Veliparib With or Without Mitomycin C in Treating Patients With Metastatic, Unresectable, or Recurrent Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01017640
First received: November 19, 2009
Last updated: July 16, 2014
Last verified: June 2014

November 19, 2009
July 16, 2014
October 2009
June 2015   (final data collection date for primary outcome measure)
  • Feasibility of screening for FA deficiency across different tumor types, defined as adequate number of patients deficient on this pathway [ Time Frame: Up to 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • Ability to safely deliver veliparib in a continuous dose as monotherapy [ Time Frame: Up to 12 weeks post-treatment ] [ Designated as safety issue: Yes ]
  • Ability to safely deliver the combination of mitomycin C and veliparib [ Time Frame: Up to 12 weeks post-treatment ] [ Designated as safety issue: Yes ]
  • Selection of a dose schedule of veliparib monotherapy for phase II trials [ Time Frame: Up to 12 weeks post-treatment ] [ Designated as safety issue: Yes ]
  • Selection of a dose schedule of the combination of mitomycin C and veliparib for phase II trials [ Time Frame: Up to 12 weeks post-treatment ] [ Designated as safety issue: Yes ]
  • Feasibility of screening for Fanconi anemia (FA) deficiency across different tumor types, and that patients deficient in this pathway (no FancD2 foci formation in their tumors) exist in adequate number to justify further trials [ Designated as safety issue: No ]
  • Ability to safely deliver ABT-888 in a continuous dose as monotherapy [ Designated as safety issue: Yes ]
  • Ability to safely deliver the combination of mitomycin C and ABT-888 [ Designated as safety issue: Yes ]
  • Selection of a dose schedule of ABT-888 monotherapy and the combination of mitomycin C and ABT-888 for phase II trials [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01017640 on ClinicalTrials.gov Archive Site
  • FancD2 foci formation in peripheral blood mononuclear cells [ Time Frame: Up to week 5 ] [ Designated as safety issue: No ]
    Descriptive statistics will be provided: proportions for categorical variables; mean and standard deviation for the continuous variables.
  • BRCA mutations [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Descriptive statistics will be provided: proportions for categorical variables; mean and standard deviation for the continuous variables.
  • Foci produced by the histone variant gamma-H2AX [ Time Frame: Up to week 5 ] [ Designated as safety issue: No ]
    Descriptive statistics will be provided: proportions for categorical variables; mean and standard deviation for the continuous variables.
  • Tumor shrinkage as assessed by radiological means [ Time Frame: Up to 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • FancD2 foci formation in peripheral blood mononuclear cells [ Designated as safety issue: No ]
  • BRCA mutations [ Designated as safety issue: No ]
  • Foci produced by the histone variant γH2AX [ Designated as safety issue: No ]
  • Tumor shrinkage as assessed by radiology [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Veliparib With or Without Mitomycin C in Treating Patients With Metastatic, Unresectable, or Recurrent Solid Tumors
ABT-888 as Monotherapy and in Combination With Mitomycin C in Patients With Solid Tumors With Deficiency in Homologous Recombination Repair

This phase I trial studies the side effects and best dose of veliparib when given with or without mitomycin C in treating patients with metastatic, unresectable, or recurrent solid tumors. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as mitomycin C, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving veliparib together with mitomycin C may kill more tumor cells.

PRIMARY OBJECTIVES:

I. To screen cancer patients across different histological sites to identify those with functional defects in the Fanconi anemia (FA) pathway in their tumors.

II. To establish the safety and practicality of treating patients with FA-deficient tumors with the poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor ABT-888 (veliparib) as protracted monotherapy.

III. To establish the safety and practicality of treating patients with FA-deficient tumors with the combination of mitomycin C (MMC) and ABT-888.

IV. To select a dose of ABT-888 protracted monotherapy and a dose-schedule of the combination of mitomycin C and ABT-888 in patients with FA deficient tumors for phase 2 trials.

SECONDARY OBJECTIVES:

I. To evaluate for germ-line FA repair deficiency and BRCA mutations in peripheral blood mononuclear (PBMC) in patients receiving ABT-888 treatment.

II. To evaluate in PBMC samples for foci produced by the histone variant gamma-H2A histone family, member X (H2AX) in patients receiving mitomycin C with or without ABT-888 in order to assess any possible effect of ABT-888 in the cellular sensing and processing of mitomycin C-induced deoxyribonucleic acid (DNA) double strand breaks.

III. Quantify the number of patients with antitumor responses.

OUTLINE: This is a dose-escalation study of veliparib. Patients are assigned to 1 of 2 treatment arms.

ARM I: Patients receive veliparib orally (PO) twice daily (BID) in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive veliparib PO BID on days 1-7, 1-14, or 1-21. Patients also receive mitomycin C intravenously (IV) over 10-20 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 12 weeks.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Unspecified Adult Solid Tumor, Protocol Specific
  • Drug: veliparib
    Given PO
    Other Name: ABT-888
  • Drug: mitomycin C
    Given IV
    Other Names:
    • MITC
    • MITO
    • MITO-C
    • Mitocin-C
    • MTC
  • Other: laboratory biomarker analysis
    Correlative studies
  • Experimental: Arm I (veliparib)
    Patients receive veliparib PO BID in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: veliparib
    • Other: laboratory biomarker analysis
  • Experimental: Arm II (veliparib and mitomycin C)
    Patients receive veliparib PO BID on days 1-7, 1-14, or 1-21. Patients also receive mitomycin C IV over 10-20 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: veliparib
    • Drug: mitomycin C
    • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
75
Not Provided
June 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients must have a histologically confirmed solid malignancy that is metastatic, or unresectable, or recurrent, for which no curative or standard of care exist, or this standard of care is no longer effective
  • Tumors have been shown to be deficient for the FA pathway, based on Fanconi anemia triple stain immunofluorescence (FATSI) screening
  • Up to two chemotherapy regimens for metastatic disease are allowed; in addition, prior adjuvant/neo-adjuvant chemotherapy, hormonal therapy, molecular targeted therapy or estrogen receptor B (Erb) inhibitor treatments (e.g., erlotinib, Herceptin, sorafenib, sunitinib) will be allowed and will not count towards eligibility; at least 4 weeks must elapse since prior chemotherapy or radiation therapy (two weeks for erlotinib, hormonal therapy, or limited field palliative radiation to bone, brain, or radiosurgery), 6 weeks if the last regimen included nitrosoureas or mitomycin C; previous use of mitomycin C would be restricted to topical applications (bladder cancer) or chemoembolization (e.g., liver tumors)
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 OR Karnofsky >= 60%
  • Life expectancy of greater than 3 months
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count (ANC) >= 1,500/mcL
  • Hemoglobin >= 9 g/dL
  • Platelets >= 100,000/mcL
  • Total bilirubin within normal institutional limit
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
  • Creatinine within normal institutional limit OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • 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; 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
  • Patients should be able to swallow capsules
  • EXPANSION COHORT:

    • Diagnosis of colorectal malignancy
    • Absence of Fanconi anemia, complementation group D2 (FANCD2) foci by FATSI screening
    • Presence of biopsiable lesion by imaging
    • Consent to a baseline (prior to treatment) tumor biopsy and for a repeat biopsy at the time of progression on the event that an antitumor response is demonstrated on the MMC-ABT-888 regimen
    • Same eligibility as above, except that they will have no limitations related prior number of chemotherapy regimens given; patients could have received prior treatment with PARP inhibitors if used as single agent

Exclusion Criteria:

  • Patients may not be receiving any other investigational agents
  • Patients with known central nervous system (CNS) metastases (unless previously resected or irradiated and not clinically active); patients with CNS metastases must be stable after therapy for > 3 months and off steroid treatment prior to study enrollment
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition as ABT-888 or Mitomycin C
  • 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 women are excluded from this study; breastfeeding should be discontinued
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
  • Patients with active seizure or a history of seizures
  • Patients previously treated with PARP inhibitors; with the exception of patients enrolled on Arm 2 who may have had prior treatment with PARP inhibitors as monotherapy
Both
18 Years and older
No
United States
 
NCT01017640
NCI-2012-01473, NCI-2012-01473, OSU-09100, CDR0000656393, OSU 09100, 8472, N01CM00070, N01CM62207, P30CA016058
Yes
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Miguel Villalona-Calero Ohio State University
National Cancer Institute (NCI)
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP