Trial record 1 of 1 for:
A092001
Chemotherapy With or Without Immunotherapy for Peritoneal Mesothelioma
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| ClinicalTrials.gov Identifier: NCT05001880 |
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Recruitment Status :
Recruiting
First Posted : August 12, 2021
Last Update Posted : March 23, 2023
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Sponsor:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
National Cancer Institute (NCI)
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Brief Summary:
This phase II trial compares the usual treatment alone to using immunotherapy (atezolizumab) plus the usual treatment in treating patients with peritoneal mesothelioma. The usual treatment consists of surgery or chemotherapy. Chemotherapy drugs, such as carboplatin and pemetrexed, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. 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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Peritoneal Malignant Mesothelioma | Biological: Atezolizumab Biological: Bevacizumab Procedure: Biospecimen Collection Drug: Carboplatin Procedure: Computed Tomography Procedure: Cytoreductive Surgery Drug: Hyperthermic Intraperitoneal Chemotherapy Drug: Pemetrexed Procedure: Positron Emission Tomography | Phase 2 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 66 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Phase 2 Randomized Trial of Neoadjuvant or Palliative Chemotherapy With or Without Immunotherapy for Peritoneal Mesothelioma |
| Actual Study Start Date : | October 15, 2021 |
| Estimated Primary Completion Date : | August 20, 2025 |
| Estimated Study Completion Date : | August 20, 2025 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Mesothelioma
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm I (carboplatin, pemetrexed, bevacizumab, atezolizumab)
Patients receive atezolizumab IV over 60 minutes, bevacizumab IV over 30-90 minutes, carboplatin IV over 30 minutes, and pemetrexed IV over 10 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 4-8 weeks, patients undergo cytoreductive surgery and HIPEC. Patients not eligible for surgery may receive atezolizumab and bevacizumab in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan and PET scan on study. Patients also undergo blood and tissue sample collection on study.
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Biological: Atezolizumab
Given IV
Other Names:
Biological: Bevacizumab Given IV
Other Names:
Procedure: Biospecimen Collection Undergo blood and tissue sample collection
Other Names:
Drug: Carboplatin Given IV
Other Names:
Procedure: Computed Tomography Undergo CT scan
Other Names:
Procedure: Cytoreductive Surgery Undergo surgery
Other Name: Cytoreduction Drug: Hyperthermic Intraperitoneal Chemotherapy Undergo HIPEC
Other Name: HIPEC Drug: Pemetrexed Given IV
Other Names:
Procedure: Positron Emission Tomography Undergo PET scan
Other Names:
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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. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 4-8 weeks, patients undergo cytoreductive surgery and HIPEC. Patients not eligible for surgery may receive bevacizumab with or without atezolizumab at the discretion of the investigator in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan and PET scan on study. Patients also undergo blood and tissue sample collection on study.
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Biological: Bevacizumab
Given IV
Other Names:
Procedure: Biospecimen Collection Undergo blood and tissue sample collection
Other Names:
Drug: Carboplatin Given IV
Other Names:
Procedure: Computed Tomography Undergo CT scan
Other Names:
Procedure: Cytoreductive Surgery Undergo surgery
Other Name: Cytoreduction Drug: Hyperthermic Intraperitoneal Chemotherapy Undergo HIPEC
Other Name: HIPEC Drug: Pemetrexed Given IV
Other Names:
Procedure: Positron Emission Tomography Undergo PET scan
Other Names:
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Primary Outcome Measures :
- Response rate [ Time Frame: Up to 4 years after study activation ]Will be compared between arms.
Secondary Outcome Measures :
- Major pathologic response rate [ Time Frame: Up to 3 years ]The proportion of patients with a pathologic response will be calculated and compared between arms and 95% confidence intervals reported. The chi-square test will be used to compare the rates between arms.
- Completeness of cytoreduction [ Time Frame: Up to 3 years ]Will be estimated.
- Conversion rate to surgical resection among those not deemed to be surgical candidates [ Time Frame: Up to 3 years ]Will estimate the conversion rate to surgical resection among those not deemed to be surgical candidates prior to treatment and provide the 95% confidence interval as well.
- Progression-free survival (PFS) [ Time Frame: From study entry to the first of either disease progression or death from any cause, where disease progression will be determined based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, assessed up to 3 years ]Will be estimated using the Kaplan-Meier method, where the log-rank test will be used to compare the 2 treatment arms.
- Overall survival [ Time Frame: From study entry to death from any cause, assessed up to 3 years ]Will be estimated using the Kaplan-Meier method, where the log-rank test will be used to compare the 2 treatment arms.
- Incidence of adverse events [ Time Frame: Up to 3 years ]The maximum grade for each type of adverse event will be summarized using Common Terminology Criteria for Adverse Events version 5.0. The frequency and percentage of grade 3+ adverse events will be compared between the 2 treatment arms. Comparisons between arms will be made by using either the Chi-square or Fisher's Exact test.
Other Outcome Measures:
- Soluble mesothelin-related peptides and megakaryocyte potentiating factor [ Time Frame: Up to 3 years ]Will be correlated with clinical endpoints including confirmed response, overall survival, PFS, recurrence, and adverse events. Statistical and graphical techniques will be used to explore the relationships between the translational and clinical data. For time-to-event endpoints, will use Cox proportional hazards models, and for confirmed response will use Logistic regression models. In addition, will use the Chi-square or Fisher's exact tests to test the association between categorical marker data and confirmed response/adverse events.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
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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
- All slides including performed immunostains from diagnostic tumor tissue together with pathology report for retrospective central pathology review
- 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
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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
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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 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
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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
Exclusion Criteria:
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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
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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
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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)
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05001880
Locations
Show 28 study locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Aaron S Mansfield | Alliance for Clinical Trials in Oncology |
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT05001880 |
| Other Study ID Numbers: |
NCI-2021-08573 NCI-2021-08573 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) A092001 ( Other Identifier: Alliance for Clinical Trials in Oncology ) A092001 ( Other Identifier: CTEP ) U10CA180821 ( U.S. NIH Grant/Contract ) |
| First Posted: | August 12, 2021 Key Record Dates |
| Last Update Posted: | March 23, 2023 |
| Last Verified: | December 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page. |
| URL: | https://grants.nih.gov/policy/sharing.htm |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Mesothelioma Mesothelioma, Malignant Adenoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms, Mesothelial Lung Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Pleural Neoplasms Lung Diseases Respiratory Tract Diseases Bevacizumab |
Antineoplastic Agents, Immunological Carboplatin Pemetrexed Atezolizumab Endothelial Growth Factors Antibodies Immunoglobulins Antibodies, Monoclonal Immunoglobulin G Antineoplastic Agents Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Physiological Effects of Drugs Growth Inhibitors |