ABT-888 With or Without Mitomycin in Treating Patients With Metastatic, Unresectable, or Recurrent Solid Tumors - Full Text View

Sponsor:	Arthur G. James Cancer Hospital & Richard J. Solove Research Institute
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT01017640

Purpose

RATIONALE: ABT-888 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as mitomycin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving ABT-888 together with mitomycin may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of ABT-888 when given with or without mitomycin in treating patients with metastatic, unresectable, or recurrent solid tumors.

Condition	Intervention	Phase
Unspecified Adult Solid Tumor, Protocol Specific	Drug: mitomycin C Drug: veliparib	Phase I

Study Type:	Interventional
Study Design:	Masking: Open Label Primary Purpose: Treatment
Official Title:	ABT-888 as Monotherapy and in Combination With Mitomycin C in Patients With Solid Tumors With Deficiency in Homologous Recombination Repair

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Mitomycin ABT 888 Mitomycins

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

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 ]

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	75
Study Start Date:	October 2009
Estimated Primary Completion Date:	September 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Group I Patients receive oral ABT-888 twice daily in the absence of disease progression or unacceptable toxicity.	Drug: veliparib Given orally
Experimental: Group II Patients receive oral ABT-888 twice daily on days 1-7, 1-14, 1-21, or 1-28. 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.	Drug: mitomycin C Given IV Drug: veliparib Given orally

Detailed Description:

OBJECTIVES:

Primary

To screen cancer patients across different histological sites to identify those with functional defects in the Fanconi anemia (FA) pathway in their tumors.
To establish the safety and practicality of treating patients with FA-deficient tumors with the PARP inhibitor ABT-888 as protracted monotherapy.
To establish the safety and practicality of treating patients with FA-deficient tumors with the combination of mitomycin C and ABT-888.
To select a dose of ABT-888 protracted monotherapy and a dose-schedule of the combination of mitomycin C and ABT-888 for phase II trials in patients with FA-deficient tumors.

Secondary

To evaluate germ line FA-repair deficiency and BRCA mutations in peripheral blood mononuclear cell (PBMC) samples from patients treated with ABT-888.
To evaluate foci produced by the histone variant γH2AX in PBMC samples from patients treated with ABT-888 with or without mitomycin C in order to assess any possible effects of ABT-888 in the cellular sensing and processing of mitomycin C-induced DNA double-strand breaks.
To quantify the number of patients with antitumor responses.

OUTLINE: This is a dose-escalation study of ABT-888. Patients are assigned to 1 of 2 treatment groups.

Group I: Patients receive oral ABT-888 twice daily in the absence of disease progression or unacceptable toxicity.
Group II: Patients receive oral ABT-888 twice daily on days 1-7, 1-14, 1-21, or 1-28. 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.

Blood and tissue samples are collected periodically for further laboratory analysis, including BRCA mutation analysis and H2AX and FancD2 activation analysis.

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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed solid tumor malignancy for which no curative or standard therapy exists or for which standard therapy is no longer effective
- Metastatic, unresectable, or recurrent disease
Tumor demonstrates deficiency for the Fanconi anemia pathway, based on FATSI immunofluorescence screening
No known brain metastases (unless previously resected or irradiated and not clinically active)

PATIENT CHARACTERISTICS:

ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
Life expectancy > 3 months
Leukocytes ≥ 3,000/mcL
ANC ≥ 1,500/mcL
Hemoglobin ≥ 9 g/dL
Platelet count ≥ 100,000/mcL
Total bilirubin normal
AST/ALT ≤ 2.5 times upper limit of normal
Creatinine normal OR creatinine clearance ≥ 60 mL/min
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Able to swallow capsules
No history of allergic reactions attributed to compounds of similar chemical or biologic composition to ABT-888 or mitomycin C
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 limit compliance with study requirements
No recent seizure history

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No more than 2 prior chemotherapy regimens for metastatic disease
No prior PARP inhibitors, with the exception of patients enrolled on Group II who may have had prior treatment with ABT-888
Prior adjuvant/neoadjuvant chemotherapy, hormonal therapy, molecular target therapy, or Erb inhibitor therapy (e.g., erlotinib hydrochloride, Herceptin, sorafenib, or sunitinib) allowed
At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) or radiotherapy
- Prior mitomycin C allowed only for topical applications (bladder cancer) or chemoembolization (e.g., liver tumors)
At least 2 weeks since prior erlotinib hydrochloride, hormonal therapy, or limited-field palliative radiotherapy to bone, brain, or radiosurgery
No other concurrent investigational agents
No concurrent combination antiretroviral therapy for HIV-positive patients
No other concurrent anticancer agents or therapies

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01017640

Locations

United States, Ohio
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center	Recruiting
Columbus, Ohio, United States, 43210-1240
Contact: Ohio State University Cancer Clinical Trial Matching Service 866-627-7616 osu@emergingmed.com

Sponsors and Collaborators

Arthur G. James Cancer Hospital & Richard J. Solove Research Institute

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Miguel A. Villalona-Calero, MD

Arthur G. James Cancer Hospital & Richard J. Solove Research Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Miguel A. Villalona-Calero, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT01017640 History of Changes
Other Study ID Numbers:	CDR0000656393, OSU-09100
Study First Received:	November 19, 2009
Last Updated:	December 15, 2011
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:

Neoplasms
Mitomycins
Mitomycin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses

Pharmacologic Actions
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Alkylating Agents

ClinicalTrials.gov processed this record on February 09, 2012