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

NCT01017640 | Completed Phase 1 DMC

• 12 other identifiers: NCI-2012-01473OSU-09100OSU# 091002009C006909100NCI 8472CDR0000656393OSU 091008472N01CM00070N01CM62207P30CA016058
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I trial studies the side effects and best dose of veliparib when given with or without mitomycin C in treating patients with solid tumors that have spread to other places in the body, cannot be removed by surgery or have come back. 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, by stopping them from dividing, or by stopping them from spreading. Giving veliparib together with mitomycin C may kill more tumor cells.

Conditions

Solid Neoplasm

Outcome Measures

Primary Outcomes (5)

• Ability to safely deliver the combination of mitomycin C and veliparib

  Up to 12 weeks post-treatment

• Ability to safely deliver veliparib in a continuous dose as monotherapy

  Up to 12 weeks post-treatment

• Feasibility of screening for FA deficiency across different tumor types, defined as adequate number of patients deficient on this pathway

  Up to 12 weeks post-treatment

• Selection of a dose schedule of the combination of mitomycin C and veliparib for phase II trials

  Up to 12 weeks post-treatment

• Selection of a dose schedule of veliparib monotherapy for phase II trials

  Up to 12 weeks post-treatment

Secondary Outcomes (4)

• BRCA mutations

  Baseline

• FancD2 foci formation in peripheral blood mononuclear cells

  Up to week 5

• Foci produced by the histone variant gamma-H2AX

  Up to week 5

• Tumor shrinkage as assessed by radiological means

  Up to 12 weeks post-treatment

Study Arms (2)

Arm I (veliparib)

EXPERIMENTAL

Patients receive veliparib PO BID in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Drug: Veliparib

Arm II (veliparib and mitomycin C)

EXPERIMENTAL

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.

Other: Laboratory Biomarker Analysis; Drug: Mitomycin; Drug: Veliparib

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (veliparib); Arm II (veliparib and mitomycin C)

Mitomycin DRUG

Given IV

Also known as: Ametycine, MITO, MITO-C, Mito-Medac, Mitocin, Mitocin-C, Mitolem, MITOMYCIN C, Mitomycin-C, Mitomycin-X, Mitomycine C, Mitosol, Mitozytrex, Mutamycin, Mutamycine, NCI-C04706

Arm II (veliparib and mitomycin C)

Veliparib DRUG

Given PO

Also known as: ABT-888, PARP-1 inhibitor ABT-888

Arm I (veliparib); Arm II (veliparib and mitomycin C)

Eligibility Criteria

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

You may qualify if:

• 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
• Patients will be consented to have their existing, or about to be obtained, paraffin embedded tumor tissue screened for FA deficiency; screening will be performed on an ongoing basis on the breast, thoracic, gastrointestinal (GI), Georgetown University (GU), and gynecologic (GYN) Ohio State University (OSU) clinics, anteceding and concurrently with the clinical trial; it will continue until the numbers of patients required for the clinical trial are identified and enrolled; based on the estimation from our preliminary data of 15 to 30% of patients, depending on the primary organ site, having tumors deficient for the FA pathway we will need to screen around 300 patients' samples to identify 40-50 patients; none of the eligibility criteria defined above or below will need to be met for the screening portion, since FA deficient patients identified by screening may meet eligibility criteria for the clinical trial at a later time; (e.g., patient is undergoing standard of care treatment at the time of the screening); separate written consents for screening and for the clinical trial will be obtained from patients
• 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 (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 limits 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Georgetown Cancer Treatment Center

Georgetown, Kentucky, 40324, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Interventions

Mitomycin; Mitozytrex; veliparib

Intervention Hierarchy (Ancestors)

Mitomycins; Indolequinones; Quinones; Organic Chemicals; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Sameh Mikhail

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2009
• First Posted: November 20, 2009
• Study Start: October 1, 2009
• Primary Completion: May 1, 2016
• Last Updated: July 11, 2016

Record last verified: 2016-07

Locations

US (2)