poorly differentiated subtypes, including papillary serous, clear cell or other FIGO grade 3 lesions



• Patients must have had a complete response to front-line platinum-taxane therapy (at least 3 cycles) and a treatment-free interval without clinical evidence of progressive disease lasting at least 6 months
  • Front-line therapy may have included a biologic agent (e.g., bevacizumab) but an interval of at least 6 months must have elapsed after completion of therapy
  • A complete response to front-line chemotherapy must include the following:
    • Negative physical exam
    • Negative pelvic exam
    • Normalization of CA125, if elevated at baseline
    • Negative radiographic assessment of disease
  • Front-line treatment may include maintenance therapy following complete clinical or pathological response provided recurrent disease is not identified earlier than 6 months following completion of all anticancer treatment
  • Patients who have undergone reassessment laparotomy or laparoscopy following primary therapy are eligible provided they demonstrate a pathologic complete response based on the surgical assessment (i.e., all obtained specimens are histologically negative for disease)



• Clinically evident measurable or nonmeasurable disease defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded)
  • Each lesion must be ≥ 20 mm when measured by conventional techniques, MRI or CT scan, or ≥ 10 mm when measured by spiral CT scan
  • Nonmeasurable disease defined by symptomatic ascites or pleural effusion
  • Patients with clinically evident measurable or nonmeasurable disease must also have any 1 of the following:
    • CA-125 > 2 times upper limit of normal
    • Histologic confirmation of recurrence in the absence of an elevated CA-125 and measurable disease

Prior/Concurrent Therapy:

• See Disease Characteristics
• No prior adjuvant chemotherapy for localized breast cancer unless it was completed more than 5 years ago and the patient remains free of recurrent or metastatic disease
• No more than 1 prior regimen of chemotherapy (maintenance therapy is not considered a second regimen)
• No prior radiotherapy to any portion of the abdominal cavity or pelvis
• No prior chemotherapy for any other abdominal or pelvic tumor
• No major surgical procedure, open biopsy, or dental extractions or other dental surgery/procedure that results in an open wound within the past 28 days
• No placement of vascular access device or core biopsy within the past 7 days
• No concurrent immunotherapy or radiotherapy
• No anticipation of need for major surgical procedure during the course of the study

Patient Characteristics:

Inclusion criteria:

• GOG performance status of 0, 1, or 2
• Platelet count ≥ 100,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Creatinine ≤ 1.5 mg/dL (133 < mol/L) OR creatinine clearance ≥ 60 mL/min
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• SGOT/AST and alkaline phosphatase ≤ 2.5 times ULN (< 5.0 times ULN in the presence of liver metastasis)
• Urine protein-to-creatinine ratio < 1.0 mg/dL
• Signed an approved informed consent and authorization permitting release of personal health information
• Patients with allergic (i.e., hypersensitivity) reactions to these chemotherapeutic agents are eligible if they were successfully retreated following a desensitization program or protocol

Exclusion criteria:

• Patients who require parenteral hydration or nutrition and have evidence of partial bowel obstruction or perforation
• Patients with uncontrolled infection
• Patients with concurrent severe medical problems unrelated to the malignancy that would significantly limit full compliance with the study or expose the patient to extreme risk or decreased life expectancy
• Patients with peripheral neuropathy ≥ grade 2
• Patients with a history of allergic reactions to carboplatin and/or paclitaxel or chemically similar compounds
• Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
• Patients of childbearing potential not practicing adequate contraception or patients who are pregnant or nursing
• Patients with other invasive malignancies, with the exception of nonmelanoma skin cancer, or patients who had (or have) any evidence of the other cancer present within the past 5 years or whose previous cancer treatment contraindicates this protocol therapy
• Patients with active bleeding or pathologic conditions that carry high risk of bleeding such as a known bleeding disorder, coagulopathy, or tumor involving major vessels
• Patients with a history or evidence upon physical examination of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or a history of stroke within the past 5 years
• Patients with clinically significant cardiovascular disease including any of the following:
  • Significant cardiac conduction abnormalities (e.g., PR interval > 0.24 sec or 2nd or 3rd degree atrioventricular block)
  • Uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg or diastolic BP > 90 mm Hg
  • Myocardial infarction, cardiac arrhythmia, or unstable angina within the past 6 months
  • New York Heart Association grade II or greater congestive heart failure
  • Serious cardiac arrhythmia requiring medication
  • Grade II or greater peripheral vascular disease unless (<24 hrs) episodes of ischemia managed non-surgically and without permanent deficit
  • History of cerebrovascular accident within the past 6 months
  • No significant traumatic injury within the past 28 days

Expected Enrollment

Outcomes

Overall survival

Progression-free survival
Frequency and severity of adverse events

Outline

This is a multicenter study. Patients are assigned to 1 of 2 treatment groups. Patients who are not candidates for surgical cytoreduction (i.e., those for whom complete cytoreduction in the estimation of the investigator is impossible or a medical infirmity precludes exploration and debulking) are eligible to receive chemotherapy after randomization. Patients who are eligible for surgery undergo abdominal exploration with cytoreduction and undergo tumor tissue collection and complete a quality of life questionnaire before and after surgery. All patients are then randomized to 1 of 2 treatment arms.

• Arm I: Patients receive paclitaxel IV over 3 hours or docetaxel IV over 1 hour and carboplatin over 30 minutes on day 1.



• Arm II: Patients receive chemotherapy as in arm I and bevacizumab IV over 30-90 minutes on day 1.

Treatment in both arms repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients with measurable disease achieving a clinical response (CR) receive 6-8 courses of therapy. Patients with stable disease or partial regression receive a maximum of 6 courses. Patients without measurable lesions as determined by a CT scan prior to initiating study treatment continue therapy for 6 courses or, if CA-125 normalizes, for 2 cycles beyond CA-125 normalization, whichever is greater. Patients in arm II then receive a maintenance regimen comprising bevacizumab IV over 30-90 minutes. Treatment with bevacizumab alone repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 10 years.

Trial Contact Information

Trial Lead Organizations

Gynecologic Oncology Group

Robert Coleman, MD, Protocol chair		Ph: 713-745-3357; 800-392-1611 Email: rcoleman@mdanderson.org
Scott Eisenkop, MD, FACOG, Protocol co-chair		Ph: 408-378-6131
Deborah Armstrong, MD, Protocol co-chair		Ph: 410-614-2743 Email: darmstro@jhmi.edu
Thomas Herzog, MD, Protocol co-chair		Ph: 212-305-3410
Paul Sabbatini, MD, Protocol co-chair		Ph: 212-639-6423; 800-525-2225

U.S.A.
Alaska
	Anchorage
	Providence Cancer Center
		Clinical Trials Office - Providence Cancer Center	Ph:  907-261-3109
California
	Burbank
	Providence Saint Joseph Medical Center - Burbank
		Clinical Trials Office - Providence Saint Joseph Medical Center - Burbank	Ph:  818-847-3220
	Long Beach
	Todd Cancer Institute at Long Beach Memorial Medical Center
		Krishnansu Tewari	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:  323-783-4018
	Orange
	Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
		Clinical Trials Office - Chao Family Comprehensive Cancer Center	Ph:  877-UC-STUDY
			Email: ucstudy@uci.edu
	San Francisco
	UCSF Helen Diller Family Comprehensive Cancer Center
		Clinical Trials Office - UCSF Helen Diller Family Comprehensive Cancer Center	Ph:  877-827-3222
Colorado
	Aurora
	Colorado Gynecologic Oncology Group, PC
		Susan Davidson, MD	Ph:  303-315-7897
Connecticut
	Hartford
	Helen and Harry Gray Cancer Center at Hartford Hospital
		Clinical Trials Office - Helen and Harry Gray Cancer Center	Ph:  860-545-5363
	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
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
	Washington Cancer Institute at Washington Hospital Center
		Clinical Trials Office - Washington Cancer Institute	Ph:  202-877-8839
Florida
	Fort Myers
	Florida Gynecologic Oncology - Fort Myers
		Edward Grendys, MD	Ph:  239-992-0077
	Miami
	University of Miami Sylvester Comprehensive Cancer Center - Miami
		University of Miami Sylvester Comprehensive Cancer Center Clinical Trial Matching Service	Ph:  866-574-5124
			Email: Sylvester@emergingmed.com
	Saint Petersburg
	Bayfront Cancer Care Center at Bayfront Medical Center
		James LaPolla, MD	Ph:  727-821-9688
Georgia
	Macon
	Central Georgia Gynecologic Oncology
		Gary Eddy, MD	Ph:  476-633-6090
	Savannah
	Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
		Clinical Trials Office - Curtis and Elizabeth Anderson Cancer Institute	Ph:  912-350-8568
Illinois
	Arlington Heights
	Northwest Community Hospital
		Josh Tunca, MD	Ph:  847-358-2009
	Aurora
	Rush-Copley Cancer Care Center
		Kendrith Rowland, MD	Ph:  217-383-3019
	Chicago
	Robert H. Lurie Comprehensive Cancer Center at Northwestern University
		Clinical Trials Office - Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Ph:  312-695-1301
			Email: cancer@northwestern.edu
	Rush University Medical Center
		Clinical Trials Office - Rush University Medical Center	Ph:  312-942-5498
			Email: clinical_trials@rush.edu
	University of Chicago Cancer Research Center
		Clinical Trials Office - University of Chicago Cancer Research Center	Ph:  773-834-7424
	University of Illinois Cancer Center
		Clinical Trial Office - University of Illinois Cancer Center	Ph:  312-355-3046
	Hinsdale
	Hinsdale Hematology Oncology Associates
		Sudarshan Sharma, MD	Ph:  630-856-6757
	Joliet
	Joliet Oncology-Hematology Associates, Limited - West
		Kendrith Rowland, MD	Ph:  217-383-3019
	Palatine
	Chicago Gynecologic Oncology, SC
		Josh Tunca, MD	Ph:  847-358-2009
	Springfield
	Regional Cancer Center at Memorial Medical Center
		Clinical Trials Office - Regional Cancer Center at Memorial Medical Center	Ph:  217-788-4233
	Urbana
	Carle Cancer Center at Carle Foundation Hospital
		Clinical Trials Office - Carle Cancer Center	Ph:  800-446-5532
	CCOP - Carle Cancer Center
		Clinical Trials Office - CCOP - Carle Cancer Center	Ph:  800-446-5532
Indiana
	Elkhart
	Elkhart General Hospital
		Michael Rodriguez	Ph:  574-294-2621
	Indianapolis
	St. Vincent Indianapolis Hospital
		Clinical Trials Office - St. Vincent Indianapolis Hospital	Ph:  317-338-2194
	Kokomo
	Howard Community Hospital
		Michael Rodriguez	Ph:  765-453-8571
	Michigan City
	Saint Anthony Memorial Health Centers
		Kendrith Rowland, MD	Ph:  217-383-3019
	Munster
	Community Hospital
		Erwin Robin, MD	Ph:  219-836-2860
	South Bend
	CCOP - Northern Indiana CR Consortium
		Michael Rodriguez	Ph:  574-647-7370 800-284-7370
	Memorial Hospital of South Bend
		Clinical Trials Office - Memorial Hospital of South Bend	Ph:  800-284-7370
	Saint Joseph Regional Medical Center
		Michael Rodriguez	Ph:  574-237-7111
Iowa
	Iowa City
	Holden Comprehensive Cancer Center at University of Iowa
		Cancer Information Service	Ph:  800-237-1225
Louisiana
	Baton Rouge
	Woman's Hospital
		Giles Fort, MD	Ph:  225-358-1071
Maryland
	Baltimore
	Harry & Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center
		Clinical Trials Office - Harry & Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center	Ph:  443-777-7364
	Elkton MD
	Union Hospital Cancer Program at Union Hospital
		Mark Borowsky	Ph:  410-398-4000
Massachusetts
	Worcester
	UMASS Memorial Cancer Center - University Campus
		Susan Zweizig, MD	Ph:  508-334-1160
Michigan
	Ann Arbor
	CCOP - Michigan Cancer Research Consortium
		Angela Kueck	Ph:  877-590-5995
	Saint Joseph Mercy Cancer Center
		Angela Kueck	Ph:  734-712-5658 888-474-4673
	University of Michigan Comprehensive Cancer Center
		Clinical Trials Office - University of Michigan Comprehensive Cancer Center	Ph:  800-865-1125
	Battle Creek
	Battle Creek Health System Cancer Care Center
		Marianne Lange, MD	Ph:  616-977-6243
	Big Rapids
	Mecosta County Medical Center
		Marianne Lange, MD	Ph:  616-977-6243
	Detroit
	Barbara Ann Karmanos Cancer Institute
		Clinical Trials Office - Barbara Ann Karmanos Cancer Institute	Ph:  313-576-9363
	Escanaba
	Green Bay Oncology, Limited - Escanaba
		Jonathan Tammela	Ph:  800-432-6049
	Grand Rapids
	Butterworth Hospital at Spectrum Health
		Marianne Lange, MD	Ph:  616-977-6243
	CCOP - Grand Rapids
		Marianne Lange, MD	Ph:  616-977-6243
	Gynecologic Oncology of West Michigan
		Gordon Downey, MD	Ph:  616-957-3398
	Lacks Cancer Center at Saint Mary's Health Care
		Marianne Lange, MD	Ph:  616-977-6243
	Grosse Pointe Woods
	Van Elslander Cancer Center at St. John Hospital and Medical Center
		Clincial Trials Office - Van Elslander Cancer Center at St. John Hospital and Medical Center	Ph:  313-343-3166
	Holland
	Holland Community Hospital
		Marianne Lange, MD	Ph:  616-977-6243
	Iron Mountain
	Dickinson County Healthcare System
		Jonathan Tammela	Ph:  906-774-1313
	Muskegon
	Hackley Hospital
		Marianne Lange, MD	Ph:  616-977-6243
	Petoskey
	Northern Michigan Hospital
		Marianne Lange, MD	Ph:  616-977-6243
	Royal Oak
	William Beaumont Hospital - Royal Oak Campus
		Clinical Trials Office - William Beaumont Hospital - Royal Oak Campus	Ph:  248-551-7695
	St. Joseph
	Lakeland Regional Cancer Care Center - St. Joseph
		Michael Rodriguez	Ph:  269-983-8698 800-303-8399
	Traverse City
	Munson Medical Center
		Marianne Lange, MD	Ph:  616-977-6243
	Wyoming
	Metro Health Hospital
		Marianne Lange, MD	Ph:  616-977-6243
Minnesota
	Burnsville
	Fairview Ridges Hospital
		Patrick Flynn, MD	Ph:  612-863-8585
	Coon Rapids
	Mercy and Unity Cancer Center at Mercy Hospital
		Patrick Flynn, MD	Ph:  612-863-8585
	Duluth
	St. Luke's Hospital Cancer Care Center
		Tanya Repka, MD, FACP	Ph:  218-726-3081
	Edina
	Fairview Southdale Hospital
		Clinical Trials Office - Fairview Southdale Hospital	Ph:  612-625-3650
	Fridley
	Mercy and Unity Cancer Center at Unity Hospital
		Patrick Flynn, MD	Ph:  612-863-8585
	Maplewood
	Minnesota Oncology Hematology, PA - Maplewood
		Patrick Flynn, MD	Ph:  612-863-8585
	Minneapolis
	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
		Clinical Trials Office - Virginia Piper Cancer Institute	Ph:  612-863-5654
	Robbinsdale
	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
		Clinical Trials Office - Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Ph:  763-520-1893
	Saint Louis Park
	CCOP - Metro-Minnesota
		Patrick Flynn, MD	Ph:  612-863-8585
	Park Nicollet Cancer Center
		Patrick Flynn, MD	Ph:  612-863-8585
	Saint Paul
	United Hospital
		Patrick Flynn, MD	Ph:  612-863-8585