Cyclophosphamide and Veliparib in Treating Patients With Locally Advanced or Metastatic Breast Cancer

NCT01351909 | Active Not Recruiting Phase 1

• 8 other identifiers: NCI-2011-02590P8853_A18PAMDREVW0111-02-06811-01501CDR00007000338853N01CM62204P30CA013330
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 5

Brief Summary

This phase I trial studies the side effects and best dose of cyclophosphamide and veliparib when given together in treating patients with breast cancer that has spread from where it started to nearby tissue or lymph nodes or to other places in the body. Drugs used in chemotherapy, such as cyclophosphamide, 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. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving cyclophosphamide together with veliparib may work better in treating breast cancer.

Conditions

Locally Advanced Unresectable Breast Carcinoma; Stage IIIC Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IV Breast Cancer AJCC v6 and v7; Metastatic Breast Carcinoma; Recurrent Breast Carcinoma

Outcome Measures

Primary Outcomes (1)

• Recommended phase II dose of veliparib and cyclophosphamide

  The descriptions and grading scales found in the revised National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 will be utilized for adverse events reporting.

  21 days

Secondary Outcomes (4)

• Clinical response (complete or partial response) according to RECIST version 1.1

  Up to 24 weeks

• Overall survival

  Time from treatment initiation to death, assessed up to 6 years

• MacroH2A1.1 expression levels

  Up to 6 years

• PARP1 expression status

  Up to 6 years

Study Arms (1)

Treatment (veliparib, cyclophosphamide)

EXPERIMENTAL

Patients receive veliparib orally PO QD and cyclophosphamide PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Cyclophosphamide; Other: Laboratory Biomarker Analysis; Drug: Veliparib

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (veliparib, cyclophosphamide)

Cyclophosphamide DRUG

Given PO

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518, B-518, B518, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR 138719, WR- 138719, WR-138719, WR138719

Treatment (veliparib, cyclophosphamide)

Veliparib DRUG

Given PO

Also known as: ABT 888, ABT-888, ABT888, PARP-1 inhibitor ABT-888

Treatment (veliparib, cyclophosphamide)

Eligibility Criteria

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

You may qualify if:

• Phase I: Patients must have histologically confirmed breast cancer (metastatic breast cancer \[MBC\]) that is human epidermal growth factor receptor 2 (HER2/neu) negative (as determined by local pathology or reference laboratory), and have disease that is metastatic (stage IV \[TxNxM1\]) or locally advanced and not amenable to potentially curative surgical resection (eg, clinical stage IIIB-C)
• HER2/neu negative disease (performed on primary tumor and/or metastatic lesion using commercially available/approved assay in local institutional or reference laboratory), according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines
• National Comprehensive Cancer Network (NCCN) guidelines recommend for metastatic breast cancer "…biopsy documentation of first recurrence, if possible, and determination of hormone receptor status (estrogen receptor \[ER\] and progesterone receptor \[PR\]) and HER2 status…."; therefore, histologic and/or cytologic confirmation of metastatic disease is encouraged whenever feasible, but not required; in some circumstances, histologic confirmation may not be feasible (eg, bone metastases not amenable to biopsy and elevated cancer antigen \[CA\]27-29 tumor marker); for patients who have had histologic confirmation of metastatic disease, it is required that the biopsy confirm that the metastatic tumor is ER and/or PR positive, and HER2/neu negative; for patients in whom biopsy confirmation of metastatic disease is not feasible, it is required that the primary tumor be ER and/or PR-positive and HER2/neu negative
• Measurable disease (Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1) or non-measurable disease, with measurement obtained within 4 weeks of registration
• Phase I: Patients must have received at least one prior chemotherapy regimen for metastatic disease; patients with deleterious germ line mutations in breast cancer (BRCA)1 or BRCA2 are not required to have received prior chemotherapy for metastatic disease
• Patients must have had progressive disease after at least one line of endocrine therapy for metastatic disease (includes relapse while receiving endocrine therapy); there should be at least 1 week interval between the last endocrine treatment for an aromatase inhibitor and at least 2 weeks for tamoxifen or fulvestrant
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 (Karnofsky \>= 60%)
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Hemoglobin \>= 9 g/dl (per manufacturer recommendation)
• Total bilirubin within normal institutional limits (unless isolated indirect hyperbilirubinemia due to Gilbert's disease)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 × institutional upper limit of normal
• Creatinine within normal institutional limits OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
• Patients with a history of brain metastases are eligible if they have been treated with radiation and have stable brain metastases at least 3 months after radiation and must also be off steroids

You may not qualify if:

• Patients who have radiotherapy within 3 weeks prior to entering the study or those who have not recovered from adverse events due to systemic agents administered more than 3 weeks earlier
• Patients may not be receiving any other investigational agents
• Patients with known brain metastases with active symptoms or requiring anticonvulsive medications, or steroids should be excluded from this clinical trial
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to veliparib (ABT-888) or cyclophosphamide used in the study
• Evidence of complete or partial bowel obstruction or other unable to take oral medications
• Patients with malabsorption syndrome or other condition that would interfere with intestinal absorption
• Patients unable to swallow whole capsules
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant (positive pregnancy test) or lactating women will be excluded from the study; also, unwillingness to use effective means of contraception in subjects with child-bearing potential will be excluded from the study; women of child-bearing potential must use two forms of contraception (i.e., barrier contraception and one other method of contraception) at least 4 weeks prior to study entry, for the duration of study participation
• Patients with active severe infection; known infection with human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus, or severe concurrent illness will be excluded from the study; HIV-positive patients on combination antiretroviral therapy are ineligible
• Patients with a history of seizure disorder requiring antiepileptics who have had a seizure episode within the last 6 months
• Prior treatment with veliparib (ABT-888) or other PARP inhibitors (e.g., olaparib)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (5)

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

Location

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

Montefiore Medical Center-Einstein Campus

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center-Weiler Hospital

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center - Moses Campus

The Bronx, New York, 10467, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Cyclophosphamide; veliparib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Joseph A Sparano

  Montefiore Medical Center - Moses Campus

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2011
• First Posted: May 11, 2011
• Study Start: May 2, 2011
• Primary Completion: November 25, 2016
• Study Completion (Estimated): March 31, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-03

Locations

US (5)