Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

This phase I trial is studying the side effects and best dose of ABT-888 when given together with carboplatin, paclitaxel, and bevacizumab in treating patients with newly diagnosed stage II, stage III, or stage IV ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may stop the growth of tumor cells by blocking blood flow to the tumor. ABT-888 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving carboplatin, paclitaxel, and bevacizumab together with ABT-888 may kill more tumor cells

Further Study Information

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) and dose-limiting toxicities of ABT-888 when administered with carboplatin, paclitaxel, and bevacizumab using 2 different treatment regimens in patients with newly diagnosed stage II-IV ovarian epithelial, fallopian tube, or primary peritoneal cancer.

II. To determine the feasibility of these regimens over 4 courses once the MTD is established.

III. To assess the toxicity of these regimens using NCI CTCAE v4.0 criteria.

SECONDARY OBJECTIVES:

I. To estimate the response rate in patients with measurable disease. II. To estimate the progression-free survival of patients treated with these regimens.

III. To assess the extent of poly-ADP-ribose polymerase (PARP) inhibition in peripheral blood mononuclear cells on day 1 of courses 1 and 2.

IV. To assess genomic BRCA mutation status in all patients and descriptively correlate it with toxicity and efficacy.

OUTLINE: This is a multicenter, dose-escalation study of ABT-888 followed by a feasibility study. Patients are sequentially assigned to 1 of 2 treatment regimens.

REGIMEN I: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes (beginning in course 2) on day 1. Patients also receive oral ABT-888 twice daily on days 1-21. Treatment repeats every 21 days for 6 courses. Patients then receive bevacizumab alone on day 1. Treatment with bevacizumab repeats every 21 days for 16 courses in the absence of disease progression or unacceptable toxicity.

REGIMEN II: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15. Patients also receive carboplatin, bevacizumab, and ABT-888 as in regimen I. Treatment repeats every 21 days for 6 courses. Patients then receive bevacizumab alone on day 1. Treatment with bevacizumab repeats every 21 days for 16 courses in the absence of disease progression or unacceptable toxicity. Blood samples are collected periodically for biomarker analysis.

After completion of study treatment, patients are followed up periodically.

Eligibility Criteria

Inclusion Criteria:

• Histologically confirmed newly diagnosed ovarian epithelial, fallopian tube, or primary peritoneal carcinoma, including one of the following histologic cell types:

• Serous adenocarcinoma

• Endometrioid adenocarcinoma

• Mucinous adenocarcinoma

• Undifferentiated carcinoma

• Clear cell adenocarcinoma

• Mixed epithelial adenocarcinoma

• Transitional cell carcinoma

• Malignant Brenner tumor

• Adenocarcinoma not otherwise specified

• Carcinosarcoma

• Stage II-IV disease defined surgically with either optimal (≤ 1 cm) or suboptimal residual disease

• Has undergone initial surgery for diagnosis, staging, and cytoreduction within the past 1-12 weeks

• No current diagnosis of borderline ovarian epithelial tumor (formerly "tumors of low malignant potential") or recurrent invasive ovarian epithelial, primary peritoneal, or fallopian tube cancer treated with surgery only (e.g., stage IA or IB low-grade ovarian epithelial or fallopian tube cancers)

• Patients with a prior diagnosis of a borderline tumor that was surgically resected and who subsequently developed an unrelated, new invasive ovarian epithelial, primary peritoneal, or fallopian tube cancer are eligible provided they have not received prior chemotherapy for any ovarian tumor

• No prior or synchronous primary endometrial cancer, unless all of the following criteria are met:

• Disease stage ≤ IB

• 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

• No history or evidence of primary brain tumor or brain metastases by physical exam

• GOG performance status 0-2

• ANC ≥ 1,500/mm^3 (not induced or supported by granulocyte colony-stimulating factors)

• Platelet count ≥ 100,000/mm^3

• Creatinine ≤ 1.5 times upper limit of normal (ULN)

• Bilirubin ≤ 1.5 times ULN

• SGOT ≤ 2.5 times ULN

• Alkaline phosphatase ≤ 2.5 times ULN

• Albumin ≥ 3.0 g/dL

• PT/INR ≤ 1.5 (or an in-range INR, usually between 2 and 3, if patient is on a stable dose of therapeutic warfarin)

• PTT < 1.5 times ULN

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 3 months after completion of study treatment

• No clinically significant proteinuria (i.e., urine protein:creatinine ratio ≥ 1.0)

• No neuropathy (sensory and motor) > CTCAE grade 1

• No acute hepatitis or active infection requiring parenteral antibiotics

• No serious non-healing wound, ulcer, or bone fracture

• Patients with granulating incisions healing by secondary intention are eligible provided there is no evidence of fascial dehiscence or infection and the patient undergoes weekly wound examinations

• No abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within the past 28 days

• No clinical symptoms or signs of GI obstruction and/or requirement for parenteral hydration or nutrition

• No active bleeding or pathologic condition that carries a high risk of bleeding (e.g., known bleeding disorder, coagulopathy, or tumor involving major vessels)

• No clinically significant cardiovascular disease, including any of the following:

• Uncontrolled hypertension, defined as systolic BP > 150 mm Hg or diastolic BP > 90 mm Hg

• Myocardial infarction or unstable angina within the past 6 months

• NYHA class II-IV congestive heart failure

• Serious cardiac arrhythmia requiring medication

• Peripheral ischemia ≥ CTCAE grade 2 (at least brief [< 24 hours] episodes of ischemia managed non-surgically and without permanent deficit)

• No cerebrovascular accident, transient ischemic attack, or subarachnoid hemorrhage within the past 6 months

• No seizures not controlled with standard medical therapy or other evidence of CNS disease by physical exam

• No other invasive malignancies within the past 5 years, except for nonmelanoma skin cancer and localized cancer of the breast or head and neck

• No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies

• No significant traumatic injury within the past 28 days

• See Disease Characteristics

• No prior cancer treatment that would contraindicate study therapy

• More than 5 years since prior chemotherapy for any abdominal or pelvic tumor

• Prior adjuvant chemotherapy for localized breast cancer is allowed provided it was completed > 3 years ago AND the patient remains free of recurrent or metastatic disease

• No prior radiotherapy to any portion of the abdominal cavity or pelvis

• Prior radiotherapy for localized cancer of the breast, head and neck, or skin is allowed provided it was completed > 3 years ago AND the patient remains free of recurrent or metastatic disease

• More than 28 days since prior major surgical procedure or open biopsy

• More than 7 days since prior core biopsy

• No concurrent major surgical procedure

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

Katherine Bell-McGuinn

Principal Investigator

U.S.A.
Colorado
	Aurora
	University of Colorado Cancer Center at UC Health Sciences Center
		Susan Davidson	Ph: 720-848-0650
Georgia
	Augusta
	Medical College of Georgia Cancer Center
		Sharad Anant Ghamande	Ph: 706-721-1663
			Email: cancer@georgiahealth.edu
Illinois
	Chicago
	University of Chicago Cancer Research Center
		Seiko Diane Yamada	Ph: 773-834-7424
Iowa
	Iowa City
	Holden Comprehensive Cancer Center at University of Iowa
		Koen De Geest	Ph: 800-237-1225
Maryland
	Baltimore
	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
		Deborah K. Armstrong	Ph: 410-955-8804
			Email: jhcccro@jhmi.edu
Missouri
	Saint Louis
	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
		David Gardner Mutch	Ph: 800-600-3606
			Email: info@ccadmin.wustl.edu
New York
	New York
	Memorial Sloan-Kettering Cancer Center
		Katherine M Bell-McGuinn	Ph: 212-639-7202
Ohio
	Cleveland
	Case Comprehensive Cancer Center
		Steven E. Waggoner	Ph: 800-641-2422
	Cleveland Clinic Taussig Cancer Center
		Steven E. Waggoner	Ph: 800-641-2422
	Mayfield Heights
	Hillcrest Cancer Center at Hillcrest Hospital
		Steven E. Waggoner	Ph: 800-641-2422
Oklahoma
	Oklahoma City
	Oklahoma University Cancer Institute
		Robert S. Mannel	Ph: 405-271-4272
			Email: julie-traylor@ouhsc.edu
Pennsylvania
	Philadelphia
	Fox Chase Cancer Center - Philadelphia
		Lainie P Martin	Ph: 215-728-4790
	Gynecologic Oncology Group
		Katherine M Bell-McGuinn	Ph: 212-639-7202
Rhode Island
	Providence
	Women and Infants Hospital of Rhode Island
		Carolyn K McCourt	Ph: 401-274-1122
Virginia
	Charlottesville
	University of Virginia Cancer Center
		Linda R. Duska	Ph: 434-243-6143
	Richmond
	Virginia Commonwealth University Massey Cancer Center
		Andrew Poklepovic	Ph: 804-628-1939

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00989651
Information obtained from ClinicalTrials.gov on April 04, 2013

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