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

NCT00715611 | Active Not Recruiting Phase 2

• 1 other identifier: 08-053
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 12

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

Keywords

pemetrexed; cisplatin; IMRT; PLEURA; Malignant; 08-053

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

1

EXPERIMENTAL

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.

Procedure: Pleurectomy/Decortication; Drug: pemetrexed and cisplatin or carboplatin; Radiation: Intensity Modulated Radiation Therapy

Interventions

Pleurectomy/Decortication PROCEDURE

Pleurectomy/decortication will be performed as per standard technique

Also known as: (P/D)

1

pemetrexed and cisplatin or carboplatin 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.

1

Intensity Modulated Radiation Therapy 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).

Also known as: IMRT

1

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• For all patients: DLCO \> 40% predicted (corrected for Hgb)
• 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:
• Absolute neutrophil count ≥1.5 K/mcL
• Platelets ≥100 K/mcL
• Serum total bilirubin ≤ 1.5 X ULN
• AST (SGOT) or ALT (SGPT) ≤ 3.0 X ULN Note: patients enrolled after chemotherapy do not have to meet the above criteria

You may not qualify if:

• \> 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• M.D. Anderson Cancer Center: collaborator
• Princess Margaret Hospital, Canada: collaborator
• Mayo Clinic: collaborator
• Brigham and Women's Hospital: collaborator

Study Sites (12)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

Memorial Sloan Kettering at Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Cancer Center @ Suffolk-Commack

Commack, New York, 11725, United States

Location

Memoral Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering at Rockville Center, NY

Rockville Centre, New York, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Md Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 27325859 DERIVED

Related Links

• Memorial Sloan-Kettering Cancer Center

MeSH Terms

Conditions

Mesothelioma

Interventions

Cerebral Decortication; Pemetrexed; Cisplatin; Carboplatin; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Neurosurgical Procedures; Surgical Procedures, Operative; 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; Coordination Complexes; Organic Chemicals; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• Charles Simone, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2008
• First Posted: July 15, 2008
• Study Start: October 11, 2008
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: August 15, 2025

Record last verified: 2025-08

Locations

US (12)