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

NCT ID: NCT00715611

Last Updated: 2025-08-15

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-11
• Study Completion Date: 2026-07-31

Brief 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.

Conditions

Mesothelioma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

This is a multicenter phase II toxicity study of pleurectomy/decortication (P/D) followed by adjuvant chemotherapy and Intensity Modulated Radiation Therapy (IMRT) to the pleura in patients with malignant pleural mesothelioma. Alternatively, chemotherapy may be administered in the neoadjuvant setting prior to P/D, followed by IMRT. Patients deemed resectable at the time of enrollment will undergo P/D with the goal of a macroscopic complete resection (MCR). Those with disease progression or severe toxicity will stop chemotherapy and undergo a PET scan.

Group Type: EXPERIMENTAL

Pleurectomy/Decortication

Intervention Type: PROCEDURE

Pleurectomy/decortication will be performed as per standard technique

pemetrexed and cisplatin or carboplatin

Intervention Type: DRUG

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.

Intensity Modulated Radiation Therapy

Intervention Type: RADIATION

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).

Interventions

Pleurectomy/Decortication

Pleurectomy/decortication will be performed as per standard technique

Intervention Type: PROCEDURE

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.

Intervention Type: DRUG

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).

Intervention Type: RADIATION

Other Intervention Names

(P/D); IMRT

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

M.D. Anderson Cancer Center

OTHER

Sponsor Role: collaborator

Princess Margaret Hospital, Canada

OTHER

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Charles Simone, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Moffitt Cancer Center

Tampa, Florida, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Memorial Sloan Kettering at Basking Ridge

Basking Ridge, New Jersey, 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 @ Suffolk-Commack

Commack, New York, United States

Memoral Sloan Kettering Westchester

Harrison, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Memorial Sloan Kettering at Rockville Center, NY

Rockville Centre, New York, United States

Memorial Sloan Kettering Nassau

Uniondale, New York, United States

Md Anderson Cancer Center

Houston, Texas, United States

Countries

United States

References

Rimner A, Zauderer MG, Gomez DR, Adusumilli PS, Parhar PK, Wu AJ, Woo KM, Shen R, Ginsberg MS, Yorke ED, Rice DC, Tsao AS, Rosenzweig KE, Rusch VW, Krug LM. Phase II Study of Hemithoracic Intensity-Modulated Pleural Radiation Therapy (IMPRINT) As Part of Lung-Sparing Multimodality Therapy in Patients With Malignant Pleural Mesothelioma. J Clin Oncol. 2016 Aug 10;34(23):2761-8. doi: 10.1200/JCO.2016.67.2675. Epub 2016 Jun 20.

Reference Type: DERIVED

PMID: 27325859 (View on PubMed)

Related Links

http://www.mskcc.org

Memorial Sloan-Kettering Cancer Center

Other Identifiers

08-053

Identifier Type: -

Identifier Source: org_study_id