Testing the Addition of Immunotherapy Before Surgery for Patients With Sarcomatoid Mesothelioma
- Conditions
- Pleural Biphasic MesotheliomaPleural Sarcomatoid Mesothelioma
- Interventions
- Procedure: Surgical ProcedureProcedure: Computed TomographyProcedure: Magnetic Resonance ImagingProcedure: 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
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Sarcomatoid or sarcomatoid-dominant (> 50%) biphasic, pleural mesothelioma
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Stage: I-IIIA disease per Union for International Cancer Control (UICC) TNM Classification of Malignant Tumours 8th edition
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Measurable disease or non-measurable disease as defined
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No prior treatment which would be considered treatment for the primary neoplasm or impact the primary endpoint
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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.)
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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
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Age >= 18 years
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Eastern Cooperative Oncology Group (ECOG) performance status =< 2 or Karnofsky >= 60%
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Absolute neutrophil count (ANC) >= 1,000/mm^3
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Leukocytes >= 2,000/mm^3
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Platelet count >= 100,000/mm^3
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Creatinine =< 1.5 x upper limit of normal (ULN) OR creatinine clearance >= 40 mL/min
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Total bilirubin =<1.5 x ULN, except patients with Gilbert Syndrome who can have total bilirubin < 3.0 mg/dl
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Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 x ULN
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Alkaline (alk) phosphatase (phos) =< 3.0 x ULN
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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
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No active systemic infection requiring therapy, as well as positive tests for hepatitis B surface antigen or hepatitis C antibody
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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
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Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
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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
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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
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STEP 2 ELIGIBILITY CRITERIA: Completion of at least 1 cycle of treatment and not have an unresolved adverse event that would preclude surgery
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STEP 2 ELIGIBILITY CRITERIA: No evidence of progression that would preclude resection
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STEP 2 ELIGIBILITY CRITERIA: ECOG performance status =< 2 or Karnofsky >= 60%
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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%
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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
- 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
Group Intervention Description Treatment (nivolumab, ipilimumab, surgery) Surgical Procedure Patients 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) Nivolumab Patients 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) Ipilimumab Patients 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 Tomography Patients 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 Imaging Patients 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 Tomography Patients 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
Name Time Method Surgery Rate immediately 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
Name Time Method Major pathologic response Up 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 recurrence Time 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 events Up 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 rate Up to 5 years Will be determined per modified RECIST. Response rate will be reported with 95% exact confidence interval.
Trial Locations
- Locations (123)
Christiana Care Health System-Concord Health Center
🇺🇸Chadds Ford, Pennsylvania, United States
Providence Regional Cancer System-Aberdeen
🇺🇸Aberdeen, Washington, United States
Overlake Medical Center
🇺🇸Bellevue, Washington, United States
PeaceHealth Saint Joseph Medical Center
🇺🇸Bellingham, Washington, United States
Providence Regional Cancer System-Centralia
🇺🇸Centralia, Washington, United States
Swedish Cancer Institute-Edmonds
🇺🇸Edmonds, Washington, United States
Providence Regional Cancer Partnership
🇺🇸Everett, Washington, United States
Swedish Cancer Institute-Issaquah
🇺🇸Issaquah, Washington, United States
Kadlec Clinic Hematology and Oncology
🇺🇸Kennewick, Washington, United States
Providence Regional Cancer System-Lacey
🇺🇸Lacey, Washington, United States
PeaceHealth Saint John Medical Center
🇺🇸Longview, Washington, United States
Skagit Regional Health Cancer Care Center
🇺🇸Mount Vernon, Washington, United States
Valley Medical Center
🇺🇸Renton, Washington, United States
Swedish Medical Center-Ballard Campus
🇺🇸Seattle, Washington, United States
Swedish Medical Center-Cherry Hill
🇺🇸Seattle, Washington, United States
Swedish Medical Center-First Hill
🇺🇸Seattle, Washington, United States
PeaceHealth United General Medical Center
🇺🇸Sedro-Woolley, Washington, United States
Providence Regional Cancer System-Shelton
🇺🇸Shelton, Washington, United States
PeaceHealth Southwest Medical Center
🇺🇸Vancouver, Washington, United States
Providence Saint Mary Regional Cancer Center
🇺🇸Walla Walla, Washington, United States
North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
🇺🇸Yakima, Washington, United States
Providence Regional Cancer System-Yelm
🇺🇸Yelm, Washington, United States
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
PCR Oncology
🇺🇸Arroyo Grande, California, United States
Providence Saint Joseph Medical Center/Disney Family Cancer Center
🇺🇸Burbank, California, United States
Providence Queen of The Valley
🇺🇸Napa, California, United States
Providence Medical Foundation - Santa Rosa
🇺🇸Santa Rosa, California, United States
Providence Santa Rosa Memorial Hospital
🇺🇸Santa Rosa, California, United States
Beebe Medical Center
🇺🇸Lewes, Delaware, United States
Beebe South Coastal Health Campus
🇺🇸Millville, Delaware, United States
Delaware Clinical and Laboratory Physicians PA
🇺🇸Newark, Delaware, United States
Helen F Graham Cancer Center
🇺🇸Newark, Delaware, United States
Medical Oncology Hematology Consultants PA
🇺🇸Newark, Delaware, United States
Christiana Care Health System-Christiana Hospital
🇺🇸Newark, Delaware, United States
Beebe Health Campus
🇺🇸Rehoboth Beach, Delaware, United States
Christiana Care Health System-Wilmington Hospital
🇺🇸Wilmington, Delaware, United States
Mayo Clinic in Florida
🇺🇸Jacksonville, Florida, United States
Saint Luke's Cancer Institute - Boise
🇺🇸Boise, Idaho, United States
Saint Luke's Cancer Institute - Fruitland
🇺🇸Fruitland, Idaho, United States
Saint Luke's Cancer Institute - Meridian
🇺🇸Meridian, Idaho, United States
Saint Luke's Cancer Institute - Nampa
🇺🇸Nampa, Idaho, United States
Saint Luke's Cancer Institute - Twin Falls
🇺🇸Twin Falls, Idaho, United States
Rush - Copley Medical Center
🇺🇸Aurora, Illinois, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
Carle at The Riverfront
🇺🇸Danville, Illinois, United States
Northwestern Medicine Cancer Center Kishwaukee
🇺🇸DeKalb, Illinois, United States
Carle Physician Group-Effingham
🇺🇸Effingham, Illinois, United States
Northwestern Medicine Cancer Center Delnor
🇺🇸Geneva, Illinois, United States
Northwestern Medicine Glenview Outpatient Center
🇺🇸Glenview, Illinois, United States
Northwestern Medicine Grayslake Outpatient Center
🇺🇸Grayslake, Illinois, United States
Northwestern Medicine Lake Forest Hospital
🇺🇸Lake Forest, Illinois, United States
Carle Physician Group-Mattoon/Charleston
🇺🇸Mattoon, Illinois, United States
Northwestern Medicine Orland Park
🇺🇸Orland Park, Illinois, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Northwestern Medicine Cancer Center Warrenville
🇺🇸Warrenville, Illinois, United States
Rush-Copley Healthcare Center
🇺🇸Yorkville, Illinois, United States
Christiana Care - Union Hospital
🇺🇸Elkton, Maryland, United States
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, United States
Saint Patrick Hospital - Community Hospital
🇺🇸Missoula, Montana, United States
Carson Tahoe Regional Medical Center
🇺🇸Carson City, Nevada, United States
Cancer and Blood Specialists-Henderson
🇺🇸Henderson, Nevada, United States
Comprehensive Cancer Centers of Nevada - Henderson
🇺🇸Henderson, Nevada, United States
Comprehensive Cancer Centers of Nevada-Horizon Ridge
🇺🇸Henderson, Nevada, United States
Las Vegas Cancer Center-Henderson
🇺🇸Henderson, Nevada, United States
OptumCare Cancer Care at Seven Hills
🇺🇸Henderson, Nevada, United States
Comprehensive Cancer Centers of Nevada-Southeast Henderson
🇺🇸Henderson, Nevada, United States
GenesisCare USA - Henderson
🇺🇸Henderson, Nevada, United States
Las Vegas Urology - Green Valley
🇺🇸Henderson, Nevada, United States
Las Vegas Urology - Pebble
🇺🇸Henderson, Nevada, United States
Urology Specialists of Nevada - Green Valley
🇺🇸Henderson, Nevada, United States
Las Vegas Urology - Pecos
🇺🇸Las Vegas, Nevada, United States
OptumCare Cancer Care at Charleston
🇺🇸Las Vegas, Nevada, United States
University Medical Center of Southern Nevada
🇺🇸Las Vegas, Nevada, United States
Hope Cancer Care of Nevada
🇺🇸Las Vegas, Nevada, United States
Radiation Oncology Centers of Nevada Central
🇺🇸Las Vegas, Nevada, United States
Urology Specialists of Nevada - Central
🇺🇸Las Vegas, Nevada, United States
GenesisCare USA - Las Vegas
🇺🇸Las Vegas, Nevada, United States
Sunrise Hospital and Medical Center
🇺🇸Las Vegas, Nevada, United States
Las Vegas Prostate Cancer Center
🇺🇸Las Vegas, Nevada, United States
Las Vegas Urology - Sunset
🇺🇸Las Vegas, Nevada, United States
Urology Specialists of Nevada - Southwest
🇺🇸Las Vegas, Nevada, United States
Radiation Oncology Centers of Nevada Southeast
🇺🇸Las Vegas, Nevada, United States
Ann M Wierman MD LTD
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada - Northwest
🇺🇸Las Vegas, Nevada, United States
GenesisCare USA - Vegas Tenaya
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
GenesisCare USA - Fort Apache
🇺🇸Las Vegas, Nevada, United States
Las Vegas Urology - Cathedral Rock
🇺🇸Las Vegas, Nevada, United States
OptumCare Cancer Care at MountainView
🇺🇸Las Vegas, Nevada, United States
Las Vegas Urology - Smoke Ranch
🇺🇸Las Vegas, Nevada, United States
Urology Specialists of Nevada - Northwest
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada - Central Valley
🇺🇸Las Vegas, Nevada, United States
Hope Cancer Care of Nevada-Pahrump
🇺🇸Pahrump, Nevada, United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada - Town Center
🇺🇸Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada-Summerlin
🇺🇸Las Vegas, Nevada, United States
University Cancer Center
🇺🇸Las Vegas, Nevada, United States
Renown Regional Medical Center
🇺🇸Reno, Nevada, United States
Summerlin Hospital Medical Center
🇺🇸Las Vegas, Nevada, United States
Las Vegas Cancer Center-Medical Center
🇺🇸Las Vegas, Nevada, United States
OptumCare Cancer Care at Fort Apache
🇺🇸Las Vegas, Nevada, United States
Saint Mary's Regional Medical Center
🇺🇸Reno, Nevada, United States
Radiation Oncology Associates
🇺🇸Reno, Nevada, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Saint Charles Health System
🇺🇸Bend, Oregon, United States
Clackamas Radiation Oncology Center
🇺🇸Clackamas, Oregon, United States
Providence Cancer Institute Clackamas Clinic
🇺🇸Clackamas, Oregon, United States
Bay Area Hospital
🇺🇸Coos Bay, Oregon, United States
Providence Newberg Medical Center
🇺🇸Newberg, Oregon, United States
Providence Willamette Falls Medical Center
🇺🇸Oregon City, Oregon, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Providence Saint Vincent Medical Center
🇺🇸Portland, Oregon, United States
Saint Charles Health System-Redmond
🇺🇸Redmond, Oregon, United States