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

Pleural Biphasic Mesothelioma Clinical Trial

Official title:

Official Title Neoadjuvant Immunotherapy in Sarcomatoid Mesothelioma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05647265
• Other study ID #: A082101
• Secondary ID: NCI-2022-09320U1
• Status: Recruiting
• Phase: Phase 2
• Start date: March 14, 2023
• Est. completion date: December 15, 2024

Study information

• Verified date: May 2024
• Source: Alliance for Clinical Trials in Oncology
• Contact: Aaron Mansfield, MD
• Phone: 507-293-0569
• Email: mansfield.aaron[@]mayo.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 26
• Est. completion date: December 15, 2024
• Est. primary completion date: December 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Mesothelioma
• Mesothelioma, Malignant
• Pleural Biphasic Mesothelioma
• Pleural Sarcomatoid Mesothelioma

Intervention

Biological:
• Nivolumab
Given IV
• Ipilimumab
Given IV

Procedure:
• Surgical Procedure
Undergo surgery
• Computed Tomography
undergo CT
• Magnetic Resonance Imaging
Undergo MRI
• Positron Emission Tomography
Undergo PET

Locations

Country	Name	City	State
United States	PCR Oncology	Arroyo Grande	California
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	Overlake Medical Center	Bellevue	Washington
United States	Carson Tahoe Regional Medical Center	Carson City	Nevada
United States	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania
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	Duke University Medical Center	Durham	North Carolina
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Christiana Care - Union Hospital	Elkton	Maryland
United States	Beebe South Coastal Health Campus	Frankford	Delaware
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	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	Comprehensive Cancer Centers of Nevada-Southeast Henderson	Henderson	Nevada
United States	GenesisCare USA - Henderson	Henderson	Nevada
United States	Las Vegas Cancer Center-Henderson	Henderson	Nevada
United States	Las Vegas Urology - Green Valley	Henderson	Nevada
United States	Las Vegas Urology - Pebble	Henderson	Nevada
United States	OptumCare Cancer Care at Seven Hills	Henderson	Nevada
United States	Urology Specialists of Nevada - Green Valley	Henderson	Nevada
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Kingman Regional Medical Center	Kingman	Arizona
United States	Northwestern Medicine Lake Forest Hospital	Lake Forest	Illinois
United States	Alliance for Childhood Diseases/Cure 4 the Kids Foundation	Las Vegas	Nevada
United States	Ann M Wierman MD LTD	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Northwest	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	GenesisCare USA - Fort Apache	Las Vegas	Nevada
United States	GenesisCare USA - Las Vegas	Las Vegas	Nevada
United States	GenesisCare USA - Vegas Tenaya	Las Vegas	Nevada
United States	Hope Cancer Care of Nevada	Las Vegas	Nevada
United States	Las Vegas Cancer Center-Medical Center	Las Vegas	Nevada
United States	Las Vegas Prostate Cancer Center	Las Vegas	Nevada
United States	Las Vegas Urology - Cathedral Rock	Las Vegas	Nevada
United States	Las Vegas Urology - Pecos	Las Vegas	Nevada
United States	Las Vegas Urology - Smoke Ranch	Las Vegas	Nevada
United States	Las Vegas Urology - Sunset	Las Vegas	Nevada
United States	OptumCare Cancer Care at Charleston	Las Vegas	Nevada
United States	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada
United States	OptumCare Cancer Care at MountainView	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada
United States	Summerlin Hospital Medical Center	Las Vegas	Nevada
United States	Sunrise Hospital and Medical Center	Las Vegas	Nevada
United States	University Cancer Center	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Urology Specialists of Nevada - Central	Las Vegas	Nevada
United States	Urology Specialists of Nevada - Northwest	Las Vegas	Nevada
United States	Urology Specialists of Nevada - Southwest	Las Vegas	Nevada
United States	Beebe Medical Center	Lewes	Delaware
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Christiana Care Health System-Christiana Hospital	Newark	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	Northwestern Medicine Orland Park	Orland Park	Illinois
United States	Hope Cancer Care of Nevada-Pahrump	Pahrump	Nevada
United States	Mayo Clinic Hospital in Arizona	Phoenix	Arizona
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	Radiation Oncology Associates	Reno	Nevada
United States	Renown Regional Medical Center	Reno	Nevada
United States	Saint Mary's Regional Medical Center	Reno	Nevada
United States	Valley Medical Center	Renton	Washington
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	Carle Cancer Center	Urbana	Illinois
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware
United States	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington
United States	Rush-Copley Healthcare Center	Yorkville	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Biomarkers	The association of pre-treatment and on-treatment biomarkers in peripheral blood and in tumor tissues with response and time to recurrence, will be evaluated univariately through Chi-square test or log-rank test and through logistic regression model or Cox regression model with other prognostic factors adjusted.	Up to 5 years
Primary	Surgery Rate	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.	immediately after the completion of neoadjuvant immunotherapy and surgery
Primary	Progression free survival (PFS)	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.	At 12 months after initiation of neoadjuvant immunotherapy
Secondary	Incidence of adverse events	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.	Up to 5 years
Secondary	Objective response rate	Will be determined per modified RECIST. Response rate will be reported with 95% exact confidence interval.	Up to 5 years
Secondary	Major pathologic response	Defined as =< 10% residual viable tumor in the resected lung and lymph node tissue. Response rates will be reported with 95% exact confidence interval.	Up to 5 years
Secondary	Time to recurrence	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.	Time from surgery to disease relapse, progression, or second tumor, whichever occurs first, assessed up to 5 years