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.
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Inclusion Criteria:
- 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
- Patients must be able to swallow whole capsules and tolerate oral medications
- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and
for the duration of study participation; being not of childbearing potential is
defined as: (1) prior hysterectomy, or (2) no menstrual period for at least 24
months; should a woman become pregnant or suspect she is pregnant while participating
in this study, she should inform her treating physician immediately
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
- 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)