Clinical trial NCT05647265: Testing the Addition of Immunotherapy Before Surgery for Patients With Sarcomatoid Mesothelioma
Official title: Official Title Neoadjuvant Immunotherapy in Sarcomatoid Mesothelioma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Pleural Biphasic Mesothelioma
Pleural Sarcomatoid Mesothelioma
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2022-12-12
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Surgery Rate
timeFrame: immediately after the completion of neoadjuvant immunotherapy and surgery
measure: Progression free survival (PFS)
timeFrame: At 12 months after initiation of neoadjuvant immunotherapy
Secondary outcomes:
measure: Incidence of adverse events
timeFrame: Up to 5 years
measure: Objective response rate
timeFrame: Up to 5 years
measure: Major pathologic response
timeFrame: Up to 5 years
measure: Time to recurrence
timeFrame: Time from surgery to disease relapse, progression, or second tumor, whichever occurs first, assessed up to 5 years
Other outcomes:
measure: Biomarkers
timeFrame: Up to 5 years
Locations:
city: Anchorage
country: United States
facility: Anchorage Associates in Radiation Medicine
state: Alaska
city: Anchorage
country: United States
facility: Anchorage Radiation Therapy Center
state: Alaska
city: Anchorage
country: United States
facility: Alaska Breast Care and Surgery LLC
state: Alaska
city: Anchorage
country: United States
facility: Alaska Oncology and Hematology LLC
state: Alaska
city: Anchorage
country: United States
facility: Alaska Women's Cancer Care
state: Alaska
city: Anchorage
country: United States
facility: Katmai Oncology Group
state: Alaska
city: Anchorage
country: United States
facility: Providence Alaska Medical Center
state: Alaska
city: Kingman
country: United States
facility: Kingman Regional Medical Center
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic Hospital in Arizona
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
city: Arroyo Grande
country: United States
facility: PCR Oncology
state: California
city: Burbank
country: United States
facility: Providence Saint Joseph Medical Center/Disney Family Cancer Center
state: California
city: Napa
country: United States
facility: Providence Queen of The Valley
state: California
city: Santa Rosa
country: United States
facility: Providence Medical Foundation - Santa Rosa
state: California
city: Santa Rosa
country: United States
facility: Providence Santa Rosa Memorial Hospital
state: California
city: Lewes
country: United States
facility: Beebe Medical Center
state: Delaware
city: Millville
country: United States
facility: Beebe South Coastal Health Campus
state: Delaware
city: Newark
country: United States
facility: Delaware Clinical and Laboratory Physicians PA
state: Delaware
city: Newark
country: United States
facility: Helen F Graham Cancer Center
state: Delaware
city: Newark
country: United States
facility: Medical Oncology Hematology Consultants PA
state: Delaware
city: Newark
country: United States
facility: Christiana Care Health System-Christiana Hospital
state: Delaware
city: Rehoboth Beach
country: United States
facility: Beebe Health Campus
state: Delaware
city: Wilmington
country: United States
facility: Christiana Care Health System-Wilmington Hospital
state: Delaware
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Boise
country: United States
facility: Saint Luke's Cancer Institute - Boise
state: Idaho
city: Fruitland
country: United States
facility: Saint Luke's Cancer Institute - Fruitland
state: Idaho
city: Meridian
country: United States
facility: Saint Luke's Cancer Institute - Meridian
state: Idaho
city: Nampa
country: United States
facility: Saint Luke's Cancer Institute - Nampa
state: Idaho
city: Twin Falls
country: United States
facility: Saint Luke's Cancer Institute - Twin Falls
state: Idaho
city: Aurora
country: United States
facility: Rush - Copley Medical Center
state: Illinois
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Danville
country: United States
facility: Carle at The Riverfront
state: Illinois
city: DeKalb
country: United States
facility: Northwestern Medicine Cancer Center Kishwaukee
state: Illinois
city: Effingham
country: United States
facility: Carle Physician Group-Effingham
state: Illinois
city: Geneva
country: United States
facility: Northwestern Medicine Cancer Center Delnor
state: Illinois
city: Glenview
country: United States
facility: Northwestern Medicine Glenview Outpatient Center
state: Illinois
city: Grayslake
country: United States
facility: Northwestern Medicine Grayslake Outpatient Center
state: Illinois
city: Lake Forest
country: United States
facility: Northwestern Medicine Lake Forest Hospital
state: Illinois
city: Mattoon
country: United States
facility: Carle Physician Group-Mattoon/Charleston
state: Illinois
city: Orland Park
country: United States
facility: Northwestern Medicine Orland Park
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: Warrenville
country: United States
facility: Northwestern Medicine Cancer Center Warrenville
state: Illinois
city: Yorkville
country: United States
facility: Rush-Copley Healthcare Center
state: Illinois
city: Elkton
country: United States
facility: Christiana Care - Union Hospital
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
city: Missoula
country: United States
facility: Saint Patrick Hospital - Community Hospital
state: Montana
city: Carson City
country: United States
facility: Carson Tahoe Regional Medical Center
state: Nevada
city: Henderson
country: United States
facility: Cancer and Blood Specialists-Henderson
state: Nevada
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada - Henderson
state: Nevada
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada-Horizon Ridge
state: Nevada
city: Henderson
country: United States
facility: Las Vegas Cancer Center-Henderson
state: Nevada
city: Henderson
country: United States
facility: OptumCare Cancer Care at Seven Hills
state: Nevada
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada-Southeast Henderson
state: Nevada
city: Henderson
country: United States
facility: GenesisCare USA - Henderson
state: Nevada
city: Henderson
country: United States
facility: Las Vegas Urology - Green Valley
state: Nevada
city: Henderson
country: United States
facility: Las Vegas Urology - Pebble
state: Nevada
city: Henderson
country: United States
facility: Urology Specialists of Nevada - Green Valley
state: Nevada
city: Las Vegas
country: United States
facility: Las Vegas Urology - Pecos
state: Nevada
city: Las Vegas
country: United States
facility: OptumCare Cancer Care at Charleston
state: Nevada
city: Las Vegas
country: United States
facility: University Medical Center of Southern Nevada
state: Nevada
city: Las Vegas
country: United States
facility: Hope Cancer Care of Nevada
state: Nevada
city: Las Vegas
country: United States
facility: Radiation Oncology Centers of Nevada Central
state: Nevada
city: Las Vegas
country: United States
facility: Urology Specialists of Nevada - Central
state: Nevada
city: Las Vegas
country: United States
facility: GenesisCare USA - Las Vegas
state: Nevada
city: Las Vegas
country: United States
facility: Sunrise Hospital and Medical Center
state: Nevada
city: Las Vegas
country: United States
facility: Las Vegas Prostate Cancer Center
state: Nevada
city: Las Vegas
country: United States
facility: Las Vegas Urology - Sunset
state: Nevada
city: Las Vegas
country: United States
facility: Urology Specialists of Nevada - Southwest
state: Nevada
city: Las Vegas
country: United States
facility: Radiation Oncology Centers of Nevada Southeast
state: Nevada
city: Las Vegas
country: United States
facility: Ann M Wierman MD LTD
state: Nevada
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada - Northwest
state: Nevada
city: Las Vegas
country: United States
facility: GenesisCare USA - Vegas Tenaya
state: Nevada
city: Las Vegas
country: United States
facility: Las Vegas Urology - Cathedral Rock
state: Nevada
city: Las Vegas
country: United States
facility: Las Vegas Urology - Smoke Ranch
state: Nevada
city: Las Vegas
country: United States
facility: OptumCare Cancer Care at MountainView
state: Nevada
city: Las Vegas
country: United States
facility: Urology Specialists of Nevada - Northwest
state: Nevada
city: Las Vegas
country: United States
facility: Alliance for Childhood Diseases/Cure 4 the Kids Foundation
state: Nevada
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada - Town Center
state: Nevada
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada-Summerlin
state: Nevada
city: Las Vegas
country: United States
facility: Summerlin Hospital Medical Center
state: Nevada
city: Las Vegas
country: United States
facility: Las Vegas Cancer Center-Medical Center
state: Nevada
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Las Vegas
country: United States
facility: GenesisCare USA - Fort Apache
state: Nevada
city: Las Vegas
country: United States
facility: OptumCare Cancer Care at Fort Apache
state: Nevada
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada - Central Valley
state: Nevada
city: Las Vegas
country: United States
facility: University Cancer Center
state: Nevada
city: Pahrump
country: United States
facility: Hope Cancer Care of Nevada-Pahrump
state: Nevada
city: Reno
country: United States
facility: Renown Regional Medical Center
state: Nevada
city: Reno
country: United States
facility: Saint Mary's Regional Medical Center
state: Nevada
city: Reno
country: United States
facility: Radiation Oncology Associates
state: Nevada
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Bend
country: United States
facility: Saint Charles Health System
state: Oregon
city: Clackamas
country: United States
facility: Clackamas Radiation Oncology Center
state: Oregon
city: Clackamas
country: United States
facility: Providence Cancer Institute Clackamas Clinic
state: Oregon
city: Coos Bay
country: United States
facility: Bay Area Hospital
state: Oregon
city: Newberg
country: United States
facility: Providence Newberg Medical Center
state: Oregon
city: Oregon City
country: United States
facility: Providence Willamette Falls Medical Center
state: Oregon
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: Providence Saint Vincent Medical Center
state: Oregon
city: Redmond
country: United States
facility: Saint Charles Health System-Redmond
state: Oregon
city: Chadds Ford
country: United States
facility: Christiana Care Health System-Concord Health Center
state: Pennsylvania
city: Aberdeen
country: United States
facility: Providence Regional Cancer System-Aberdeen
state: Washington
city: Bellevue
country: United States
facility: Overlake Medical Center
state: Washington
city: Bellingham
country: United States
facility: PeaceHealth Saint Joseph Medical Center
state: Washington
city: Centralia
country: United States
facility: Providence Regional Cancer System-Centralia
state: Washington
city: Edmonds
country: United States
facility: Swedish Cancer Institute-Edmonds
state: Washington
city: Everett
country: United States
facility: Providence Regional Cancer Partnership
state: Washington
city: Issaquah
country: United States
facility: Swedish Cancer Institute-Issaquah
state: Washington
city: Kennewick
country: United States
facility: Kadlec Clinic Hematology and Oncology
state: Washington
city: Lacey
country: United States
facility: Providence Regional Cancer System-Lacey
state: Washington
city: Longview
country: United States
facility: PeaceHealth Saint John Medical Center
state: Washington
city: Mount Vernon
country: United States
facility: Skagit Regional Health Cancer Care Center
state: Washington
city: Renton
country: United States
facility: Valley Medical Center
state: Washington
city: Seattle
country: United States
facility: Swedish Medical Center-Ballard Campus
state: Washington
city: Seattle
country: United States
facility: Swedish Medical Center-Cherry Hill
state: Washington
city: Seattle
country: United States
facility: Swedish Medical Center-First Hill
state: Washington
city: Sedro-Woolley
country: United States
facility: PeaceHealth United General Medical Center
state: Washington
city: Shelton
country: United States
facility: Providence Regional Cancer System-Shelton
state: Washington
city: Vancouver
country: United States
facility: PeaceHealth Southwest Medical Center
state: Washington
city: Walla Walla
country: United States
facility: Providence Saint Mary Regional Cancer Center
state: Washington
city: Yakima
country: United States
facility: North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
state: Washington
city: Yelm
country: United States
facility: Providence Regional Cancer System-Yelm
state: Washington
Study officials:
References: