Phase 2 N=121 Randomized Treatment

Phase II ABT-888 With Cyclophosphamide

Ovarian Cancer · Primary Peritoneal Cancer · Serous Carcinoma Cancer · Triple-Negative Breast Cancer · Fallopian Tube Cancer

Bottom Line

View on ClinicalTrials.gov: NCT01306032 ↗

Enrolled (actual)

121

Serious AEs

4.3%

Results posted

May 2016

Primary outcome: Primary: Percentage of Participants With an Overall Response Rate — 9.5; 5.6; 0; 11.8 percentage of participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: ABT-888 (Drug); Cyclophosphamide (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: National Cancer Institute (NCI)
Primary completion: Dec 2014

Outcome Measures

Outcome	Result	p-value
PRIMARY Percentage of Participants With an Overall Response Rate	9.5; 5.6; 0; 11.8; 19.4; 3.4	—
PRIMARY Progression Free Survival	3; 2; 3; 3	0.034 sig
SECONDARY Number of Participants With Adverse Events	28; 24; 29; 14; 4; 6	—
SECONDARY Change in Poly-ADP Ribose (PAR) Concentration Levels From Baseline	-81; -88; -74; -85	—
SECONDARY Change in ϓH2AX- Positive Circulating Tumor Cells (CTCs) in Whole Blood	400; 200; 9.5	—
SECONDARY Number of Participants With Deleterious Mutations in DNA Repair Genes	28; 27	—

Summary

Background: - The experimental cancer treatment drug ABT-888 (Veliparib) works by preventing deoxyribonucleic acid (DNA) repair in tumor cells. Cyclophosphamide is a cancer treatment drug that works by causing DNA damage in cells, including cancer cells, resulting in cell death. However, because cyclophosphamide has strong and unpleasant side effects, researchers are interested in finding drugs that can be given in combination with cyclophosphamide that will allow a lower dose of cyclophosphamide to be given with similar effects. The combination of ABT-88 and cyclophosphamide may be an effective treatment for some types of cancer, such as certain kinds of breast or ovarian cancer and non-Hodgkin's lymphoma that often do not respond to standard therapies. Objectives: - To evaluate the safety and effectiveness of ABT-888 and cyclophosphamide in ovarian and breast cancer and in non-Hodgkin's lymphoma that have not responded to standard treatments. Eligibility: - Individuals at least 18 years of age who have been diagnosed with (1) (Breast cancer 1/2) BRCA1/2 ovarian cancer, primary peritoneal or ovarian high-grade carcinoma, or fallopian tube cancer; (2) triple-negative breast cancer (not responsive to hormone-related therapy); or (3) low grade non-Hodgkin's lymphoma. Design: * Participants will be screened with a full medical history and physical examination, blood and urine tests, and tumor imaging studies. Participants will be divided into two groups with different treatment subgroups. * Group 1: Participants who have BRCA-positive ovarian cancer, primary peritoneal or ovarian high-grade serous carcinoma, or fallopian tube cancer * Participants will receive either the combination of ABT-888 and cyclophosphamide, or cyclophosphamide alone. * Participants will take the study drug by mouth once a day for 21-day cycles of treatment, and will keep a diary to record drug doses and any side effects. * Participants will have clinic visits with blood and urine tests, imaging studies, and other examinations on days 1, 2, 7, and 14 of cycle 1, and on the first day of all other cycles. * Group 2: Participants who have triple-negative breast cancer or non-Hodgkin's lymphoma * Participants will receive either the combination of ABT-888 and cyclophosphamide, or cyclophosphamide alone. * Participants will take the study drug by mouth once a day for 21-day cycles of treatment, and will keep a diary to record drug doses and any side effects. * Participants will have clinic visits with blood and urine tests, imaging studies, and other examinations on days 1, 2, 7, and 14 of cycle 1, and on the first day of all other cycles. * Participants receiving only cyclophosphamide who show signs of disease progression after tumor imaging studies can receive the combination of ABT-888 with cyclophosphamide. * Treatment will continue as long as participants tolerate the drugs and the disease does not progress.

Eligibility Criteria

INCLUSION CRITERIA:
Patients with histologically documented:
BRCA-positive ovarian cancer (documented deleterious BRCA1/2 mutation or a BRCAPRO score of greater than or equal to 30%)
primary peritoneal or ovarian high-grade serous carcinoma or fallopian tube cancer (no requirement for BRCA status)
triple-negative breast cancer (documented estrogen receptor (ER) negative, progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (Her2/neu) negative from the original pathology report if considered adequate, or per The American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines (47, 48)) with metastasis to distant sites
Low-grade lymphoid malignancies (NHL), as described below, whose disease has progressed following at least one line of standard therapy:
Follicle center lymphoma, follicular or diffuse-recurrent/refractory
Marginal zone B-cell lymphoma: splenic, nodal, extranodal (this includes mucosa-associated lymphoid tissue (MALT)) - recurrent/refractory
Lymphoplasmacytic lymphoma - recurrent/refractory
Small lymphocytic lymphoma (SLL) (absolute lymphocytes count below 5,000)

Pathology must be confirmed by the registering institution. For patients who are eligible for the study due to a history of BRCA1/2 mutation, documented evidence of their mutation status must be provided prior to enrolling on the study.

Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as greater than or equal to 20 mm with conventional techniques or as greater than or equal to 10 mm with spiral computed tomography (CT) scan.
Any prior therapy or radiotherapy must have been completed greater than or equal to 4 weeks (greater than 6 weeks for nitrosoureas or mitomycin C) prior to enrollment on protocol, and the participant must have recovered to eligibility levels from prior toxicity. Patients must be greater than or equal to 2 weeks since any investigational agent administered as part of a Phase 0 study, and should have recovered to eligibility levels from any toxicities.
Patients who have had prior treatment with any PARP inhibitors are eligible unless the PARP inhibitor was administered in combination with cyclophosphamide.
Patients with bone metastases or hypercalcemia on bisphosphonate treatment are eligible to participate
Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of ABT-888 in patients less than 18 years of age, children are excluded from this study, but may be eligible for future pediatric Phase I combination trials.
Karnofsky performance status greater than or equal to 70%.
Life expectancy greater than 3 months.
Patients must have adequate organ and marrow function as defined below:
absolute neutrophil count greater than or equal to 1,500/microL (mcL)
platelets greater than or equal to 100,000/microL (mcL)
total bilirubin less than 1.5 times institutional upper limit of normal
Aspartate aminotransaminase (AST) serum glutamic oxaloacetic transaminase (SGOT)/alanine aminotransaminase (ALT) serum glutamic pyruvic transaminase (SGPT) less than or equal to 2.5 times institutional upper limit of normal
creatinine less than 1.5 times institutional upper limit of normal

--creatinine clearance greater than or equal to 60 mL/min for patients with creatinine

levels greater than or equal to 1.5 times institutional upper limit of normal.

The effects of ABT-888 on the developing human fetus are unknown. For this reason and because cyclophosphamide hydrochloride is known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (abstinence; female use of hormonal methods, or barrier methods of birth control; male use of a condom) prior to study entry, for the duration of study participation, and for 3 months after completion o

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Data sourced from ClinicalTrials.gov (NCT01306032). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.