ABT-888 Plus Metronomic Cyclophosphamide to Treat Cancer

NCT01445522 | Completed Phase 1

• 2 other identifiers: 09004809-C-0048
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

Brief Summary

Background:

• Cyclophosphamide (CP) is a drug approved by the Food and Drug Administration for the treatment of certain cancers. It works by causing DNA damage, resulting in cell death, including cancer cells.
• ABT-888 is an experimental drug that has been given to a small number of patients. It works by preventing DNA repair in tumor cells. Objectives:
• To test the safety of the combination of ABT-888 and CP, and to determine the dose of each drug that can be given together to patients with cancer.
• To see how the body handles ABT-888 when given together with CP
• To evaluate the anti-tumor response of the drug combination. Eligibility:
• Adults with solid tumors or lymphoid cancers (lymphoma and chronic lymphocytic leukemia) whose disease does not respond to standard treatments. Design:
• Patients take ABT-888 by mouth once a day for 7, 14 or 21 days, depending on the dose level assigned to the individual patient.
• Patients take CP by mouth once a day every day in 21-day cycles. (Some patients take CP for 14 days only.)
• Patients undergo tests and procedures periodically during the study, including:
• Clinic visit and physical examination at the beginning of each cycle
• Blood and urine tests, electrocardiogram, measurement of vital signs
• CT scans, MRI scans or ultrasound tests to check the response of the tumor to treatment
• Tumor biopsies (optional)
• Bone marrow aspiration and biopsy

Conditions

Neoplasms; Lymphoma

Keywords

PARP Inhibitor; DNA Damage; Chemotherapy; Advanced Cancer; DNA Repair

Outcome Measures

Primary Outcomes (1)

• Establish the safety and tolerability of the combination of ABT-888 with metronomic cyclophosphamide in patients with refractory solid tumors and lymphomas. Establish the MTD of the combination of ABT-888 with metronomic cyclophosphamide.

Secondary Outcomes (1)

• Evaluate the pharmacokinetics of ABT-888 when administered combination with cyclophosphamide. Evaluate for anti-tumor response.

Interventions

ABT-888 DRUG

Cyclophosphamide DRUG

Eligibility Criteria

• Age: 18 Years - 110 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically documented solid tumors or lymphoid malignancies (lymphoma and CLL) refractory to standard therapy or who have no acceptable standard treatment options. Patients with lymphoid malignancies will be eligible if their disease has progressed following standard therapy and if stem cell transplantation is not indicated or has been refused.
• Any prior therapy 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 (CTCAE Grade less than or equal to 1) from prior toxicity. Prior radiation should have been completed greater than or equal to 4 weeks prior to study enrollment, and all associated toxicities should have resolved to eligibility levels. 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.
• 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 60%, see Appendix A.
• Life expectancy of greater than 3 months.
• Patients must have normal 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 the institutional upper limit of normal
• AST(SGOT)/ALT(SGPT) less than or equal to 2.5 times the institutional upper limit of normal
• creatinine less than 1.5 times the institutional upper limit of normal
• creatinine clearance greater than or equal to 60 mL/min for patients with creatinine levels 1.5 times the institutional upper limit of normal.
• The effects of ABT-888 on the developing human fetus are unknown. For this reason and because cyclophosphamide hydrochloride used in this trial 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 of study. Because there is a risk for adverse events in nursing infants secondary to treatment of the mother with cyclophosphamide, breastfeeding should be discontinued while the patient is on this trial and for 30 days after completion of treatment on this trial. 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.

You may not qualify if:

• \- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. 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 been administered ABT-888 as part of a single or limited dosing study, such as a Phase 0 study, should not be excluded from participating in this study solely because of receiving prior ABT-888.
• Patients who have received prior cyclophosphamide should not be excluded solely because of receiving prior cyclophosphamide.
• 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.
• Patients with gliomas, symptomatic CNS metastases or carcinomatous meningitis are excluded from this clinical trial. Patients with history of CNS metastases who have received treatment and whose CNS metastatic disease status has remained stable for greater than or equal to 3 months without steroids or anti-seizure medications may be eligible. These patients may be enrolled at the discretion of the principal investigator.
• Patients with a history of seizures.
• Patients with HIV who are taking protease inhibitors.
• Patients with gastrointestinal conditions that might predispose for drug intolerability or poor drug absorption (e.g., inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, malabsorption syndrome, active peptic ulcer disease) are excluded. Subjects with ulcerative colitis, inflammatory bowel disease, or a partial or complete small bowel obstruction are also excluded.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Alderson T. New targets for cancer chemotherapy--poly(ADP-ribosylation) processing and polyisoprene metabolism. Biol Rev Camb Philos Soc. 1990 Nov;65(4):623-41. doi: 10.1111/j.1469-185x.1990.tb01240.x. No abstract available.

  PMID: 2124932 BACKGROUND

• Ame JC, Rolli V, Schreiber V, Niedergang C, Apiou F, Decker P, Muller S, Hoger T, Menissier-de Murcia J, de Murcia G. PARP-2, A novel mammalian DNA damage-dependent poly(ADP-ribose) polymerase. J Biol Chem. 1999 Jun 18;274(25):17860-8. doi: 10.1074/jbc.274.25.17860.

  PMID: 10364231 BACKGROUND

• Ame JC, Spenlehauer C, de Murcia G. The PARP superfamily. Bioessays. 2004 Aug;26(8):882-93. doi: 10.1002/bies.20085.

  PMID: 15273990 BACKGROUND

MeSH Terms

Conditions

Neoplasms; Lymphoma

Interventions

veliparib; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Shivaani Kummar, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH

Study Record Dates

• First Submitted: September 30, 2011
• First Posted: October 3, 2011
• Study Start: December 3, 2008
• Primary Completion: July 3, 2012
• Study Completion: July 3, 2012
• Last Updated: December 17, 2019

Record last verified: 2012-06-29

Locations

US (2)