A Phase I Trial of Pegylated Liposomal Doxorubicin (PLD), Carboplatin and NCI Supplied Veliparib (ABT-888), and NCI Supplied Bevacizumab in Recurrent Platinum Sensitive Ovarian, Primary Peritoneal and Fallopian Tube Cancer

National Cancer Institute (NCI)13 sites in 1 country41 target enrollmentStarted: October 11, 2011Last updated: July 22, 2019

ConditionsOvarian Clear Cell Cystadenocarcinoma Ovarian Endometrioid Adenocarcinoma Ovarian Seromucinous Carcinoma Ovarian Serous Cystadenocarcinoma Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma Undifferentiated Ovarian Carcinoma

InterventionsBevacizumab Carboplatin Laboratory Biomarker Analysis Pegylated Liposomal Doxorubicin Hydrochloride Veliparib

DrugsCarboplatin Pegylated Liposomal Doxorubicin Hydrochloride Veliparib

Overview

Phase: Phase 1
Status: Completed
Sponsor: National Cancer Institute (NCI)
Enrollment: 41
Locations: 13
Primary Endpoint: Dose-limiting toxicity (DLT), assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4

Overview Study Design Eligibility Criteria Arms & Interventions Outcomes Investigators Sites Records & Identifiers Similar Trials

Overview

Brief Summary

This phase I trial studies the side effects and the best dose of veliparib when given together with pegylated liposomal doxorubicin hydrochloride, carboplatin, and bevacizumab in treating patients with ovarian cancer, primary peritoneal cancer, or fallopian tube cancer that has returned after previous treatment. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as pegylated liposomal doxorubicin hydrochloride and carboplatin, may stop the growth of tumor cells by, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab, can block tumor growth by blocking the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of tumors by blocking the growth of new blood vessels necessary for tumor growth. Giving veliparib together with pegylated liposomal doxorubicin hydrochloride, carboplatin, and bevacizumab may kill more tumor cells.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the maximum-tolerated doses (MTD) and dose-limiting toxicities of two different regimens of ABT-888 (veliparib) when administered with carboplatin and PLD (Doxil, Lipodox) (pegylated liposomal doxorubicin hydrochloride) in recurrent, platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer.

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

III. To examine the tolerability of these treatment regimens in combination with bevacizumab at the MTD.

SECONDARY OBJECTIVES:

I. To estimate the objective response rate (complete and partial) in patients with measurable disease.

TERTIARY OBJECTIVES:

I. To examine the relationships between platinum-free interval, activity of ABT-888 (objective response rate) and measures of breast cancer susceptibility gene 1/2 (BRCA1/2) status including mutations, alterations, rearrangements, promoter methylation, and immunohistochemical expression).

OUTLINE: This is a dose-escalation study of veliparib. Patients are assigned to 1 of 2 treatment arms.

REGIMEN I: Patients receive veliparib orally (PO) twice daily (BID) on days 1-7, and pegylated liposomal doxorubicin hydrochloride intravenously (IV) over 1 hour and carboplatin IV over 30 minutes on day 1.

REGIMEN II: Patients receive veliparib PO BID on days 1-28, and pegylated liposomal doxorubicin hydrochloride and carboplatin as in Regimen I.

BEVACIZUMAB: Once the MTD for veliparib has been determined, patients also receive bevacizumab IV over 30-90 minutes on days 1 and 15.

In both arms, treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up quarterly for 1 year.

Study Design

Study Type: Interventional
Allocation: Non Randomized
Intervention Model: Parallel
Primary Purpose: Treatment
Masking: None

Eligibility Criteria

Ages: 18 Years to — (Adult, Older Adult)
Sex: Female
Accepts Healthy Volunteers: No

Inclusion Criteria

•Patients must have histologic diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal carcinoma which is now recurrent; histologic documentation of the original primary tumor is required via the pathology report
•Patients with the following histologic epithelial cell types are eligible: high-grade serous adenocarcinoma, endometrioid adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma or adenocarcinoma not otherwise specified (N.O.S.)
•Patients must have recurrence documented by elevated cancer antigen (CA)-125 (biochemical recurrence) or clinically evident measurable or non-measurable recurrent disease
•Biochemical recurrence is defined as a CA-125 greater than or equal to two times the upper normal limit; patients whose CA-125 is less than 100 U/mL must undergo a second confirmatory value within a period of not more than 4 weeks; patients with a level greater than or equal to 100 U/mL may be entered without confirmatory measurement; the CA-125 assessment for eligibility must be done at least 4 weeks after paracentesis or other surgical procedures
•Detectable (non-measurable) disease is defined as symptomatic ascites or pleural effusions, solid and/or cystic abnormalities on radiographic imaging that do not meet Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 definitions for target lesions and/or biopsy proven recurrence
•Measurable disease will be defined by RECIST 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be \>= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or \>= 20 mm when measured by chest x-ray; lymph nodes must be \>= 15 mm in short axis when measured by CT or MRI
•Patients with measurable disease must have had at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy
•Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl
•This ANC cannot have been induced or supported by granulocyte colony-stimulating factors
•Platelets greater than or equal to 100,000/mcl

Exclusion Criteria

•Patients who have received more than one previous regimen of chemotherapy (maintenance is not considered a second regimen)
•Patients who have received prior ABT-888 or any other poly-adenosine diphosphate (ADP)--ribose polymerase (PARP) inhibitor
•Patients who have received prior PLD
•History of allergic reactions attributed to compounds of similar chemical or biologic composition to ABT-888 or other agents used in this study
•Patients with other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies are excluded if there is any evidence of other malignancy being present within the last three 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 (other than ovarian, fallopian tube and primary peritoneal) 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 synchronous primary endometrial cancer or a history of endometrial cancer, unless all of the following conditions are met:
•Stage not greater than IB
•No more than superficial myometrial invasion