Study Using Chemotherapy +/- Pleurectomy/Decortication Followed By Intensity Modulated Radiation Therapy

This study is currently recruiting participants.
Verified February 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborators:
Eli Lilly and Company
M.D. Anderson Cancer Center
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00715611
First received: July 11, 2008
Last updated: February 10, 2014
Last verified: February 2014
  Purpose

For patients with this type of cancer, the standard of care is treatment with chemotherapy. Radiation therapy is typically not used. This is because radiation to the entire lining of the lung has many side effects that are often severe including damage to the lung (pneumonitis). There is a new radiation technique using Intensity Modulated Radiation Therapy (IMRT) that has been shown to reduce many of the side effects of standard radiation therapy. This type of radiation therapy specifically targets the lining of the lung, where you have your cancer, and reduces the risk of damaging the lung itself. The purpose of this study is to test the safety and toxicity of standard chemotherapy +/-pleurectomy/decortication followed by IMRT to the pleura in patients with malignant pleural mesothelioma.


Condition Intervention Phase
Mesothelioma
Other: Pemetrexed + Cisplatin or Carboplatin AUC=5 Pleurectomy/decortication (if feasible) Intensity Modulated Radiation Therapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Toxicity Study Using Chemotherapy +/- Pleurectomy/Decortication Followed By Intensity Modulated Radiation Therapy to the Pleura in Patients With Locally Advanced Malignant Pleural Mesothelioma.

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • To determine the safety of chemotherapy +/- pleurectomy/decortication followed by IMRT to the pleura in patients with malignant pleural mesothelioma as indicated by the incidence of grade 3 or greater pneumonitis. [ Time Frame: conclusion of study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the response rate, progression free and overall survival rates of patients with malignant pleural mesothelioma treated with chemotherapy, with or without P/D, followed by IMRT to the pleura. [ Time Frame: conclusion of study ] [ Designated as safety issue: No ]
  • To determine the relationship between response to treatment and the levels of soluble mesothelin-related peptide (SMRP) and osteopontin. [ Time Frame: conclusion of study ] [ Designated as safety issue: No ]
  • To determine the pattern of progression: local recurrence versus metastatic disease. [ Time Frame: conclusion of study ] [ Designated as safety issue: No ]
  • To determine the incidence of any grade 3 or greater toxicity. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    This study will utilize the Common Terminology Criteria (CTC) version 4.0 for toxicity and Adverse Event reporting.


Estimated Enrollment: 40
Study Start Date: July 2008
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
This is a multicenter institution phase II toxicity study of chemotherapy +/- Pleurectomy/Decortication (P/D) followed by Intensity Modulated Radiation Therapy (IMRT) to the pleura in patients with malignant pleural mesothelioma. Patients will receive up to four cycles of pemetrexed (500mg/m2) and cisplatin (75mg/m2 ) or carboplatin (AUC=5) every 3 weeks. After completion of the chemotherapy, patients who are potential candidates for pleurectomy/decortication (P/D) at the time of enrollment will have this performed and within eight weeks from surgery they will be treated with IMRT, 50.4 Gy in 28 fractions. If patients have unresectable disease, they will be treated with IMRT, 50.4 Gy in 28 fractions after completion of the chemotherapy.
Other: Pemetrexed + Cisplatin or Carboplatin AUC=5 Pleurectomy/decortication (if feasible) Intensity Modulated Radiation Therapy
Patients who are potential candidates for pleurectomy/decortication (P/D) at the time of enrollment will receive up to four cycles of pemetrexed (500mg/m2) and cisplatin (75mg/m2) or carboplatin (AUC=5) every 3 weeks. Four to six weeks later chemotherapy, P/D will be attempted and within 8 weeks they will start treatment they will be treated with IMRT, 50.4 Gy in 28 fractions.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have a pathologically confirmed diagnosis either at MSKCC or at the participating site of malignant pleural mesothelioma.
  • No evidence of metastatic disease.
  • No prior chemotherapy for mesothelioma.
  • No prior radiation therapy except for localized prostate or pelvic radiation
  • Patient age ≥ or = to 18 years on day of signing informed consent.
  • Karnofsky performance status ≥ or = to 70%
  • Patients must have the ability to take folic acid, Vitamin B12, and dexamethasone according to protocol.
  • Patient must have the ability to interrupt NSAIDS 2 days before (5 days for longacting NSAIDs), the day of, and 2 days following administration of pemetrexed.
  • Pulmonary Function Tests:
  • FEV1 ≥ 30% of predicted postoperative (ppoFEV1) (as if the patient underwent a pneumonectomy) based on the following formula using the quantitative V/Q scan:
  • Predicted post-resection FEV1 = FEV1 x % perfusion to uninvolved lung from the quantitative V/Q scan report.
  • DLCO > 35% predicted
  • Patient must have adequate organ function as indicated by the following laboratory values:
  • Hematological:
  • Absolute neutrophil count ≥ or = to 1,500 /mcL
  • Platelets ≥ or = to 100,000 / mcL
  • Renal Calculated creatinine clearance (CrCl) ≥ or = to 45 mL/min (Creatinine clearance must be calculated using Cockcroft & Gault method) In cases of concern about renal toxicity from IMRT, an optional nuclear medicine kidney function scan may be performed prior to radiation therapy to determine the functional contribution of each kidney.
  • Hepatic
  • Serum total bilirubin ≤ or = to 1.5 X upper limit of normal (ULN) AST (SGOT) or ALT (SGPT) ≤ or = to 3.0 X ULN

Exclusion Criteria:

  • Pregnant or lactating women, or men or women not using effective contraception.
  • Patients with resectable disease for whom extrapleural pneumonectomy is necessary.
  • Patients with an active infection that require systemic antibiotics, antiviral, or antifungal treatments.
  • Patients with a concurrent active malignancy.
  • Patients with serious unstable medical illness.
  • Presence of third space fluid that cannot be controlled by drainage. For patients who develop or have baseline clinically significant pleural effusions before or during initiation of pemetrexed therapy consideration should be given to draining the effusion prior to dosing.
  • No acute congestive heart failure
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00715611

Contacts
Contact: Lee Krug, MD 646-888-4201
Contact: Andreas Rimner, MD 212-639-6025

Locations
United States, New Jersey
Memorial Sloan-Kettering at Basking Ridge Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Lee Krug, MD    646-888-4201      
Contact: Andreas Rimner, MD    212-639-6025      
United States, New York
Memorial Sloan-Kettering Cancer Center @ Suffolk Recruiting
Commack, New York, United States, 11725
Contact: Lee Krug, MD    646-888-4201      
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Lee Krug, MD    646-888-4201      
Contact: Andreas Rimner, MD    212-639-6025      
Principal Investigator: Lee Krug, MD         
Memorial Sloan-Kettering at Mercy Medical Center Recruiting
Rockville Centre, New York, United States
Contact: Lee Krug, MD    646-888-4201      
Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center Recruiting
Sleepy Hollow, New York, United States, 10591
Contact: Lee Krug, MD    212-639-8420      
United States, Texas
Md Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Daniel Gomez, MD         
Principal Investigator: Daniel Gomez, MD         
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Eli Lilly and Company
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Lee Krug, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00715611     History of Changes
Other Study ID Numbers: 08-053
Study First Received: July 11, 2008
Last Updated: February 10, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
pemetrexed
cisplatin
IMRT
PLEURA
Malignant
08-053

Additional relevant MeSH terms:
Mesothelioma
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial
Pemetrexed
Cisplatin
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on April 15, 2014