|Phase I Study of ABT-888 and Metronomic Cyclophosphamide in Patients With Refractory Solid Tumors or Lymphoma
First Published: 12/16/2008  Last Modified: 3/20/2012
Basic Trial Information
Trial Contact Information
ABT-888 and Cyclophosphamide in Treating Patients With Solid Tumors or Lymphoma That Did Not Respond to Previous Therapy
Basic Trial Information
|Phase I||Biomarker/Laboratory analysis, Treatment||Completed||18 and over||NCI-09-C-0048|
09-C-0048, 8275, P8437, NCT00810966
- Establish the safety and tolerability of ABT-888 when administered in combination with metronomic
cyclophosphamide in patients with refractory solid tumors or lymphoma.
- Establish the maximum tolerated dose of ABT-888 when administered in combination with metronomic
cyclophosphamide in these patients.
- Evaluate the pharmacokinetics of ABT-888 when administered in combination with
metronomic cyclophosphamide in these patients.
- Evaluate the antitumor response in these patients.
- Determine the effects of treatment on the level of PARP inhibition and γ-H2AX
in blood and tumor samples from these patients.
- Histologically confirmed solid tumor or lymphoid (e.g., lymphoma or chronic lymphocytic leukemia) malignancies
- Refractory to standard therapy or no acceptable
standard treatment options exists
- Patients with lymphoid malignancies must have disease progression after standard therapy AND have either refused stem cell transplantation (SCT) or SCT is not indicated
- No gliomas, symptomatic CNS metastases, or carcinomatous meningitis
- Patients with a history of CNS metastases are eligible, at the discretion of the principal investigator, provided they have received treatment and their CNS metastatic disease status has remained stable for ≥ 3 months without requiring steroids or anti-seizure medications
- See Disease Characteristics
- Recovered from prior therapy
- At least 4 weeks since prior chemotherapy (> 6 weeks for nitrosoureas or mitomycin C)
- At least 4 weeks since prior radiotherapy
- At least 2 weeks since prior investigational agents administered as part of a phase 0 study
- Prior ABT-888 as part of a single- or limited-dosing study (e.g., phase 0 study) allowed
- Prior cyclophosphamide allowed
- No concurrent protease inhibitors for HIV-positive patients
- No other concurrent chemotherapy
- No other concurrent investigational or commercial anticancer agents or therapies
- Karnofsky performance status 60-100%
- Life expectancy > 3 months
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Total bilirubin < 1.5 times upper limit of normal (ULN)
- AST and ALT ≤ 2.5 times ULN
- Creatinine < 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3 months after completion of study treatment
- No concurrent uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would preclude compliance with study requirements
- No history of seizures
- No gastrointestinal condition that may predispose patient to 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, or active peptic ulcer disease)
- No ulcerative colitis, inflammatory bowel disease, or partial or complete small bowel obstruction
Maximum tolerated dose of ABT-888 when administered in combination with metronomic
Pharmacokinetics of ABT-888
Level of PARP inhibition
Amount of γ-H2AX induction
This is a multicenter, dose-escalation study of ABT-888.
Patients receive oral ABT-888 once daily for 7-21 days and oral cyclophosphamide once daily for 14 or 21 days. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Plasma samples are collected periodically for pharmacodynamic and pharmacokinetic analysis. Samples are analyzed for PAR concentration by immunoassay, γ-H2AX levels by immunocytochemistry, quantification of the γ-H2AX marker and co-localization markers via quantitative immunofluorescence analysis, and ABT-888 concentration by liquid chromatography/mass spectrometry.
After completion of study therapy, patients are followed for 30 days.
Trial Contact Information
Trial Lead Organizations
NCI - Center for Cancer Research
|Shivaani Kummar, MD, Principal investigator|
|Official Title|| ||A Phase I Study of ABT-888 in Combination with Metronomic Cyclophosphamide in Adults with Refractory Solid Tumors and Lymphomas|
|Trial Start Date|| ||2008-12-10|
|Trial Completion Date|| ||2012-03-14|
|Registered in ClinicalTrials.gov|| ||NCT00810966|
|Date Submitted to PDQ|| ||2008-12-05|
|Information Last Verified|| ||2012-03-20|
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.