Recruiting
Phase 2

Chemotherapy & Immunotherapy

Sponsor:

National Cancer Institute (NCI)

Code:

NCT05001880

Conditions

Peritoneal Malignant Mesothelioma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Atezolizumab

Bevacizumab

Biospecimen Collection

Carboplatin

Computed Tomography

Study Details

Brief summary:

This phase II trial compares the usual treatment alone (carboplatin, pemetrexed, and bevacizumab) to using immunotherapy (atezolizumab) plus the usual treatment in treating patients with peritoneal mesothelioma. The usual treatment consists of surgery or chemotherapy. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Pemetrexed is in a class of medications called antifolate antineoplastic agents. It works by stopping cells from using folic acid to make deoxyribonucleic acid and may kill cancer cells. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving atezolizumab with usual treatment may work better than usual treatment alone.

Conditions

Peritoneal Malignant Mesothelioma

Study ID

NCT05001880

Start date

Mar 22, 2022

Status verified date

Aug, 2026

Completion date

Aug 1, 2027

Anticipated

Primary completion date

Aug 1, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Physicians should consider whether any of the following may render the patient inappropriate for this protocol:

  • Psychiatric illness which would prevent the patient from giving informed consent
  • Medical conditions such as uncontrolled infection, uncontrolled diabetes mellitus or cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient

  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Patients with a "currently active" second malignancy other than non-melanoma skin cancers or cervical carcinoma in situ. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for >= 3 years
  • In addition:

  • Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial. Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives or double barrier method (diaphragm plus condom)

  • A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
  • Histologically or cytologically confirmed malignant peritoneal mesothelioma for which there has been no prior treatment. Given the indolent nature of well-differentiated papillary mesothelioma and multicystic mesothelioma, patients with these variants are not eligible for participation
  • Must have measurable disease per RECIST version (v) 1.1
  • Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative pregnancy test done =< 28 days prior to registration is required
  • Age >= 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Leukocytes >= 2,500/mm\^3
  • Absolute neutrophil count (ANC) >= 1,500/mm\^3
  • Platelet count >= 100,000/mm\^3
  • Creatinine clearance >= 45 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) =< 3.0 x upper limit of normal (ULN)
  • Urine protein/creatinine (UPC) ratio < 1, or urine protein: =< 1+
  • No prior systemic therapy for peritoneal mesothelioma is allowed. No concurrent radiotherapy is allowed
  • No active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, or multiple sclerosis, with the following exceptions:

  • Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study
  • Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study
  • Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:

  • Rash must cover < 10% of body surface area
  • Disease is well controlled at baseline and requires only low-potency topical corticosteroids
  • No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
  • No history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
  • No prior allogeneic stem cell or solid organ transplantation
  • Central nervous system (CNS) metastases must have been treated with local therapy (surgery, radiation, ablation) with systemic steroids tapered to a physiologic dose (10 mg or prednisone equivalent or less)
  • Patients who have received live attenuated vaccines within 30 days of the first dose of trial treatment are eligible at the discretion of the investigator. All seasonal influenza vaccines and vaccines intended to prevent SARS-CoV-2 and coronavirus disease 2019 (COVID-19) are allowed
  • No history of inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg)
  • No history of hypertensive crisis or hypertensive encephalopathy
  • No clinically significant cardiovascular disease, such as cerebrovascular accidents within 12 months prior to randomization, myocardial infarction within 12 months prior to randomization, unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure (CHF), or serious cardiac arrhythmia uncontrolled by medication or potentially interfering with study treatment
  • No significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months prior to randomization
  • No history of grade >= 4 venous thromboembolism
  • No history or evidence upon physical or neurological examination of central nervous system disease (e.g. seizures) unrelated to cancer unless adequately treated with standard medical therapy
  • No history of grade >= 2 hemoptysis (defined as >= 2.5 mL of bright red blood per episode) within 1 month prior to screening
  • No history or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e., in the absence of therapeutic anticoagulation)
  • No major surgical procedure or significant traumatic injury within 28 days prior to initiation of study treatment (diagnostic laparoscopy is allowed as part of diagnosing peritoneal mesothelioma)
  • No core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to initiation of study treatment
  • Placement of a vascular access device should be at least 2 days prior to initiation of study treatment
  • No active infection requiring IV antibiotics at the time of initiation of study treatment
  • No history of abdominal fistula, gastrointestinal (GI) perforation, intra-abdominal abscess, or active GI bleeding within 6 months prior to randomization
  • No serious, non-healing wound, active ulcer, or untreated bone fracture
  • No other malignancy within 5 years prior to randomization, except for localized cancer in situ, such as basal or squamous cell skin cancer
  • Patients with a creatinine clearance between 45 and 79 mL/min should not use ibuprofen or other nonsteroidal anti-inflammatory drug (NSAIDs) for 2 days before, the day of, and 2 days following pemetrexed administration
  • No treatment with immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-alpha agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:

  • Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) may be eligible for the study
  • Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study

Study Design

Enrollment

66 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm I (carboplatin, pemetrexed, bevacizumab, atezolizumab)

Patients receive atezolizumab IV over 30-60 minutes, bevacizumab IV over 30-90 minutes, carboplatin IV over 30 minutes, and pemetrexed IV over 10 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 4-8 weeks, patients then undergo cytoreductive surgery and HIPEC. Patients not eligible for surgery may receive atezolizumab IV over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 1 of each maintenance therapy cycle. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan, PET scan, and collection of blood and tissue samples throughout the study.

active comparator: Arm II (carboplatin, pemetrexed, bevacizumab)

Patients receive bevacizumab IV over 30-90 minutes, carboplatin IV over 30 minutes, and pemetrexed IV over 10 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 4-8 weeks, patients then undergo cytoreductive surgery and HIPEC. Patients not eligible for surgery may receive bevacizumab IV over 30-90 minutes with or without atezolizumab IV over 30-60 minutes on day 1 of each maintenance therapy cycle at the discretion of the investigator. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan, PET scan, and collection of blood and tissue samples throughout the study.

Interventions

Atezolizumab

Given IV

Bevacizumab

Given IV

Biospecimen Collection

Undergo blood and tissue sample collection

Carboplatin

Given IV

Computed Tomography

Undergo CT scan

Cytoreductive Surgery

Undergo surgery

Hyperthermic Intraperitoneal Chemotherapy

Undergo HIPEC

Pemetrexed

Given IV

Positron Emission Tomography

Undergo PET scan

Primary outcome measure

  • Response rate [ Time Frame: Up to 4 years after study activation ]

Central Contacts and Locations

Locations

Alliance for Clinical Trials in Oncology

Recruiting

Chicago, Illinois, United States, 60606

Contacts

Aaron S. Mansfield

507-293-0569mansfield.aaron@mayo.edu

Principal Investigator:

Aaron S. Mansfield

University of Chicago Comprehensive Cancer Center

Recruiting

Chicago, Illinois, United States, 60637

Contacts

Site Public Contact

773-702-8222cancerclinicaltrials@bsd.uchicago.edu

Principal Investigator:

Hedy L. Kindler

Carle at The Riverfront

Recruiting

Danville, Illinois, United States, 61832

Contacts

Site Public Contact

800-446-5532Research@Carle.com

Principal Investigator:

Suparna Mantha

Carle Physician Group-Effingham

Recruiting

Effingham, Illinois, United States, 62401

Contacts

Site Public Contact

800-446-5532Research@carle.com

Principal Investigator:

Suparna Mantha

Carle Physician Group-Mattoon/Charleston

Recruiting

Mattoon, Illinois, United States, 61938

Contacts

Site Public Contact

800-446-5532Research@carle.com

Principal Investigator:

Suparna Mantha

Carle Cancer Center

Recruiting

Urbana, Illinois, United States, 61801

Contacts

Site Public Contact

800-446-5532Research@carle.com

Principal Investigator:

Suparna Mantha

The Carle Foundation Hospital

Recruiting

Urbana, Illinois, United States, 61801

Contacts

Site Public Contact

800-446-5532Research@carle.com

Principal Investigator:

Suparna Mantha

Sanford Joe Lueken Cancer Center

Recruiting

Bemidji, Minnesota, United States, 56601

Contacts

Site Public Contact

218-333-5000OncologyClinicalTrialsFargo@sanfordhealth.org

Principal Investigator:

Daniel Almquist

Mercy Hospital

Recruiting

Coon Rapids, Minnesota, United States, 55433

Contacts

Site Public Contact

952-993-1517mmcorc@healthpartners.com

Principal Investigator:

Yan Ji

Fairview Southdale Hospital

Recruiting

Edina, Minnesota, United States, 55435

Contacts

Site Public Contact

952-993-1517mmcorc@healthpartners.com

Principal Investigator:

Yan Ji

Abbott-Northwestern Hospital

Recruiting

Minneapolis, Minnesota, United States, 55407

Contacts

Site Public Contact

952-993-1517mmcorc@healthpartners.com

Principal Investigator:

Yan Ji

Mayo Clinic in Rochester

Recruiting

Rochester, Minnesota, United States, 55905

Contacts

Site Public Contact

855-776-0015

Principal Investigator:

Aaron S. Mansfield

Park Nicollet Clinic - Saint Louis Park

Recruiting

Saint Louis Park, Minnesota, United States, 55416

Contacts

Site Public Contact

952-993-1517mmcorc@healthpartners.com

Principal Investigator:

Yan Ji

Regions Hospital

Recruiting

Saint Paul, Minnesota, United States, 55101

Contacts

Site Public Contact

952-993-1517mmcorc@healthpartners.com

Principal Investigator:

Yan Ji

United Hospital

Recruiting

Saint Paul, Minnesota, United States, 55102

Contacts

Site Public Contact

952-993-1517mmcorc@healthpartners.com

Principal Investigator:

Yan Ji

Rice Memorial Hospital

Recruiting

Willmar, Minnesota, United States, 56201

Contacts

Site Public Contact

952-993-1517mmcorc@healthpartners.com

Principal Investigator:

Yan Ji

Sanford Cancer Center Worthington

Recruiting

Worthington, Minnesota, United States, 56187

Contacts

Site Public Contact

605-312-3320

Principal Investigator:

Daniel Almquist

Sanford Bismarck Medical Center

Recruiting

Bismarck, North Dakota, United States, 58501

Contacts

Site Public Contact

701-323-5760OncologyClinicalTrialsFargo@sanfordhealth.org

Principal Investigator:

Daniel Almquist

Sanford Broadway Medical Center

Recruiting

Fargo, North Dakota, United States, 58122

Contacts

Site Public Contact

701-323-5760OncologyClinicalTrialsFargo@sanfordhealth.org

Principal Investigator:

Daniel Almquist

Sanford Roger Maris Cancer Center

Recruiting

Fargo, North Dakota, United States, 58122

Contacts

Site Public Contact

701-234-6161OncologyClinicalTrialsFargo@sanfordhealth.org

Principal Investigator:

Daniel Almquist

Ohio State University Comprehensive Cancer Center

Recruiting

Columbus, Ohio, United States, 43210

Contacts

Site Public Contact

800-293-5066Jamesline@osumc.edu

Principal Investigator:

John L. Hays

University of Oklahoma Health Sciences Center

Recruiting

Oklahoma City, Oklahoma, United States, 73104

Contacts

Site Public Contact

405-271-8777ou-clinical-trials@ouhsc.edu

Principal Investigator:

Hassan Hatoum

UPMC Hillman Cancer Center

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Contacts

Site Public Contact

412-647-8073

Principal Investigator:

Liza C. Villaruz

Sanford Cancer Center Oncology Clinic

Recruiting

Sioux Falls, South Dakota, United States, 57104

Contacts

Site Public Contact

605-312-3320OncologyClinicTrialsSF@sanfordhealth.org

Principal Investigator:

Daniel Almquist

Sanford USD Medical Center - Sioux Falls

Recruiting

Sioux Falls, South Dakota, United States, 57117-5134

Contacts

Site Public Contact

605-312-3320OncologyClinicalTrialsSF@SanfordHealth.org

Principal Investigator:

Daniel Almquist

UT MD Anderson - The Woodlands

Recruiting

Conroe, Texas, United States, 77384

Contacts

Site Public Contact

866-632-6789askmdanderson@mdanderson.org

Principal Investigator:

Kanwal P. Raghav

UT MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

Site Public Contact

866-632-6789askmdanderson@mdanderson.org

Principal Investigator:

Kanwal P. Raghav

UT MD Anderson - West Houston

Recruiting

Houston, Texas, United States, 77079

Contacts

Site Public Contact

877-632-6789askmdanderson@mdanderson.org

Principal Investigator:

Kanwal P. Raghav

UT MD Anderson - League City

Recruiting

League City, Texas, United States, 77573

Contacts

Site Public Contact

877-632-6789askmdanderson@mdanderson.org

Principal Investigator:

Kanwal P. Raghav

UT MD Anderson - Sugar Land

Recruiting

Sugar Land, Texas, United States, 77478

Contacts

Site Public Contact

877-632-6789askmdanderson@mdanderson.org

Principal Investigator:

Kanwal P. Raghav

ThedaCare Regional Cancer Center

Recruiting

Appleton, Wisconsin, United States, 54911

Contacts

Site Public Contact

920-364-3604ResearchDept@thedacare.org

Principal Investigator:

Matthias Weiss

Marshfield Medical Center-EC Cancer Center

Recruiting

Eau Claire, Wisconsin, United States, 54701

Contacts

Site Public Contact

800-782-8581oncology.clinical.trials@marshfieldresearch.org

Principal Investigator:

Michael Husak

Marshfield Medical Center-Marshfield

Recruiting

Marshfield, Wisconsin, United States, 54449

Contacts

Site Public Contact

800-782-8581oncology.clinical.trials@marshfieldresearch.org

Principal Investigator:

Michael Husak

Marshfield Medical Center - Minocqua

Recruiting

Minocqua, Wisconsin, United States, 54548

Contacts

Site Public Contact

800-782-8581oncology.clinical.trials@marshfieldresearch.org

Principal Investigator:

Michael Husak

Marshfield Medical Center-Rice Lake

Recruiting

Rice Lake, Wisconsin, United States, 54868

Contacts

Site Public Contact

800-782-8581oncology.clinical.trials@marshfieldresearch.org

Principal Investigator:

Michael Husak

Marshfield Medical Center-River Region at Stevens Point

Recruiting

Stevens Point, Wisconsin, United States, 54482

Contacts

Site Public Contact

800-782-8581oncology.clinical.trials@marshfieldresearch.org

Principal Investigator:

Michael Husak

Marshfield Medical Center - Weston

Recruiting

Weston, Wisconsin, United States, 54476

Contacts

Site Public Contact

800-782-8581oncology.clinical.trials@marshfieldresearch.org

Principal Investigator:

Michael Husak

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Aug 13, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-08-13.