A Study of Nivolumab and Chemotherapy Followed by Surgery for Mesothelioma

Feasibility and Safety of Neoadjuvant Nivolumab and Chemotherapy for Resectable Malignant Pleural Mesothelioma

This study will test whether giving nivolumab in combination with pemetrexed and either cisplatin or carboplatin before surgery is a safe and effective approach to treating resectable mesothelioma without delaying surgery.

Study Overview

• Status: Active, not recruiting
• Conditions: Malignant Pleural Mesothelioma
• Intervention / Treatment: Drug: Nivolumab; Drug: Pemetrexed; Drug: Cisplatin or Carboplatin

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Michael Offin, MD; Phone Number: 646-449-1778; Email: offinm@mskcc.org
• Study Contact Backup: Name: Marjorie Zauderer, MD; Phone Number: 646-608-3790

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Memoiral Sloan Kettering Basking Ridge
    • Middletown, New Jersey, United States, 07748
      • Memorial Sloan Kettering Monmouth
    • Montvale, New Jersey, United States, 07645
      • Memorial Sloan Kettering Bergen
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Commack
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering Westchester
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • Uniondale, New York, United States, 11553
      • Memorial Sloan Kettering Nassau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• Karnofsky performance status > 70%
• Pathologic diagnosis of malignant pleural mesothelioma.
• Potentially resectable by pleurectomy/decortication, as assessed by thoracic surgeon
• Negative serum pregnancy test in women of childbearing potential
• Female patients of childbearing potential must agree to use a highly effective form of contraception for the duration of the study and for at least 5 months after the last administration of nivolumab and at least 6 months after last administration of pemetrexed, whichever is longer
• Male patients with female partners of childbearing potential must agree to use a highly effective form of contraception for the duration of the study and for at least 7 months after the last administration of nivolumab and at least 3 months after the last administration of pemetrexed, whichever is longer
• Adequate archival or fresh tissue for correlative analysis. Archival tissue will be deemed acceptable as long as their was no interval therapy prior to cycle 1 day 1 of protocol therapy. If sufficient archival or fresh tissue is not available, then a repeat biopsy at baseline prior to starting study treatment will be required as long as medically safe and feasible
• Absolute neutrophil count ≥ 1000/mcL
• Total bilirubin ≤ 1.5 mg/dl
• AST and ALT ≤ 3.0 x upper limit of normal
• Creatinine ≤ 1.5 x upper limit of normal
• Negative HIV serology blood test

Exclusion Criteria:

• Prior treatment with chemotherapy or immunotherapy for mesothelioma
• Autoimmune disease requiring systemic immune modulating treatment during the past two years
• Pregnant or lactating women
• Known active hepatitis B or hepatitis C
• Current use of systemic prednisone at dose ≥ 10 mg daily (or the equivalent dose with another corticosteroid)
• Serious concurrent medical illness or another active cancer requiring treatment
• Active pneumonitis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: nivolumab with pemetrexed and cisplatin or carboplatin; Eligible patients will receive two cycles of neoadjuvant therapy with nivolumab 360 mg, pemetrexed 500 mg/m2, and cisplatin 75 mg/m2 or carboplatin AUC=5. Subsequently, they will undergo pleurectomy/decortication.	Drug: Nivolumab; nivolumab 360 mg; Drug: Pemetrexed; 500 mg/m^2; Drug: Cisplatin or Carboplatin; cisplatin 75 mg/m2 or carboplatin AUC=5

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of patients going to operating room for surgical resection	Patients who experience a greater than 30 day toxicity induced delay of surgery will be counted as a failure for the primary feasibility endpoint.	30 days of the initially planned date

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Bristol-Myers Squibb
• Investigators: Principal Investigator: Michael Offin, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2019
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): November 1, 2025

Study Registration Dates

• First Submitted: November 12, 2019
• First Submitted That Met QC Criteria: November 12, 2019
• First Posted (Actual): November 13, 2019

Study Record Updates

• Last Update Posted (Estimated): February 22, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Surgery; Nivolumab; Cisplatin; Carboplatin; Pemetrexed; 19-272
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Adenoma; Neoplasms, Mesothelial; Pleural Neoplasms; Mesothelioma; Mesothelioma, Malignant; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Folic Acid Antagonists; Carboplatin; Nivolumab; Pemetrexed
• Other Study ID Numbers: 19-272

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No