Malignant Pleural Mesothelioma, Mesothelioma
Conditions
Keywords
MPM, Unresectable, Respiratory, Intrathoracic, Transarterial, Chemoperfusion
Brief summary
The purpose of this study is to determine whether the transarterial chemoperfusion treatment with cisplatin, methotrexate and gemcitabine is safe and effective in adults with malignant pleural mesothelioma (MPM).
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).
Interventions
DRUGCisplatin
The recommended dose of cisplatin for transarterial chemoperfusion in this study is 35 mg/m\^2 body surface area (BSA). During the lead in phase of the study, 3 patients will be treated with regular doses of cisplatin.
DRUGMethotrexate
The recommended dose of methotrexate for transarterial chemoperfusion in this study is 100 mg/m\^2 BSA. During the lead in phase of the study, 3 patients will be treated with 50% reduced dose of methotrexate (50 mg/m\^2).
DRUGGemcitabine
The recommended dose of gemcitabine for transarterial chemoperfusion in this study is 1000 mg/m\^2 BSA. During the lead in phase of the study, 3 patients will be treated with regular doses of gemcitabine.
OTHERLung Cancer Symptom Scale for Mesothelioma Questionnaire
Quality of life will be assessed using the modified version of the Lung Cancer Symptom Scale for Mesothelioma questionnaire.
Sponsors
H. Lee Moffitt Cancer Center and Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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 the patient refuses first line chemotherapy. * Have measurable disease, by computed tomography (CT) or magnetic resonance imaging (MRI) per modified Response Evaluation Criteria in Solid Tumors (RECIST) for mesothelioma. 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 \<2 (Karnofsky \>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
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | Up to 3 years | Disease control rate of transarterial chemoperfusion treatment with cisplatin, methotrexate and gemcitabine in patients with unresectable malignant pleural mesothelioma using modified Response Evaluation Criteria in Solid Tumors (RECIST) for mesothelioma. DCR provided as percentage of participants with partial response + percentage of participants with stable disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to 3 years | Overall survival defined as the time from the first day of transarterial chemoperfusion treatment to death. |
| Progression Free Survival (PFS) | Up to 3 years | 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 | Up to 3 years | Safety was assessed by monitoring adverse events and serious adverse events; the association with study treatment was assessed, and severity graded using Common Terminology Criteria for Adverse Events (CTCAE) v.4.03. Number of events that were Possible, Probable or Definitely related to study treatment. |
| Quality of Life Questionnaire Scores | Up to 3 years | 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. A higher number indicates more severe symptoms. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Chemoperfusion + Questionnaire Transarterial Chemoperfusion treatment with cisplatin (35 mg/m\^2), methotrexate (100 mg/m\^2) and gemcitabine (1000 mg/m\^2).
Patients undergo angiogram and transarterial chemoperfusion treatment in every 4 weeks (3-6 weeks interval allowed) when cisplatin, methotrexate and gemcitabine will be administered into the thoracic aorta and/or the internal mammary artery on the side of the disease.
Quality of life will be assessed using the modified version of the Lung Cancer Symptom Scale for Mesothelioma questionnaire.
Cisplatin: The recommended dose of cisplatin for transarterial chemoperfusion in this study is 35 mg/m\^2 body surface area (BSA). During the lead in phase of the study, 3 patients will be treated with regular doses of cisplatin.
Methotrexate: The recommended dose of methotrexate for transarterial chemoperfusion in this study is 100 mg/m\^2 BSA. During the lead in phase of the study, 3 patients will be treated with 50% reduced dose of methotrexate (50 mg/m\^2).
Gemcitabine: The recommended dose of gemcitabine for transarterial chemoperfusion in this study is 1000 mg/m\^2 BSA. During the lead in phase of the study, 3 patients will be treated with regular doses of gemcitabine.
Lung Cancer Symptom Scale for Mesothelioma Questionnaire: Quality of life will be assessed using the modified version of the Lung Cancer Symptom Scale for Mesothelioma questionnaire. | 34 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal prior to treatment | 2 | 0 |
Baseline characteristics
| Characteristic | Chemoperfusion + Questionnaire |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 30 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 34 Participants |
| Region of Enrollment United States | 34 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 5 | 21 / 25 |
| other Total, other adverse events | 5 / 5 | 25 / 25 |
| serious Total, serious adverse events | 2 / 5 | 7 / 25 |
Outcome results
Primary
Disease Control Rate (DCR)
Disease control rate of transarterial chemoperfusion treatment with cisplatin, methotrexate and gemcitabine in patients with unresectable malignant pleural mesothelioma using modified Response Evaluation Criteria in Solid Tumors (RECIST) for mesothelioma. DCR provided as percentage of participants with partial response + percentage of participants with stable disease.
Time frame: Up to 3 years
Population: All evaluable participants. Study patients cannot be analyzed separately. No dose limiting toxicities observed, therefore all participants received same dosing.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chemoperfusion + Questionnaire | Disease Control Rate (DCR) | 75 percentage of participants |
Secondary
Occurrence of Treatment Related Toxicity
Safety was assessed by monitoring adverse events and serious adverse events; the association with study treatment was assessed, and severity graded using Common Terminology Criteria for Adverse Events (CTCAE) v.4.03. Number of events that were Possible, Probable or Definitely related to study treatment.
Time frame: Up to 3 years
Population: All evaluable participants. Study patients cannot be analyzed separately. No dose limiting toxicities observed, therefore all participants received same dosing.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chemoperfusion + Questionnaire | Occurrence of Treatment Related Toxicity | 32 related adverse events |
Secondary
Overall Survival (OS)
Overall survival defined as the time from the first day of transarterial chemoperfusion treatment to death.
Time frame: Up to 3 years
Population: All evaluable participants. Study patients cannot be analyzed separately. No dose limiting toxicities observed, therefore all participants received same dosing.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chemoperfusion + Questionnaire | Overall Survival (OS) | 8.9 months |
Secondary
Progression Free Survival (PFS)
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).
Time frame: Up to 3 years
Population: All evaluable participants. Study patients cannot be analyzed separately. No dose limiting toxicities observed, therefore all participants received same dosing.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chemoperfusion + Questionnaire | Progression Free Survival (PFS) | 4.7 months |
Secondary
Quality of Life Questionnaire Scores
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. A higher number indicates more severe symptoms.
Time frame: Up to 3 years
Population: Quality of life questionnaires were not collected, therefore this measure cannot be analyzed.