Concurrent Pemetrexed/Cisplatin With Pleural Intensity Modulated Radiation Therapy for Patients With Unresectable Malignant Pleural Mesothelioma

NCT02639767 | Withdrawn Phase 1

• 1 other identifier: 15-304
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this study is to evaluate the safety of combining chemotherapy at different doses with a specific type of radiation therapy delivered to the entire lining of the lung to find out what effects, if any, it has on people. This radiation technique is called pleural intensity modulated radiation therapy (IMRT). IMRT specifically targets the lining of the lung (pleura) where the cancer is and reduces the risk of damaging the lung itself. When given after chemotherapy, pleural IMRT has demonstrated promising results with respect to keeping mesothelioma under control longer. However, the investigators want to determine if giving pleural IMRT at the same time as chemotherapy is safe. If safe, further studies will be done to see if chemotherapy and pleural IMRT given at the same time keeps the tumor under control for a longer period of time than chemotherapy followed by pleural IMRT.

Conditions

Malignant Pleural Mesothelioma

Keywords

Pemetrexed; Cisplatin; Intensity Modulated Radiation Therapy; 15-304

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicities (DLT)

  The NCI Common Terminology Criteria for Adverse Events version 4.0 will be used to grade toxicities during the trial. DLTs are defined as any of the following events occurring during and for the first 12 weeks after completing pleural IMRT

  up to 12 weeks

Study Arms (1)

pemetrexed/cisplatin with pleural IMRT

EXPERIMENTAL

This is a single institution phase I study of pemetrexed/cisplatin given concurrently with pleural intensity modulated radiation therapy (IMRT) in patients with unresectable malignant pleural mesothelioma (MPM). All patients will receive pleural intensity modulated radiation therapy (IMRT). Patients will be enrolled in cohorts of 3-6 at each dose level of pemetrexed/cisplatin, and dose escalation will proceed in a standard 3+3 fashion until the maximum tolerated dose (MTD) is identified.

Drug: Pemetrexed/Cisplatin; Radiation: Pleural Intensity Modulated Radiation Therapy; Device: MRI

Interventions

Pemetrexed/Cisplatin DRUG

Dose escalation of pemetrexed and cisplatin will follow the dose levels. The escalation will not exceed 500 mg/m\^2 for pemetrexed in combination with 75 mg/m\^2 of cisplatin even if the maximum tolerated dose is not identified. Each treatment cycle of chemotherapy will be 21 days. Patients will receive up to 2 cycles of chemotherapy during the radiation, and be followed for any DLT during the radiation therapy and for 12 weeks afterwards.

pemetrexed/cisplatin with pleural IMRT

Pleural Intensity Modulated Radiation Therapy RADIATION

Pleura intensity modulated radiation therapy (IMRT) will be administered over approximately 6 weeks at 50.4 Gy in 28 fractions. The prescription radiation dose may anywhere between 45 and 50.4 Gy in 25 fractions if necessary to meet the normal tissue dose constraints.

pemetrexed/cisplatin with pleural IMRT

MRI DEVICE

A pre-treatment MRI before chemo-RT will be acquired and will be used for target delineation. A three month post-treatment MRI will be acquired with the same protocol to assess the response from concurrent chemo-RT.

pemetrexed/cisplatin with pleural IMRT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically confirmed diagnosis of malignant pleural mesothelioma at MSKCC
• No plans for surgical resection
• Stage T1-4, N0-3, M0
• No prior radiation therapy to the chest, breast or supraclavicular fossa that would limit radiation delivery to the full prescription dose
• Prior chemotherapy regimens ≤1
• Age ≥18 years
• Karnofsky performance status ≥ 80%
• Pulmonary function tests as follows: DLCO\>50% predicted
• Adequate hematologic, hepatic, and renal function as indicated by the following laboratory values
• Absolute neutrophil count ≥ 1,500/mcL
• Platelets ≥ 100,000/mcL
• Calculated creatinine clearance (CrCl) ≥ 45mL/min (using Cockcroft \& Gault method)
• Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) (unless known Gilbert's disease)
• AST (SGOT) and ALT (SGPT) ≤ 3.0 x ULN

You may not qualify if:

• Pregnant or lactating women, or men or women not using effective contraception
• Patients with an active infection that requires systemic antibiotics, antiviral, or antifungal treatments
• Patients with a concurrent active malignancy (with the exception of skin cancer)
• Patients with serious unstable medical illness
• Patients with idiopathic pulmonary fibrosis
• Patients with NYHA heart failure class \>2
• Patients with only one kidney that is ipsilateral to the mesothelioma
• Implanted pacemaker and/or defibrillator ipsilateral to the mesothelioma if it cannot be moved
• Metallic implant, e.g. pacemaker, defibrillator
• Unmanageable claustrophobia
• High risk for nephrogenic systemic fibrosis

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (6)

Memorial Sloan Kettering at Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Cancer Center @ Suffolk

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering West Harrison

East White Plains, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering at Mercy Medical Center

Rockville Centre, New York, United States

Location

Memoral Sloan Kettering Cancer Center at Phelps

Sleepy Hollow, New York, 10591, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

Pemetrexed; Cisplatin

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

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

• Marjorie Zauderer

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2015
• First Posted: December 24, 2015
• Study Start: December 1, 2015
• Primary Completion: December 1, 2016
• Last Updated: December 7, 2016

Record last verified: 2016-12

Locations

US (6)