Pleurectomy/Decortication (Neo) Adjuvant Chemotherapy and Intensity Modulated Radiation Therapy to the Pleura in Patients With Locally Advanced Malignant Pleural Mesothelioma

Mesothelioma Clinical Trial

Official title:

Phase II Toxicity Study of Pleurectomy/Decortication, (Neo) Adjuvant Chemotherapy and Intensity Modulated Radiation Therapy to the Pleura in Patients With Locally Advanced Malignant Pleural Mesothelioma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00715611
• Other study ID #: 08-053
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 11, 2008
• Est. completion date: July 2025

Study information

• Verified date: May 2024
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 implementation of standard pleurectomy/decortication (removal of the surface lining of the lung) and standard chemotherapy followed by IMRT performed at other centers. Patients will undergo pleurectomy/decortication chemotherapy and hemithoracic pleural IMRT to the pleura in patients with malignant pleural mesothelioma.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 65
• Est. completion date: July 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Provide written informed consent to participate on the study
• Patients must have a pathologically confirmed diagnosis either at MSKCC or at the participating site of stage I-III malignant pleural mesothelioma
• Epithelioid or biphasic histology subtype (Note: patients with biphasic histology can have < 10% sarcomatoid)
• No evidence of metastatic disease.
• Patient age = 18 years but = 80 years at the time of consent.
• Karnofsky performance status = 80%
• Pulmonary Function Tests:

1. For all patients: DLCO > 40% predicted (corrected for Hgb)

2. For patients enrolled post-P/D, only: FEV1 >/= 35% (corrected for Hgb) (Note:

patients enrolled prior to P/D will have PFTs repeated pre-IMRT. If this criteria is not met, they will be removed from study)

• In cases of concern about decreased renal function and potential high radiation dose to the kidneys, an optional nuclear medicine kidney function scan may be performed prior to radiation therapy to determine the functional contribution of each kidney.
• Patient enrolled prior to chemotherapy must have adequate organ function as indicated

by the following laboratory values:

1. Absolute neutrophil count =1.5 K/mcL

2. Platelets =100 K/mcL

3. Serum total bilirubin = 1.5 X ULN

4. AST (SGOT) or ALT (SGPT) = 3.0 X ULN Note: patients enrolled after chemotherapy do not have to meet the above criteria

Exclusion Criteria:

• > 10% Sarcomatoid or desmoplastic histology
• Continuous oxygen use
• Prior nephrectomy on the contralateral side of MPM
• Prior intrapleural therapy (except pleurodesis) or intrapleural therapy at the time of P/D (i.e.: intrapleural chemotherapy, photodynamic therapy, intrapleural betadine)
• Prior thoracic radiation therapy preventing hemithoracic pleural IMRT
• Bulky disease in the fissure preventing lung-sparing pleural IMRT
• Patients undergoing extrapleural pneumonectomy
• Patients with an active infection that require systemic antibiotics, antiviral, or antifungal treatments
• Patients with a concurrent active malignancy (except squamous or basal cell carcinoma of the skin)
• 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 drain the effusion prior to chemotherapy administration
• No acute congestive heart failure
• Pregnant or lactating women
• Men or women not using effective contraception Reproductive risks Patients should not become pregnant or father a baby while on this study because the drugs in this study can affect an unborn baby. Women should not breast-feed a baby while on this study. Women of childbearing age will be counseled to use birth control while on this study.

Related Conditions & MeSH terms

• Mesothelioma
• Mesothelioma, Malignant

Intervention

Procedure:
• Pleurectomy/Decortication
Pleurectomy/decortication will be performed as per standard technique

Drug:
• pemetrexed and cisplatin or carboplatin
The combination of pemetrexed and cisplatin or carboplatin will be given every 3 weeks for up to 4 cycles. Pemetrexed will be administered at 500mg/m2 as a 10-minute infusion. Cisplatin will be administered at 75mg/m2 as a 60-minute infusion. Carboplatin will be administered at an AUC of 5 over 30 minutes. Chemotherapy may be administered in the neoadjuvant or adjuvant setting.

Radiation:
• Intensity Modulated Radiation Therapy
IMRT will be administered over approximately 6 weeks at 50.4 Gy in 28 fractions with an optional SIB to gross residual disease (pending meeting normal tissue constraints).

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering at Basking Ridge	Basking Ridge	New Jersey
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Memorial Sloan Kettering Cancer Center @ Suffolk-Commack	Commack	New York
United States	Memoral Sloan Kettering Westchester	Harrison	New York
United States	Md Anderson Cancer Center	Houston	Texas
United States	Memorial Sloan Kettering Monmouth	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Memorial Sloan Kettering at Rockville Center, NY	Rockville Centre	New York
United States	Moffitt Cancer Center	Tampa	Florida
United States	Memorial Sloan Kettering Nassau	Uniondale	New York

Sponsors (5)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	Brigham and Women's Hospital, M.D. Anderson Cancer Center, Mayo Clinic, Princess Margaret Hospital, Canada

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	number of patients = grade 3 pneumonitis	Grade 3 pneumonitis is defined as symptomatic, interfering with ADL's and requiring oxygen support as defined by the NCI Common Terminology Criteria (CTC) version 4.0 for toxicity and Adverse Event reporting.	2 years

External Links

•   Memorial Sloan-Kettering Cancer Center