Heated Pemetrexed Disodium and Cisplatin during Surgery in Treating Participants with Pleural Malignant Mesothelioma

Status: Active

Description

This phase I trial studies the side effects and best dose of heated pemetrexed disodium when given together with heated cisplatin during surgeries such as extrapleural pneumonectomy or pleural decortication in treating participants with pleural malignant mesothelioma. Pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin, 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. Heating pemetrexed disodium and cisplatin and infusing them directly into the chest during the surgery may kill more tumor cells.

Eligibility Criteria

Inclusion Criteria

  • Histologically proven malignant pleural mesothelioma MPM that is considered resectable according to the following criteria: * Confined to one pleural space * No chest wall invasion * No transdiaphragmatic involvement * No invasion of mediastinal structures
  • Eastern Cooperative Oncology Group performance status 0-1
  • Adequate cardiopulmonary reserve defined as follows as assessed within 4 months of study entry: * Predicted postoperative forced expiratory volume FEV1 > 1L * Normal left ventricular function (ejection fraction EF ≥ 45%) and right ventricular function * No pulmonary hypertension noted on preoperative transthoracic echocardiography
  • Completed within 60 days of surgery: Hemoglobin ≥ 9.0 g/dL
  • Completed within 60 days of surgery: Absolute neutrophil count (ANC) ≥ 1500/mm^3
  • Completed within 60 days of surgery: Platelet count ≥ 100,000/mm
  • Completed within 60 days of surgery: Calculated creatinine clearance ≥ 60 mL/min; the creatinine clearance CrCl is determined by the Cockcroft-Gault formula
  • Completed within 60 days of surgery: Total bilirubin < 1.5 times the upper limit of institutional normal value
  • Completed within 60 days of surgery: Aspartate aminotransferase AST (serum glutamic oxaloacetic transaminase SGOT) and alanine aminotransferase ALT (serum glutamic pyruvic transaminase SGPT) < 3 times the upper limit of the institutional normal
  • Completed within 60 days of surgery: International normalized ratio INR ≤ 1.5 in patients not utilizing systemic anticoagulation as part of their medical regimen
  • Women of child bearing potential and sexually active males must use an accepted and effective non-hormonal method of contraception
  • Patients must be deemed by the investigators to be fully recovered from both acute and late effects of any prior surgery, radiotherapy, or other antineoplastic therapy
  • Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
  • The ability to interrupt non-steroidal anti-inflammatory drugs NSAIDS 2 days before (5 days for long-acting NSAIDs), the day of, and 2 days following administration of pemetrexed
  • The ability to take folic acid, vitamin B12, and dexamethasone according to protocol

Exclusion Criteria

  • Not pregnant or breastfeeding; a negative pregnancy test is required within 14 days of registration for pre- or perimenopausal (i.e., last menstrual period within one year of registration) women
  • Patients with a history of another neoplasm, with the exception of non-metastatic, non-melanoma skin cancers, carcinoma in situ of the cervix, or cancer cured by surgery or small field radiotherapy, within 5 years of registration will be excluded
  • Patients with uncontrolled cardiovascular disease (a history of hospitalization for acute myocardial infarction, arrhythmia, or congestive heart failure within 3 months prior to registration) will be excluded
  • Registered patients with an active infection or with a fever of ≥ 38.5 Celsius degrees (C) within 24 hours of the first scheduled day of protocol initiation will be excluded until their infection and/or fever resolves
  • Any other medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient’s ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results
  • Inability to interrupt use of non-steroidal anti-inflammatory drugs (NSAIDS)
  • Peripheral neuropathy ≥ grade 2 (Common Terminology Criteria for Adverse Events CTCAE)
  • Systemic chemotherapy within 3 weeks of registration
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to cisplatin and pemetrexed
  • Presence of third space fluid which cannot be controlled by drainage

Locations & Contacts

Texas

Houston
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: Active
Contact: Shawn S. Groth
Phone: 713-798-6281
Email: Shawn.Groth@bcm.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of intrathoracic administration of pemetrexed disodium (pemetrexed) when given in conjunction with cisplatin in patients with resectable malignant pleural mesothelioma (MPM).

SECONDARY OBJECTIVES:

I. To determine the toxicity and grades associated with cytoreductive surgery and heated intraoperative chemotherapy HIOC with cisplatin and pemetrexed in patients with resectable malignant pleural mesothelioma MPM.

II. To assess overall survival and progression-free survival after pleural decortication PD or extrapleural pneumonectomy EPP and heated intraoperative chemotherapy HIOC with cisplatin and pemetrexed for malignant pleural mesothelioma MPM.

CORRELATIVE OBJECTIVES:

I. To characterize the pharmacokinetics and pharmacodynamics of pemetrexed when administered as a hyperthermic intrathoracic lavage after pleural decortication PD or extrapleural pneumonectomy EPP.

II. To determine whether the degree of thymidylate synthase and excision repair cross-complementing group 1 ERCC1 gene expression in malignant pleural mesothelioma MPM tissue correlates with clinical response to pemetrexed.

OUTLINE: This is a dose-escalation study of pemetrexed.

Participants receive heated pemetrexed via intrathoracic infusion over 60 minutes and heated cisplatin via intrathoracic infusion over 60 minutes during EPP or PD surgery.

After completion of study treatment, participants are followed up periodically.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center

Principal Investigator
Shawn S. Groth

Trial IDs

Primary ID HIOC-H-36460
Secondary IDs NCI-2018-00722
Clinicaltrials.gov ID NCT02838745