Nivolumab and Veliparib in Treating Patients With Recurrent or Refractory Stage IV Solid Tumors That Cannot Be Removed by Surgery or Lymphoma With or Without Alterations in DNA Repair Genes
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|ClinicalTrials.gov Identifier: NCT03061188|
Recruitment Status : Recruiting
First Posted : February 23, 2017
Last Update Posted : January 24, 2018
|Condition or disease||Intervention/treatment||Phase|
|Advanced Solid Neoplasm Aggressive Non-Hodgkin Lymphoma Recurrent Solid Neoplasm Refractory Mantle Cell Lymphoma T-Cell Non-Hodgkin Lymphoma Unresectable Solid Neoplasm||Other: Laboratory Biomarker Analysis Biological: Nivolumab Other: Pharmacological Study Drug: Veliparib||Phase 1|
I. To identify maximum tolerated dose (MTD) for the combination treatment of nivolumab and veliparib in patients with advanced refractory solid cancers and lymphoma.
I. To evaluate the safety and tolerability of nivolumab and veliparib in patients with advanced refractory solid cancers and lymphoma with and without mutations in selected DNA repair genes.
II. To evaluate the efficacy of treatment with nivolumab and veliparib in this population by objective response rate (ORR, defined as partial response [PR] + complete response [CR]), clinical benefit rate (CBR, defined as stable disease [SD] for >= 12 weeks, PR, + CR), and progression free survival (PFS, defined as the time from treatment initiation to documented disease progression) using Response Evaluation Criteria in Solid Tumors (RECIST) criteria version (v)1.1 or Lugano criteria.
III. To evaluate efficacy of treatment with nivolumab and veliparib in this population by ORR, CBR, and immune-related PFS (irPFS) using irRECIST criteria.
IV. To evaluate overall survival (OS) in this population at 3 years from the start of treatment.
V. To evaluate the proportion of patients alive and progression free at 24 weeks in this population.
VI. To evaluate ORR to nivolumab and veliparib in patients with prior exposure to single agent PD-1/PD-L1 inhibitors.
I. To evaluate if any of the following predict response to veliparib in combination with nivolumab: tissue PD-L1 protein expression, immune cell infiltration markers.
II. To demonstrate the pharmacodynamic effects of veliparib and nivolumab on biomarkers including PD-L1, TILs, T cell subpopulations, and T cell receptor genotype.
III. To explore the pattern of clonal changes through circulating cell free DNA assay.
IV. To assess the dynamic change in both immune and genomic biomarkers in blood that may correlate with response to veliparib.
OUTLINE: This is a dose-escalation study of veliparib.
Patients receive veliparib orally (PO) twice daily (BID) on day 1 and nivolumab intravenously (IV) over 30 minutes on days 1 and 15 of courses 1-4 and IV over 60 minutes on day 1 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 3, 6, 9, and 12 months and then every 6 months for 3 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/Ib Study of Nivolumab and Veliparib in Patients With Advanced Solid Tumors and Lymphoma With and Without Alterations in Selected DNA Repair Genes|
|Actual Study Start Date :||May 23, 2017|
|Estimated Primary Completion Date :||September 2020|
|Estimated Study Completion Date :||January 2021|
Experimental: Treatment (veliparib, nivolumab)
Patients receive veliparib PO BID on day 1 and nivolumab IV over 30 minutes on days 1 and 15 of courses 1-4 and IV over 60 minutes on day 1 of subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- Maximum Tolerated Dose (MTD) [ Time Frame: Up to 28 days ]The MTD will be defined as the highest dose that causes dose-limiting toxicities (DLTs) in <2 of 6 patients.
- Incidence of Adverse Events [ Time Frame: Up to 30 days after treatment discontinuation ]Evaluate the safety and tolerability of nivolumab and veliparib by assessing the number, frequency, and severity of adverse events as defined by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
- ORR [ Time Frame: Up to 30 days after the last dose of study treatment ]ORR (partial response (PR) + complete response (CR)) will be evaluated using RECIST criteria v1.1 or Lugano 2014 classification for assessment of Lymphoma and irRECIST.
- Clinical Benefit Rate (CBR) [ Time Frame: Up to 3 years ]CBR (defined as stable disease (SD) for ≥12 weeks, PR + CR) assessed by RECIST criteria v1.1 or Lugano 2014 classification for assessment of Lymphoma, and irRECIST
- Progression Free Survival (PFS) [ Time Frame: Up to 3 years ]PFS, defined as the time from treatment initiation to documented disease progression, evaluated by RECIST criteria v1.1 or Lugano 2014 classification for assessment of Lymphoma.
- immune-related PFS (irPFS) [ Time Frame: Up to 3 years ]irPFS assessed by irRECIST criteria.
- Overall Survival (OS) [ Time Frame: Up to 3 years ]OS is defined as the time from treatment initiation until death due to any cause, assessed up to 3 years.
- Proportion of patients alive and progression free [ Time Frame: At 24 weeks ]Evaluate the proportion of patients alive and progression free at 24 weeks.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03061188
|Contact: Study Coordinator||(312)email@example.com|
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|Contact: Young K. Chae, MD, MPH, MBA 312-695-0370|
|Principal Investigator: Young K. Chae, MD, MPH, MBA|
|Sub-Investigator: Benedito Carneiro, MD|
|Sub-Investigator: Sunandana Chandra, MD|
|Sub-Investigator: Jason Kaplan, MD|
|Sub-Investigator: Aparna Kalyan, MD|
|Sub-Investigator: Sarika Jain, MD|
|Sub-Investigator: Massimo Cristofanilli, MD|
|Sub-Investigator: Victoria Villaflor, MD|
|Sub-Investigator: Cesar Santa-Maria, MD|
|Sub-Investigator: Ricardo Costa, MD|
|Sub-Investigator: Valerie Nelson, MD|
|Sub-Investigator: Neal Christiansen, MD|
|Sub-Investigator: Alok Pant, MD|
|Sub-Investigator: Amanda Williams, PA|
|Sub-Investigator: Hannah Garret, APN|
|Sub-Investigator: Ellen Dammrich, APN|
|Sub-Investigator: Mark Agulnik, MD|
|Sub-Investigator: Frank Giles, MD|
|Principal Investigator:||Young K. Chae, MD, MPH, MBA||Northwestern University|