Study of Cytoreductive Surgery and Hyperthermic Intraoperative Chemotherapy With Pemetrexed and Cisplatin for MPM

NCT02838745 | Terminated Phase 1

• 1 other identifier: H-36460
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objective To determine the maximum tolerated dose (MTD) of intrathoracic administration of pemetrexed when given in conjunction with cisplatin in patients with resectable malignant pleural mesothelioma MPM. Secondary Objectives To determine the toxicity and grades associated with cytoreductive surgery and Hyperthermic Intraoperative Chemotherapy HIOC with cisplatin and pemetrexed in patients with resectable MPM. To assess overall survival and progression-free survival after PD or EPP and HIOC with cisplatin and pemetrexed for MPM Correlative Objectives To characterize the pharmacokinetics and pharmacodynamics of pemetrexed when administered as a hyperthermic intrathoracic lavage after PD or EPP To determine whether the degree of thymidylate synthase and ERCC1 gene expression in MPM tissue correlates with clinical response to pemetrexed.

Conditions

Mesothelioma

Outcome Measures

Primary Outcomes (1)

• Number of participants with Dose-Limiting Toxicity (DLT)

  Dose limiting toxicity (DLT) is defined as: 1) Grade 4 treatment-related hematologic toxicity that lasts more than for 5 days or grade 3 thrombocytopenia with grade 3 or 4 bleeding, 2) Febrile neutropenia, 3) Grade 3 or greater treatment related non-hematologic toxicity with the following exceptions:Grade 3 diarrhea is a dose limiting toxicity DLT only if the patient was compliant with an anti-diarrheal program consistent with best clinical practice; Grade 3 or 4 nausea and vomiting is a dose limiting toxicity DLT only if the patient was compliant with an antiemetic program consistent with best clinical practice; Alopecia

  from the first day of treatment until 4 weeks after the treatment

Study Arms (2)

Pemetrexed (300 mg/m2) and Cisplatin (175 mg/m2)

EXPERIMENTAL

Pemetrexed and cisplatin will be admixed together in 1 liter of normal saline. The admixture of pemetrexed/cisplatin is stable for 4 hours and should be prepared and delivered immediately before use in the OR. The length of the pemetrexed/cisplatin lavage will be 1 hour.

Drug: Pemetrexed; Drug: Cisplatin

Pemetrexed (400 mg/m2) and Cisplatin (175 mg/m2)

EXPERIMENTAL

Pemetrexed and cisplatin will be admixed together in 1 liter of normal saline. The admixture of pemetrexed/cisplatin is stable for 4 hours and should be prepared and delivered immediately before use in the OR. The length of the pemetrexed/cisplatin lavage will be 1 hour.

Drug: Pemetrexed; Drug: Cisplatin

Interventions

Pemetrexed DRUG

Pemetrexed (300 mg/m2) and Cisplatin (175 mg/m2); Pemetrexed (400 mg/m2) and Cisplatin (175 mg/m2)

Cisplatin DRUG

Pemetrexed (300 mg/m2) and Cisplatin (175 mg/m2); Pemetrexed (400 mg/m2) and Cisplatin (175 mg/m2)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Age ≥ 18 years
• Eastern Cooperative Oncology Group performance status 0-1 (Appendix A)
• 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
• Must have adequate hematologic, renal and hepatic function as defined by the following laboratory values (completed within 60 days of surgery) Hematologic: Hemoglobin ≥ 9.0 g/dL, absolute neutrophil count (ANC) ≥ 1500/mm3, platelet count ≥ 100,000/mm Renal: Calculated creatinine clearance ≥ 60 mL/min
• The creatinine clearance CrCl is determined by the Cockcroft-Gault formula:
• Males:
• Creatinine Clearance CrCl (mL)/min) = weight (kg) x (140-age) 72 x serum creatinine (mg/dL)

You may not qualify if:

• Not pregnant or breastfeeding - the drugs used in this study are Pregnancy Category D (clear evidence of risk in pregnancy). 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°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
• Prior Allergies: 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.

Sponsors & Collaborators

• Baylor College of Medicine: lead

Study Sites (1)

Baylor St Lukes

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Mesothelioma

Interventions

Pemetrexed; Cisplatin

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Shawn Groth, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: July 16, 2016
• First Posted: July 20, 2016
• Study Start: September 1, 2016
• Primary Completion: September 5, 2019
• Study Completion: September 5, 2019
• Last Updated: March 31, 2022

Record last verified: 2022-03

Locations

US (1)