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Testing the Addition of Immunotherapy Before Surgery for Patients With Sarcomatoid Mesothelioma

Phase 2
Recruiting
Conditions
Pleural Biphasic Mesothelioma
Pleural Sarcomatoid Mesothelioma
Interventions
Procedure: Surgical Procedure
Procedure: Computed Tomography
Procedure: Magnetic Resonance Imaging
Procedure: Positron Emission Tomography
Registration Number
NCT05647265
Lead Sponsor
Alliance for Clinical Trials in Oncology
Brief Summary

This phase II trial evaluates the safety and effectiveness of giving immunotherapy (nivolumab and ipilimumab) before surgery for controlling disease in patients with stage I-IIIa sarcomatoid mesothelioma. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving immunotherapy before surgery may be more effective at controlling disease in patients with sarcomatoid mesothelioma than giving immunotherapy alone.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the percentage of patients with potentially resectable non-epithelioid mesothelioma who are able to proceed with surgery after neoadjuvant ipilimumab and nivolumab.

II. To determine the progression-free survival rate at 12 months after the initiation of neoadjuvant ipilimumab and nivolumab.

SECONDARY OBJECTIVES:

I. To determine the rate of intra-operative or post-operative complications following neoadjuvant immunotherapy.

II. Best response per modified pleural Response Evaluation Criteria in Solid Tumors (RECIST).

III. Major pathologic response rate. IV. Time to recurrence after surgery.

EXPLORATORY OBJECTIVES:

I. To evaluate the association between the change in peripheral T cell clonality relative to baseline and treatment response.

II. To evaluate the association between PD-L1 expression at baseline and treatment response.

III. To evaluate whether a novel mesothelioma immune signature identified by Dr. Mansfield's laboratory is predictive of response.

OUTLINE:

Patients receive nivolumab intravenously (IV), ipilimumab IV, and may undergo surgery on study. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) and positron emission tomography (PET) throughout the trial.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
26
Inclusion Criteria
  • Sarcomatoid or sarcomatoid-dominant (> 50%) biphasic, pleural mesothelioma

  • Stage: I-IIIA disease per Union for International Cancer Control (UICC) TNM Classification of Malignant Tumours 8th edition

  • Measurable disease or non-measurable disease as defined

  • No prior treatment which would be considered treatment for the primary neoplasm or impact the primary endpoint

  • No treatment with hormones or other chemotherapeutic agents except for hormones administered for non-disease-related conditions (e.g., insulin for diabetes and or hormonal therapy for breast, prostate cancer etc.)

  • Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown

    * Therefore, for women of childbearing potential only, a negative pregnancy test done =< 14 days prior to registration is required

  • Age >= 18 years

  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 or Karnofsky >= 60%

  • Absolute neutrophil count (ANC) >= 1,000/mm^3

  • Leukocytes >= 2,000/mm^3

  • Platelet count >= 100,000/mm^3

  • Creatinine =< 1.5 x upper limit of normal (ULN) OR creatinine clearance >= 40 mL/min

  • Total bilirubin =<1.5 x ULN, except patients with Gilbert Syndrome who can have total bilirubin < 3.0 mg/dl

  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 x ULN

  • Alkaline (alk) phosphatase (phos) =< 3.0 x ULN

  • No active, known or suspected autoimmune disease except for 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

  • No active systemic infection requiring therapy, as well as positive tests for hepatitis B surface antigen or hepatitis C antibody

  • No history of any other condition that may require the initiation of anti-tumor necrosis factor alpha (TNFalpha) therapies or other immunosuppressant medications during the study

  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better

  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

  • STEP 2 ELIGIBILITY CRITERIA: Completion of at least 1 cycle of treatment and not have an unresolved adverse event that would preclude surgery

  • STEP 2 ELIGIBILITY CRITERIA: No evidence of progression that would preclude resection

  • STEP 2 ELIGIBILITY CRITERIA: ECOG performance status =< 2 or Karnofsky >= 60%

  • STEP 2 ELIGIBILITY CRITERIA: Predicted forced expiratory volume in 1 second (FEV1) > 35% and postoperative predicted diffusion capacity of the lung for carbon monoxide (DLCO) > 35%

  • STEP 2 ELIGIBILITY CRITERIA: Registration to step 2 no less than 21 days and no more than 90 days after the last dose of neoadjuvant therapy

Exclusion Criteria
  • No patients deemed to be unresectable or poor surgical candidates
  • No patients with chest wall invasion, peritoneal spread, contralateral pleural involvement, mediastinal organ involvement, vertebral involvement, or metastases to contralateral intrathoracic lymph nodes, or any supraclavicular nodes
  • No patients with a history of symptomatic interstitial lung disease

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Treatment (nivolumab, ipilimumab, surgery)Surgical ProcedurePatients receive nivolumab IV, ipilimumab IV, and may undergo surgery on study. Patients also undergo CT or MRI and PET throughout the trial.
Treatment (nivolumab, ipilimumab, surgery)NivolumabPatients receive nivolumab IV, ipilimumab IV, and may undergo surgery on study. Patients also undergo CT or MRI and PET throughout the trial.
Treatment (nivolumab, ipilimumab, surgery)IpilimumabPatients receive nivolumab IV, ipilimumab IV, and may undergo surgery on study. Patients also undergo CT or MRI and PET throughout the trial.
Treatment (nivolumab, ipilimumab, surgery)Computed TomographyPatients receive nivolumab IV, ipilimumab IV, and may undergo surgery on study. Patients also undergo CT or MRI and PET throughout the trial.
Treatment (nivolumab, ipilimumab, surgery)Magnetic Resonance ImagingPatients receive nivolumab IV, ipilimumab IV, and may undergo surgery on study. Patients also undergo CT or MRI and PET throughout the trial.
Treatment (nivolumab, ipilimumab, surgery)Positron Emission TomographyPatients receive nivolumab IV, ipilimumab IV, and may undergo surgery on study. Patients also undergo CT or MRI and PET throughout the trial.
Primary Outcome Measures
NameTimeMethod
Surgery Rateimmediately after the completion of neoadjuvant immunotherapy and surgery

The rate of surgery after neoadjuvant immunotherapy among the feasibility analysis population as well as the 80% and 95% exact Clopper-Pearson confidence intervals will be estimated.

Progression free survival (PFS)At 12 months after initiation of neoadjuvant immunotherapy

PFS will be determined per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The rate of PFS at 12 months after the initiation of neoadjuvant immunotherapy among the feasibility and efficacy analysis population as well as the 80% and 95% exact Clopper-Pearson confidence intervals will be estimated.

Secondary Outcome Measures
NameTimeMethod
Major pathologic responseUp to 5 years

Defined as =\< 10% residual viable tumor in the resected lung and lymph node tissue. Response rates will be reported with 95% exact confidence interval.

Time to recurrenceTime from surgery to disease relapse, progression, or second tumor, whichever occurs first, assessed up to 5 years

Time to recurrence will be estimated among those patients who receive surgery and will be characterized by estimating cumulative incidence function and conducting cause-specific and subdistribution hazard regression.

Incidence of adverse eventsUp to 5 years

The type of adverse events, the frequency of each type and its grade will be summarized. The frequency and the percentage of severe adverse events will be presented in bar charts over treatment phase (neoadjuvant immunotherapy, surgery) to describe the change of adverse event or complication severity over time. The rates of the pre-operative or post-operative complications (within 30 days of surgery) will be estimated with its exact 95% confidence interval.

Objective response rateUp to 5 years

Will be determined per modified RECIST. Response rate will be reported with 95% exact confidence interval.

Trial Locations

Locations (123)

Anchorage Associates in Radiation Medicine

🇺🇸

Anchorage, Alaska, United States

Anchorage Radiation Therapy Center

🇺🇸

Anchorage, Alaska, United States

Alaska Breast Care and Surgery LLC

🇺🇸

Anchorage, Alaska, United States

Alaska Oncology and Hematology LLC

🇺🇸

Anchorage, Alaska, United States

Alaska Women's Cancer Care

🇺🇸

Anchorage, Alaska, United States

Katmai Oncology Group

🇺🇸

Anchorage, Alaska, United States

Providence Alaska Medical Center

🇺🇸

Anchorage, Alaska, United States

Kingman Regional Medical Center

🇺🇸

Kingman, Arizona, United States

Mayo Clinic Hospital in Arizona

🇺🇸

Phoenix, Arizona, United States

Mayo Clinic in Arizona

🇺🇸

Scottsdale, Arizona, United States

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Anchorage Associates in Radiation Medicine
🇺🇸Anchorage, Alaska, United States
Site Public Contact
Contact
907-212-6871
AKPAMC.OncologyResearchSupport@providence.org
Alison K. Conlin
Principal Investigator

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