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

• ClinicalTrials.gov Identifier: NCT00715611
• Recruitment Status: Active, not recruiting
• First Posted: July 15, 2008
• Last Update Posted: May 10, 2023
• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: M.D. Anderson Cancer Center; Princess Margaret Hospital, Canada; Mayo Clinic; Brigham and Women's Hospital
• Information provided by (Responsible Party): Memorial Sloan Kettering Cancer Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Mesothelioma	Procedure: Pleurectomy/Decortication; Drug: pemetrexed and cisplatin or carboplatin; Radiation: Intensity Modulated Radiation Therapy	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 65 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Study Start Date: October 11, 2008
• Estimated Primary Completion Date: July 2023
• Estimated Study Completion Date: July 2023

Arms and Interventions

Arm

Intervention/treatment

Experimental: 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.

Procedure: Pleurectomy/Decortication; Pleurectomy/decortication will be performed as per standard technique; Other Name: (P/D); 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).; Other Name: IMRT

Outcome Measures

Primary Outcome Measures :

1. number of patients ≥ grade 3 pneumonitis [ Time Frame: 2 years ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Florida

Moffitt Cancer Center

Tampa, Florida, United States, 33612

United States, Massachusetts

Brigham and Women's Hospital

Boston, Massachusetts, United States, 02115

United States, Minnesota

Mayo Clinic Cancer Center

Rochester, Minnesota, United States, 55905

United States, New Jersey

Memorial Sloan Kettering at Basking Ridge

Basking Ridge, New Jersey, United States, 07920

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, United States, 07748

Memorial Sloan Kettering Bergen

Montvale, New Jersey, United States, 07645

United States, New York

Memorial Sloan Kettering Cancer Center @ Suffolk

Commack, New York, United States, 11725

Memorial Sloan Kettering West Harrison

Harrison, New York, United States, 10604

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

Memorial Sloan Kettering at Mercy Medical Center

Rockville Centre, New York, United States

Memorial Sloan Kettering Cancer Center at Phelps Memorial Hospital Center

Sleepy Hollow, New York, United States, 10591

Memorial Sloan Kettering Nassau

Uniondale, New York, United States, 11553

United States, Texas

Md Anderson Cancer Center

Houston, Texas, United States, 77030

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center

M.D. Anderson Cancer Center

Princess Margaret Hospital, Canada

Mayo Clinic

Brigham and Women's Hospital

Investigators

• Principal Investigator: Andreas Rimner, MD; Memorial Sloan Kettering Cancer Center

More Information

Additional Information:

Memorial Sloan-Kettering Cancer Center 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00715611
• Other Study ID Numbers: 08-053
• First Posted: July 15, 2008
• Last Update Posted: May 10, 2023
• Last Verified: May 2023

Keywords provided by Memorial Sloan Kettering Cancer Center:

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

Additional relevant MeSH terms:

Mesothelioma; Mesothelioma, Malignant; 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; Carboplatin; Pemetrexed; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors