Transarterial Chemoperfusion: Cisplatin, Methotrexate, Gemcitabine for Unresectable Pleural Mesothelioma

Status: Active

Description

This phase II trial studies how well cisplatin, methotrexate, and gemcitabine hydrochloride given via transarterial perfusion work in treating patients with malignant pleural mesothelioma that cannot be removed by surgery. Drugs used in chemotherapy, such as cisplatin, methotrexate, and gemcitabine hydrochloride, 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. Transarterial chemoperfusion is a procedure that allows chemotherapy agents, such as cisplatin, methotrexate and gemcitabine hydrochloride, to be directly injected into the arteries that supply blood to the area where the tumor is located. Transarterial chemoperfusion with cisplatin, methotrexate, and gemcitabine hydrochloride may be an effective treatment for malignant pleural mesothelioma.

Eligibility Criteria

Inclusion Criteria

  • Patients must have histologically or cytologically confirmed malignant pleural mesothelioma (MPM)
  • Patients have unresectable MPM or the patient refuses surgery for resectable MPM
  • Patients who failed to respond first line standard of care chemotherapy or chemotherapy suspended due to toxicity or other reasons
  • Patients who are refusing first line standard of care chemotherapy
  • Patients must have measurable disease, by computed tomography (CT) or magnetic resonance imaging (MRI) per modified RECIST criteria 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%)
  • Leukocytes >= 3,000/uL obtained within 14 days of first treatment
  • Absolute neutrophil count >= 1,500/uL obtained within 14 days of first treatment
  • Platelets >= 100,000/uL obtained within 14 days of first treatment
  • Prothrombin time =< 1.5 x upper limit of normal (ULN) obtained within 14 days of first treatment
  • Partial thromboplastin time =< 1.5 x institutional ULN obtained within 14 days of first treatment
  • Total bilirubin =< 1.5 x ULN; except subjects with Gilbert syndrome who can have total bilirubin < 3.0 mg/dL) obtained within 14 days of first treatment
  • Aspartate aminotransferase =< 2.5 x institutional ULN obtained within 14 days of first treatment
  • Alanine aminotransferase =< 2.5 x institutional ULN obtained within 14 days of first treatment
  • Alkaline phosphatase =< 2.5 x institutional ULN obtained within 14 days of first treatment
  • Creatinine within normal institutional limits OR creatinine clearance >= 50 mL/min based on the standard Cockcroft and Gault formula obtained within 14 days of first treatment
  • 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 * The individual methods of contraception and duration should be determined in consultation with the investigator; the duration of mandatory contraception is based on clearance of the investigational drug (5 half-lives after treatment completion); for women, an additional 30 days is required to complete an ovulatory cycle; calculation of duration of mandatory contraception: the half-life of cisplatin is 20-30 minutes, half-life of methotrexate is 8-15 hours and half-life of gemcitabine is 42-94 minutes; thus, contraception is required for up to 5 weeks after the last treatment for women of child-bearing potential * Women must have a negative serum or urine pregnancy test within 24 hours prior to the start of transarterial chemoperfusion treatment * Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Men participate in the study 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 (as defined below); the investigator shall review contraception methods and the time period that contraception must be followed; the duration of mandatory contraception is based on clearance of the investigational drug (5 half-lives after treatment completion); for males, an additional 90 days is required to complete turnover of drug-exposed sperm; calculation of duration of mandatory contraception: the half-life of cisplatin is 20-30 minutes, half-life of methotrexate is 8-15 hours and half-life of gemcitabine is 42-94 minutes; thus, contraception for men is required for up to 14 weeks after the last treatment
  • Ability to understand and the willingness to sign a written informed consent document
  • Patients must have signed and dated an Institutional Review Board (IRB) approved written informed consent form in accordance with regulatory and institutional guidelines; this must be obtained before the performance of any protocol related procedures that are not part of normal subject care
  • Subjects 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 patient who has discontinued the study for a reason other than treatment failure or adverse event(s) of the study treatment; the patient must be re-consented and assigned a new subject number

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
  • Patients may not be receiving any other investigational agents
  • Patients with known brain metastases or leptomeningeal metastases should be excluded from this clinical trial; 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 orally (p.o.) 12 and 2 hours (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 are excluded from the study
  • Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study
  • Prisoners or subjects who are involuntarily incarcerated
  • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness

Locations & Contacts

Florida

Tampa
Moffitt Cancer Center
Status: Active
Contact: Bela Kis
Phone: 813-745-8425
Email: bela.kis@moffitt.org

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the disease control rate of transarterial chemoperfusion treatment with cisplatin, methotrexate and gemcitabine (gemcitabine hydrochloride) in patients with unresectable malignant pleural mesothelioma using modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria for mesothelioma.

SECONDARY OBJECTIVES:

I. To assess overall survival (OS) in patients with malignant pleural mesothelioma treated with transarterial chemoperfusion.

II. To assess progression free survival (PFS), defined as the time from the first day of cisplatin, methotrexate and gemcitabine transarterial chemoperfusion treatment to disease progression (either pleural or extrapleural), based on imaging findings using modified RECIST criteria for mesothelioma or death from any cause.

III. To determine the severity and frequency of adverse events related to transarterial chemoperfusion with cisplatin, methotrexate and gemcitabine during the chemoperfusion phase and follow-up phase of the study.

IV. To assess quality of life in patients with malignant pleural mesothelioma treated with transarterial chemoperfusion.

OUTLINE:

Patients undergo angiogram and transarterial chemoperfusion with cisplatin, methotrexate, and gemcitabine hydrochloride every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 weeks and then every 2 months thereafter.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Moffitt Cancer Center

Principal Investigator
Bela Kis

Trial IDs

Primary ID MCC-18094
Secondary IDs NCI-2016-00002, MCC # 18094, MCC 18094
Clinicaltrials.gov ID NCT02611037