Carboplatin, Paclitaxel, Bevacizumab, and Veliparib in Treating Patients With Newly Diagnosed Stage II-IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer

Primary Peritoneal Carcinoma Clinical Trial

Official title:

A Phase I Study of Intravenous Carboplatin/Paclitaxel or Intravenous and Intraperitoneal Paclitaxel/Cisplatin in Combination With Continuous or Intermittent /CTEP-Supplied Agent ABT-888 (NSC #737664) and CTEP-Supplied Agent Bevacizumab (NSC #704865) in Newly Diagnosed Patients With Previously Untreated Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00989651
• Other study ID #: NCI-2011-03730
• Secondary ID: NCI-2011-03730GO
• Status: Completed
• Phase: Phase 1
• Start date: October 28, 2009
• Est. completion date: April 10, 2020

Study information

• Verified date: October 2021
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase I trial studies the side effects and best dose of veliparib when given together with carboplatin, paclitaxel, and bevacizumab in treating patients with newly diagnosed stage II-IV ovarian epithelial, fallopian tube, or primary peritoneal cancer. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cells to repair themselves from damage and survive. 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, by stopping them from dividing, or by stopping them from spreading. Bevacizumab, a type of drug called a monoclonal antibody, blocks tumor growth by targeting certain cells and preventing the growth of new blood vessels that tumors need to grow. Giving veliparib together with carboplatin, paclitaxel, and bevacizumab may kill more tumor cells.

Description:

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) and dose-limiting toxicities of ABT-888 (veliparib) when administered using continuous versus intermittent dosing schedules with intravenous carboplatin, paclitaxel and bevacizumab using two different treatment regimens; or with intraperitoneal cisplatin and intravenous and intraperitoneal paclitaxel and bevacizumab in women with newly diagnosed, previously untreated, epithelial ovarian, fallopian tube, or primary peritoneal cancer.

II. To determine the feasibility of these treatment regimens over four cycles in a 2-stage group sequential design once the MTD is established.

III. To assess the toxicity of these regimens using Cancer Therapy Evaluation Program (CTEP) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

SECONDARY OBJECTIVES:

I. To estimate the response rate (in measurable disease patients) and progression-free survival in patients treated with these treatment regimens.

TERTIARY OBJECTIVES:

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

II. To assess genomic breast cancer, early onset (BRCA) mutation status in all patients in regimens I and II with continuous ABT-888 dosing and descriptively correlate with toxicity and efficacy.

OUTLINE: This is a dose-escalation study of veliparib followed by a feasibility study. Patients are sequentially assigned to 1 of 3 treatment regimens.

REGIMEN I: Patients receive paclitaxel intravenously (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 veliparib orally (PO) twice daily (BID) 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 veliparib 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.

REGIMEN III: Patients receive paclitaxel IV over 3 hours on day 1 and intraperitoneally (IP) on day 8, and cisplatin IP on day 1 or 2. Patients also receive bevacizumab and veliparib as in Regimen I. Treatment repeats every 21 days for 6 courses. Patients then receive bevacizumab alone on day 1. Treatment repeats every 21 days for 16 courses in the absence of disease progression or unacceptable toxicity.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 431
• Est. completion date: April 10, 2020
• Est. primary completion date: September 2, 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with a histologic diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, or carcinosarcoma stage II, III, or IV with either optimal (=< 1 cm residual disease) or suboptimal residual disease

• All patients must have a procedure for determining diagnosis of epithelial ovarian, fallopian tube, primary peritoneal, or carcinosarcoma with appropriate tissue for histologic evaluation

• Patients with the following histologic cell types are eligible:

• Serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial adenocarcinoma, transitional cell carcinoma, malignant Brenner's tumor, adenocarcinoma not otherwise specified (N.O.S.) or carcinosarcoma

• Absolute neutrophil count (ANC) greater than or equal to 1,500/mm^3, equivalent to CTEP Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, grade 1; this ANC cannot have been induced or supported by granulocyte colony stimulating factors

• Platelets greater than or equal to 100,000/mm^3

• Regimens I and II: Creatinine =< 1.5 x institutional upper limit normal (ULN), CTCAE grade 1

• Regimen III: Creatinine no greater than the institutional upper limits of normal

• Bilirubin less than or equal to 1.5 x ULN (CTEP CTCAE version 4.0, grade 1)

• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) less than or equal to 3 x ULN (CTEP CTCAE version 4.0, grade 1)

• Alkaline phosphatase less than or equal to 2.5 x ULN (CTEP CTCAE version 4.0, grade 1)

• Albumin greater than or equal to 3.0 g/dL

• Neuropathy (sensory and motor) less than or equal to CTEP CTCAE version 4.0, grade 1

• Prothrombin time (PT) such that international normalized ratio (INR) is =< 1.5 x ULN (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a partial thromboplastin time (PTT) < 1.5 x ULN

• Patients must have a Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2

• Patients must be entered between 1 and 12 weeks after initial surgery performed for the combined purpose of diagnosis, staging and cytoreduction

• Patients who have met the pre-entry requirements specified

• Patients must have signed an approved informed consent and authorization permitting release of personal health information

Exclusion Criteria:

• Patients with a current diagnosis of borderline epithelial ovarian tumor (formerly "tumors of low malignant potential") or recurrent invasive epithelial ovarian, primary peritoneal or fallopian tube cancer treated with surgery only (such as patients with stage IA or IB low-grade epithelial ovarian or fallopian tube cancers) are not eligible

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

• Patients with synchronous primary endometrial cancer or a past history of endometrial cancer, unless all of the following conditions are met:

• Stage not greater than IB

• No more than superficial myometrial invasion

• No vascular or lymphatic invasion

• No poorly differentiated subtypes, including papillary serous, clear cell, or other International Federation of Gynecology and Obstetrics (FIGO) grade 3 lesions

• Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies as noted, are excluded if there is any evidence of other malignancy being present within the last five years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy

• Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease

• Patients who have received prior chemotherapy for any abdominal or pelvic tumor within the last five years are excluded; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease

• Patients with acute hepatitis or active infection that requires parenteral antibiotics

• Patients with serious non-healing wound, ulcer, or bone fracture; this includes history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days; patients with granulating incisions healing by secondary intention with no evidence of fascial dehiscence or infection are eligible but require weekly wound examinations

• Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels

• Patients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures or history of seizures, and/or any CNS metastases are ineligible

• Patients with history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of treatment on this study are ineligible

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

• Myocardial infarction or unstable angina < 6 months prior to registration

• New York Heart Association (NYHA) class II or higher congestive heart failure

• Serious cardiac arrhythmia requiring medication

• CTEP CTCAE version 4.0, grade 2 or higher peripheral ischemia (brief [< 24 hours (hrs)] episode of ischemia managed non-surgically and without permanent deficit)

• Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies

• Patients with clinically significant proteinuria (urine protein creatinine ratio greater or equal to 1.0)

• Patients with invasive procedures or anticipation of invasive procedures within the following timeframes as defined below:

• Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to the first date of bevacizumab therapy (cycle 2)

• Major surgical procedure anticipated during the course of the study

• Core biopsy within 7 days prior to the first date of bevacizumab therapy (cycle 2)

• Patients who are pregnant or nursing

• Patients with clinical symptoms or signs of gastrointestinal obstruction and who require parenteral hydration or nutrition

• Patients with GOG performance status of 3 or 4

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma, Mucinous
• Brenner Tumor
• Carcinoma
• Carcinoma, Endometrioid
• Carcinoma, Ovarian Epithelial
• Carcinoma, Transitional Cell
• Carcinosarcoma
• Cystadenocarcinoma
• Fallopian Tube Carcinoma
• Fallopian Tube Carcinosarcoma
• Fallopian Tube Clear Cell Adenocarcinoma
• Fallopian Tube Endometrioid Adenocarcinoma
• Fallopian Tube Mucinous Adenocarcinoma
• Fallopian Tube Neoplasms
• Fallopian Tube Serous Neoplasm
• Fallopian Tube Transitional Cell Carcinoma
• Fallopian Tube Undifferentiated Carcinoma
• Mixed Tumor, Mullerian
• Ovarian Brenner Tumor
• Ovarian Carcinoma
• Ovarian Carcinosarcoma
• Ovarian Clear Cell Adenocarcinoma
• Ovarian Endometrioid Adenocarcinoma
• Ovarian Mucinous Adenocarcinoma
• Ovarian Neoplasms
• Ovarian Seromucinous Tumor
• Ovarian Serous Adenocarcinoma
• Ovarian Transitional Cell Carcinoma
• Ovarian Undifferentiated Carcinoma
• Peritoneal Neoplasms
• Primary Peritoneal Carcinoma
• Primary Peritoneal Serous Adenocarcinoma
• Stage IIA Fallopian Tube Cancer AJCC v6 and v7
• Stage IIA Ovarian Cancer AJCC V6 and v7
• Stage IIB Fallopian Tube Cancer AJCC v6 and v7
• Stage IIB Ovarian Cancer AJCC v6 and v7
• Stage IIC Fallopian Tube Cancer AJCC v6 and v7
• Stage IIC Ovarian Cancer AJCC v6 and v7
• Stage IIIA Fallopian Tube Cancer AJCC v7
• Stage IIIA Ovarian Cancer AJCC v6 and v7
• Stage IIIA Primary Peritoneal Cancer AJCC v7
• Stage IIIB Fallopian Tube Cancer AJCC v7
• Stage IIIB Ovarian Cancer AJCC v6 and v7
• Stage IIIB Primary Peritoneal Cancer AJCC v7
• Stage IIIC Fallopian Tube Cancer AJCC v7
• Stage IIIC Ovarian Cancer AJCC v6 and v7
• Stage IIIC Primary Peritoneal Cancer AJCC v7
• Stage IV Fallopian Tube Cancer AJCC v6 and v7
• Stage IV Ovarian Cancer AJCC v6 and v7
• Stage IV Primary Peritoneal Cancer AJCC v7

Intervention

Biological:
• Bevacizumab
Given IV

Drug:
• Carboplatin
Given IV
• Cisplatin
Given IP

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Paclitaxel
Given IV or IP
• Veliparib
Given PO

Locations

Country	Name	City	State
United States	Augusta University Medical Center	Augusta	Georgia
United States	University of Colorado Hospital	Aurora	Colorado
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	MedStar Franklin Square Medical Center/Weinberg Cancer Institute	Baltimore	Maryland
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Women and Infants Hospital	Providence	Rhode Island
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	NRG Oncology

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in PARP inhibition in PBMCs	PARP inhibition in PBMCs in each course (courses 1 and 2) and the change from course1 to course 2 will be summarized by dose level and regimen using descriptive statistics (e.g., mean, standard deviation, median, quartiles) and using graphs. In addition, linear models may be used to assess the association between PARP inhibition and dose level with transformations of the PARP inhibition as appropriate.	Day 1 to day 22 (day 1 of course 1 to day 1 of course 2)
Other	Genomic BRCA mutation status		Baseline
Primary	Incidence of dose-limiting toxicities (DLTs) occurring in the first or second course of treatment (dose-escalation phase)		Up to day 42
Primary	Incidence of DLTs occurring in the first 4 courses of treatment (feasibility phase)		Up to day 84
Secondary	Objective tumor response (complete and partial response) as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)	Tabulated by regimen and BRCA mutation status.	Up to 11 years
Secondary	Progression-free survival	Summarized using Kaplan-Meier plots by BRCA mutation status.	Time from start of treatment to time of progression or death, assessed up to 11 years
Secondary	Incidence of toxicity, graded according to National Cancer Institute CTCAE version 4.0	Tabulated by regimen and by BRCA mutation status.	Up to 30 days after last dose of treatment