Pegylated Liposomal Doxorubicin Hydrochloride, Carboplatin, Veliparib, and Bevacizumab in Treating Patients With Recurrent Ovarian Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer

NCT01459380 | Completed Phase 1

• 5 other identifiers: NCI-2011-01977GOG-9927CDR0000713945U10CA180868U10CA027469
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 13

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.

Conditions

Ovarian 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

Outcome Measures

Primary Outcomes (3)

• DLT assessed by NCI CTCAE version 4

  16 weeks (first 4 courses)

• Dose-limiting toxicity (DLT), assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4

  28 days (first course)

• Incidence of adverse events as assessed by CTEP version 4 of the NCI CTCAE

  Toxicity will be tabulated.

  Up to 1 year

Secondary Outcomes (1)

• Objective tumor response (complete and partial response)

  Up to 1 year

Other Outcomes (4)

• Germline mutations, alterations and/or rearrangements in the BRCA1 or BRCA2 genes

  Baseline

• Immunohistochemical expression of BRCA1 and BRCA2

  Baseline

• Methylation status in the promoter of the BRCA1 or BRCA2 genes

  Baseline

Study Arms (2)

Regimen I (intermittent veliparib)

EXPERIMENTAL

Patients receive veliparib PO BID on days 1-7, and pegylated liposomal doxorubicin hydrochloride IV over 1 hour and carboplatin IV over 30 minutes on day 1.

Biological: Bevacizumab; Drug: Carboplatin; Other: Laboratory Biomarker Analysis; Drug: Pegylated Liposomal Doxorubicin Hydrochloride; Drug: Veliparib

Regimen II (continuous veliparib)

EXPERIMENTAL

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

Biological: Bevacizumab; Drug: Carboplatin; Other: Laboratory Biomarker Analysis; Drug: Pegylated Liposomal Doxorubicin Hydrochloride; Drug: Veliparib

Interventions

Bevacizumab BIOLOGICAL

Given IV

Also known as: Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar FKB238, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF

Regimen I (intermittent veliparib); Regimen II (continuous veliparib)

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Regimen I (intermittent veliparib); Regimen II (continuous veliparib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Regimen I (intermittent veliparib); Regimen II (continuous veliparib)

Pegylated Liposomal Doxorubicin Hydrochloride DRUG

Given IV

Also known as: ATI-0918, Caelyx, DOX-SL, Doxil, Doxilen, Doxorubicin HCl Liposome, Doxorubicin Hydrochloride Liposome, Duomeisu, Evacet, LipoDox, Liposomal Adriamycin, liposomal doxorubicin hydrochloride, Liposomal-Encapsulated Doxorubicin, Pegylated Doxorubicin HCl Liposome, S-Liposomal Doxorubicin, Stealth Liposomal Doxorubicin, TLC D-99

Regimen I (intermittent veliparib); Regimen II (continuous veliparib)

Veliparib DRUG

Given PO

Also known as: ABT-888, PARP-1 inhibitor ABT-888

Regimen I (intermittent veliparib); Regimen II (continuous veliparib)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Creatinine =\< 1.5 times institutional upper limit of normal (ULN)
• Bilirubin \< 1.2 times ULN
• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 3.0 times ULN
• Alkaline phosphatase =\< 2.5 times ULN
• Left ventricular ejection fraction (LVEF) greater than or equal to institutional lower limit of normal (LLN) as determined by gated cardiac radionucleotide scan (MUGA) or echocardiogram

You may not qualify if:

• 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
• 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 known chronic or active hepatitis or ongoing or active infection that requires parenteral antibiotics
• 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 of childbearing potential, not practicing adequate contraception, patients who are pregnant or patients who are breastfeeding are not eligible for this trial

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• NRG Oncology: collaborator

Study Sites (13)

University of Colorado Cancer Center - Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

Location

Augusta University Medical Center

Augusta, Georgia, 30912, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Hillcrest Hospital Cancer Center

Mayfield Heights, Ohio, 44124, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Women and Infants Hospital

Providence, Rhode Island, 02905, United States

Location

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Ovarian Neoplasms

Interventions

Bevacizumab; Immunoglobulin G; Disulfides; Carboplatin; liposomal doxorubicin; Doxorubicin; veliparib

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Coordination Complexes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Lisa Landrum

  NRG Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2011
• First Posted: October 25, 2011
• Study Start: October 11, 2011
• Primary Completion: June 8, 2016
• Study Completion: February 11, 2017
• Last Updated: July 22, 2019

Record last verified: 2019-07

Locations

US (13)