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Response to PARP Inhibitor Predicted by the RAD51 Assay

NCT03044795 · Status: WITHDRAWN · Phase: PHASE2 · Type: INTERVENTIONAL

Last updated 2024-05-03

No results posted yet for this study

Summary

In tumors with a defect in the homologous recombination (HR) pathway, double-strand break repair is partly impaired. Patients with HR deficient tumors benefit from therapies that induce DNA lesions requiring HR for repair. These therapies include platinum compounds and inhibitors of the enzyme PARP-1. At this moment, selection for PARP inhibitor treatment relies on detection of germ-line or somatic mutations in the HR pathway genes BRCA1 or BRCA2. However, not all HR deficient tumors have a BRCA gene mutation, the BRCA genes can also be silenced by promoter methylation. Moreover, the HR pathway can be defective due to mutations in other HR genes. In addition, the presence of a BRCA gene mutation does not guarantee defective HR since mutations in other genes (e.g. TP53BP1) can restore HR despite the presence of a BRCA1 mutation. Since all patients with tumors that are HR deficient may benefit from PARP inhibition, better tools are required to identify these patients. Recently, a functional ex vivo test for HR deficiency (the RAD51 assay) became available for clinical use. The RAD51 assay can identify patients with functional defects in HR-repair and may predict which cancer patients are likely to benefit from PARP inhibition. The purpose of this study is to investigate whether the RAD51 assay can select patients who will benefit from treatment with the PARP-inhibitor veliparib.

Conditions

Interventions

DRUG

Veliparib

Subjects in part A and part B will all start treatment with oral veliparib monotherapy twice a day. Patients will receive oral veliparib BID on days 1- 21, q3 weeks. All subjects will start with veliparib 300 mg, if the subject tolerates 300 mg BID for 2 weeks, veliparib may be increased to 400 mg BID at the investigator's discretion. Subjects will self-administer the morning dose and the evening dose of veliparib approximately 12 hours after the morning dose with or without food. ANC must be above 1.5 × 109/L in order to commence a new cycle.

Sponsors & Collaborators

  • AbbVie

    collaborator INDUSTRY

  • Dutch Cancer Society

    collaborator OTHER

  • University Medical Center Groningen

    lead OTHER

Principal Investigators

  • J. A. Gietema, MD, PhD · University Medical Center Groningen

Study Design

Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2019-11-30
Primary Completion
2020-11-30
Completion
2020-11-30

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03044795 on ClinicalTrials.gov