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Testing Nivolumab as a Potential Targeted Treatment in Cancers With Mismatch Repair Deficiency (MATCH-Subprotocol Z1D)

Primary Purpose

Advanced Lymphoma, Advanced Malignant Solid Neoplasm, Hematopoietic and Lymphoid Cell Neoplasm

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Nivolumab
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Lymphoma focused on measuring Nivolumab, Lymphoma, Mismatch repair deficiency

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol
  • Patients must have mismatch repair deficiency as determined via the MATCH Master Protocol
  • Women of childbearing potential (WOCBP) receiving nivolumab must agree to use adequate contraception (hormonal or double barrier method of birth control; abstinence) from one week prior to study treatment starting, during treatment, and for a period of 5 months after the last dose of nivolumab. Men receiving nivolumab and who are sexually active with WOCBP must agree to use adequate contraception (hormonal or double barrier method of birth control; abstinence) from one week prior to study treatment starting, during treatment, and for a period of 7 months after the last dose of nivolumab

  • Patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection may be eligible provided they have the following:

    • There must be no evidence of clinically significant hepatic injury from hepatitis virus infection
    • For HBV, patients must be on suppressive therapy and have undetectable HBV viral load
    • For HCV, patients must either be on suppressive therapy for HCV or have already completed therapy thought to have eradicated HCV

Exclusion Criteria:

  • Patients must not have known hypersensitivity to nivolumab or compounds of similar chemical or biologic composition
  • No prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40 or anti-CTLA-4 antibodies (or any other antibody targeting T cell co-regulatory pathways)
  • Patients with cancers for which nivolumab is approved or becomes approved are excluded (e.g: colorectal cancer, locally advanced or metastatic urothelial carcinoma, unresectable or metastatic melanoma, metastatic non-small cell lung cancer, advanced renal cell carcinoma, classical Hodgkin lymphoma, and recurrent or metastatic squamous cancer of the head and neck)
  • Must not have received any of the following therapies within four weeks prior to the first dose of the study drug: IL-2, interferon, or other non-study immunotherapy regimens or immunosuppressive agents
  • Must not have a history of toxic epidermal necrolysis (Stevens-Johnson syndrome)
  • Must not have received growth factors, including but not limited to granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin, etc. within 2 weeks of study drug administration. Use of such agents while on study is also prohibited. Prior use of growth factors should be documented in the patient's medical history
  • Must not have a history of any autoimmune disease: inflammatory bowel disease, (including ulcerative colitis and Crohn's disease), rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus (SLE) autoimmune vasculitis (e.g., Wegener's Granulomatosis), central nervous system (CNS) or motor neuropathy considered to be of autoimmune origin (e.g., Guillain-Barre syndrome, myasthenia gravis, multiple sclerosis). Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event). Entry of patients with autoimmune diagnoses not listed here must be approved by the protocol chair
  • Must not be on supplemental home oxygen
  • Must not have evidence of interstitial lung disease
  • Patients with a requirement for steroid treatment or other immunosuppressive treatment: Patients will be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
  • No history of severe hypersensitivity reaction to any monoclonal antibody

Sites / Locations

  • ECOG-ACRIN Cancer Research Group

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (nivolumab)

Arm Description

Patients receive nivolumab IV over 30-60 minutes on days 1 and 15 of cycles 1-4 and on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Overall Response Rate (ORR)
Overall response rate was defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) among all eligible and treated patients. Best overall response was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. The 90% two-sided binomial exact confidence interval was calculated for ORR.

Secondary Outcome Measures

6-month Progression-free Survival (PFS) Rate
PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. The 6-month PFS rate was estimated using the Kaplan-Meier method which can provide a point estimate for any specific time point. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients.
Progression-free Survival (PFS)
PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients.

Full Information

First Posted
June 18, 2020
Last Updated
March 15, 2021
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT04439214
Brief Title
Testing Nivolumab as a Potential Targeted Treatment in Cancers With Mismatch Repair Deficiency (MATCH-Subprotocol Z1D)
Official Title
MATCH Treatment Subprotocol Z1D: Nivolumab in Patients With Tumors With Mismatch Repair Deficiency
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
May 31, 2016 (Actual)
Primary Completion Date
October 11, 2018 (Actual)
Study Completion Date
May 17, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II MATCH treatment trial identifies the effects of nivolumab in patients whose cancer has a genetic change called mismatch repair deficiency. Mismatch repair deficiency refers to cells that have mutations (changes) in certain genes that are involved in correcting mistakes made when DNA is copied in a cell. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells with mismatch repair deficiency to grow and spread. Researchers hope to learn if nivolumab will shrink this type of cancer or stop its growth.
Detailed Description
PRIMARY OBJECTIVE: I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma. SECONDARY OBJECTIVES: I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma. II. To evaluate time until death or disease progression. EXPLORATORY OBJECTIVES: I. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms. II. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens. OUTLINE: Patients receive nivolumab intravenously (IV) over 30-60 minutes on days 1 and 15 of cycles 1-4 and on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months if less than 2 years from study entry, and then every 6 months for year 3 from study entry. THE MATCH SCREENING TRIAL: Please see NCT02465060 for information on the MATCH Screening Protocol and applicable documents.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Lymphoma, Advanced Malignant Solid Neoplasm, Hematopoietic and Lymphoid Cell Neoplasm, Refractory Lymphoma, Refractory Malignant Solid Neoplasm, Refractory Plasma Cell Myeloma
Keywords
Nivolumab, Lymphoma, Mismatch repair deficiency

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
47 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (nivolumab)
Arm Type
Experimental
Arm Description
Patients receive nivolumab IV over 30-60 minutes on days 1 and 15 of cycles 1-4 and on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Biological
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
Overall response rate was defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) among all eligible and treated patients. Best overall response was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. The 90% two-sided binomial exact confidence interval was calculated for ORR.
Time Frame
assessed at baseline, then every 8 weeks for the first 2 years, then every 12 weeks in year 3, until disease progression
Secondary Outcome Measure Information:
Title
6-month Progression-free Survival (PFS) Rate
Description
PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. The 6-month PFS rate was estimated using the Kaplan-Meier method which can provide a point estimate for any specific time point. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients.
Time Frame
assessed at baseline, then every 8 weeks for the first 2 years, then every 12 weeks in year 3, until disease progression
Title
Progression-free Survival (PFS)
Description
PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients.
Time Frame
assessed at baseline, then every 8 weeks for the first 2 years, then every 12 weeks in year 3, until disease progression

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol Patients must have mismatch repair deficiency as determined via the MATCH Master Protocol Women of childbearing potential (WOCBP) receiving nivolumab must agree to use adequate contraception (hormonal or double barrier method of birth control; abstinence) from one week prior to study treatment starting, during treatment, and for a period of 5 months after the last dose of nivolumab. Men receiving nivolumab and who are sexually active with WOCBP must agree to use adequate contraception (hormonal or double barrier method of birth control; abstinence) from one week prior to study treatment starting, during treatment, and for a period of 7 months after the last dose of nivolumab Patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection may be eligible provided they have the following: There must be no evidence of clinically significant hepatic injury from hepatitis virus infection For HBV, patients must be on suppressive therapy and have undetectable HBV viral load For HCV, patients must either be on suppressive therapy for HCV or have already completed therapy thought to have eradicated HCV Exclusion Criteria: Patients must not have known hypersensitivity to nivolumab or compounds of similar chemical or biologic composition No prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40 or anti-CTLA-4 antibodies (or any other antibody targeting T cell co-regulatory pathways) Patients with cancers for which nivolumab is approved or becomes approved are excluded (e.g: colorectal cancer, locally advanced or metastatic urothelial carcinoma, unresectable or metastatic melanoma, metastatic non-small cell lung cancer, advanced renal cell carcinoma, classical Hodgkin lymphoma, and recurrent or metastatic squamous cancer of the head and neck) Must not have received any of the following therapies within four weeks prior to the first dose of the study drug: IL-2, interferon, or other non-study immunotherapy regimens or immunosuppressive agents Must not have a history of toxic epidermal necrolysis (Stevens-Johnson syndrome) Must not have received growth factors, including but not limited to granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin, etc. within 2 weeks of study drug administration. Use of such agents while on study is also prohibited. Prior use of growth factors should be documented in the patient's medical history Must not have a history of any autoimmune disease: inflammatory bowel disease, (including ulcerative colitis and Crohn's disease), rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus (SLE) autoimmune vasculitis (e.g., Wegener's Granulomatosis), central nervous system (CNS) or motor neuropathy considered to be of autoimmune origin (e.g., Guillain-Barre syndrome, myasthenia gravis, multiple sclerosis). Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event). Entry of patients with autoimmune diagnoses not listed here must be approved by the protocol chair Must not be on supplemental home oxygen Must not have evidence of interstitial lung disease Patients with a requirement for steroid treatment or other immunosuppressive treatment: Patients will be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease No history of severe hypersensitivity reaction to any monoclonal antibody
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nilofer S Azad
Organizational Affiliation
ECOG-ACRIN Cancer Research Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
ECOG-ACRIN Cancer Research Group
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19103
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
31765263
Citation
Azad NS, Gray RJ, Overman MJ, Schoenfeld JD, Mitchell EP, Zwiebel JA, Sharon E, Streicher H, Li S, McShane LM, Rubinstein L, Patton DR, Williams PM, Coffey B, Hamilton SR, Bahary N, Suga JM, Hatoum H, Abrams JS, Conley BA, Arteaga CL, Harris L, O'Dwyer PJ, Chen AP, Flaherty KT. Nivolumab Is Effective in Mismatch Repair-Deficient Noncolorectal Cancers: Results From Arm Z1D-A Subprotocol of the NCI-MATCH (EAY131) Study. J Clin Oncol. 2020 Jan 20;38(3):214-222. doi: 10.1200/JCO.19.00818. Epub 2019 Nov 25.
Results Reference
result

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Testing Nivolumab as a Potential Targeted Treatment in Cancers With Mismatch Repair Deficiency (MATCH-Subprotocol Z1D)

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