Primary Outcome
- Objective Response Rate (ORR) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
Response rate, either Partial Response (PR) or Complete Response (CR) of transarterial chemoperfusion treatment with cisplatin, methotrexate and gemcitabine in patients with unresectable malignant pleural mesothelioma (MPM). CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to
Secondary Outcome Measures
- Overall Survival (OS) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
Overall survival defined as the time from the first day of transarterial chemoperfusion treatment to death. - Progression Free Survival (PFS) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
Progression free survival defined as the time from the first day of transarterial chemoperfusion treatment to disease progression based on imaging findings using modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria for mesothelioma. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). - Occurrence of Treatment Related Toxicity [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
Safety will be assessed by monitoring adverse events and serious adverse events; the association with study treatment will be assessed, and severity will be graded using Common Terminology Criteria for Adverse Events (CTCAE) v.4.03. - Quality of Life Questionnaire Scores [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
Quality of life will be assessed using the modified version of the Lung Cancer Symptom Scale for Mesothelioma questionnaire. Mesothelioma Symptom Scale includes 7 categories to rate on a scale of 1 to 10 regarding severity of symptoms during the last 24 hours.
Detailed Description:
This is an open-label, single arm, phase 2 study with a lead in safety cohort to evaluate the safety and efficacy of transarterial chemoperfusion treatment with cisplatin (35 mg/m2^), methotrexate (100 mg/m^2) and gemcitabine (1000 mg/m^2) in patients with unresectable MPM. During the lead in phase of the study, 3 patients will be treated with 50% reduced dose of methotrexate (50 mg/m^2) and regular doses of cisplatin (35 mg/m^2 body surface area (BSA)) and gemcitabine (1000 mg/m^2 BSA).
Eligibility
Criteria
- Inclusion Criteria
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- Must have histologically or cytologically confirmed malignant pleural mesothelioma (MPM).
- Have unresectable MPM or the patient refuses surgery for resectable MPM.
- Have failed to respond first line standard of care chemotherapy or chemotherapy suspended due to toxicity or other reasons.
- Have measurable disease, by computed tomography (CT) or magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Radiographic tumor assessment must be performed within 28 days prior to the first treatment.
- The predominant burden of disease lies in an arterial distribution which is accessible for transarterial chemoperfusion treatment.
- Eastern Cooperative Oncology Group (ECOG) performance status 60%).
- All baseline laboratory requirements will be assessed and should be obtained within 14 days of first treatment. Screening laboratory values must be met..
- Women participate in the study must be surgically sterile, post-menopausal, or women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation and after for a certain amount of time (up to 5 weeks) after the last treatment.
- Women must have a negative serum or urine pregnancy test within 24 hours prior to the start of transarterial chemoperfusion treatment.
- Men must be surgically sterile or must agree to use adequate contraception prior to study entry and for the duration of study participation and after for a certain amount of time (up to 14 weeks) after the last treatment.
- Ability to understand and the willingness to sign a written informed consent document.
- Participants must have signed and dated an Institutional Review Board (IRB) approved written informed consent form in accordance with regulatory and institutional guidelines.
- Must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, imaging studies, and other requirements of the study.
- This study permits the re-enrollment of a participant who has discontinued the study for a reason other than treatment failure or adverse event(s) of the study treatment.
- Exclusion Criteria:
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- Patients who have had chemotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Recovery means resolution to at least Grade 1 toxicity if there was no baseline toxicity or less than or equal to the patient’s baseline value.
- May not be receiving any other investigational agents.
- Known brain metastases or leptomeningeal metastases. Patients with other extrapleural metastases are included in this study.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to cisplatin, methotrexate, gemcitabine or other agents used during the study. History of allergic reaction to intravenous iodinated contrast media is not contraindication to the study. Patients with history of mild allergic reaction to iodinated contrast media will be premedicated with 40 mg of prednisone by mouth (p.o.) 12 and 2 hrs before the transarterial chemoperfusion treatment to prevent allergic reaction. Patients with history of moderate and severe allergic reaction to iodinated contrast media or patients with history of mild allergic reaction to iodinated contrast media despite adequate premedication will undergo angiogram using carbon dioxide or a gadolinium based contrast agent.
- Uncontrolled intercurrent illness including, but not limited to, presence of other malignancy, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Women who are pregnant or breastfeeding.
- HIV-positive patients receiving combination anti-retroviral therapy.
- Potential participants who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.
