| Eligibility |
Inclusion Criteria:
- 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
- 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 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
Exclusion 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)
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