Trimodal Lung-Sparing Treatment of Pleural Mesothelioma

Phase II, A Study of Lung-Sparing Combined Modality Protocol for the Treatment for Malignant Pleural Mesothelioma: The Columbia Protocol

The primary objective of the study is to determine the feasibility (as determined by lack of serious adverse events) and tolerability (as determined by patient's ability to complete the study) of a multimodal lung sparing regimen of surgery, interpleural and intravenous chemotherapy, and local P-32 irradiation for malignant pleural mesothelioma.

Study Overview

• Status: Terminated
• Conditions: Pleural Mesothelioma
• Intervention / Treatment: Drug: Doxorubicin; Drug: Cisplatin; Drug: Pemetrexed; Radiation: Radiotherapy

Detailed Description

Current surgical and/or chemotherapeutic approaches for malignant pleural mesothelioma are unsatisfactory and have not been shown to significantly prolong survival, and often lead to worsened pulmonary function and quality of life. We will investigate whether a prospective trial of trimodal (surgery, pleural chemotherapy, and pleural radiation) therapy can improve the overall 1 year survival in patients with malignant pleural mesothelioma. The proposed treatment will include exploratory thoracoscopy, placement of Mediport catheters into the pleural space, intraoperative chemotherapy, repeated intraperitoneal chemotherapy, and intrapleural instillation of radioactive P32 to radiate the pleural surfaces. In addition, because this study is randomized, half the patients will receive an additional three intravenous systemic chemotherapy treatments of cisplatin and pemetrexed (Alimta) in tandem with their intrapleural chemotherapy (weeks 3, 6, and 9 only).

The potential significance of this research is that such treatment may render it less necessary to surgically remove the affected lungs in whole or in part, in order to achieve significant disease cytoreduction. We hope to alter the currently accepted paradigm that major lung surgery is an inescapable component of such treatment, and advance the concept that a combination of judicious preparative surgery, systemic chemotherapy, and locoregional drug treatment of the pleural surfaces may offer the best hope for prolongation of survival with intact lung function.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed malignant mesothelioma, < 20% sarcomatoid type
• No radiographic or other imaging evidence of Stage IV (cardiac, mediastinal, peritoneal, other distant) disease.
• Ineligible for other high priority national or institutional study.
• Age >18 years [to physiologic 75 years].
• Life expectancy > 3 months.
• Performance status, PS 0-2 [Karnofsky Performance Status, KPS=70-100 %].
• Prior therapy allowed (one prior systemic regimen) meeting the following parameters.
• No prior chest radiation therapy within 6 weeks of treatment
• No prior chemotherapy regimens within four weeks of treatment
• Non pregnant, non-lactating. (serum HCG test will be performed in patients in whom there is a possibility of pregnancy.)
• Required initial laboratory data/clinical parameters (see also Sec. 8.0) White cell count: >3000/ul. Platelet count: >100,000/ul. Creatinine clearance: ≥ 45 ml/min Bilirubin: < 2 x ULN SGOT or SGPT: < 2 x ULN
• Informed Consent: Each patient must be completely aware of the nature of his/her disease process and must willingly give consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts.
• No other coexistent malignancy. However, curatively treated or fully controlled solid tumors (other than mesothelioma) may be eligible if in the judgement of the PI, the benefit of treatment outweighs the risk.
• No serious medical or psychiatric illness preventing informed consent or intensive treatment (e.g., serious infection, congestive heart failure, angina pectoris, cardiac arrhythmia(s), or uncontrolled hypertension). HIV status or other severe illnesses will be assessed using medical records.

Exclusion Criteria:

• If any of the inclusion criteria was not met.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Multimodal lung sparing regimen; Intrapleural chemotherapy plus systemic chemotherapy: Thoracoscopy to implant two intrapleural catheters followed by intrapleural chemotherapy with doxorubicin and cisplatin (weeks 1, 2, 4, 5, 7, and 8). Systemic chemotherapy treatments with cisplatin and pemetrexed during weeks 3, 6, and 9. Intrapleural radiotherapy with P-32 will be given 3 weeks after last dose of chemotherapy and 11 to 12 weeks after initial thoracoscopy.

Drug: Doxorubicin; A medication used in cancer chemotherapy, derived by chemical semisynthesis from a bacterial species.; Other Names: Doxil; Drug: Cisplatin; Platinum-based antineoplastic; Other Names: Cisplatinum; Platinol; Drug: Pemetrexed; Folate Analog Metabolic Inhibitor; Other Names: Alimta; Radiation: Radiotherapy; Standard procedure given 3 weeks after last dose of chemotherapy; Other Names: Intrapleural radiotherapy with P-32

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Who Were Able to Complete Trimodal Therapy (Combination of Surgery, Intrapleural and Systemic Chemotherapy and P-32 Radiotherapy).	To determine the feasibility of multimodal lung sparing regimen. Intrapleural chemotherapy (12 weeks) will be administered within two weeks after surgery. Approximately 30 days post last dose of chemotherapy (+/- 14 days), the patient should be reassessed for resolution of any treatment-related toxicity which may have occurred during the course of study participation.	20 weeks

Collaborators and Investigators

• Sponsor: Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2008
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: March 9, 2009
• First Submitted That Met QC Criteria: March 10, 2009
• First Posted (Estimate): March 11, 2009

Study Record Updates

• Last Update Posted (Actual): August 25, 2020
• Last Update Submitted That Met QC Criteria: August 12, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Adenoma; Neoplasms, Mesothelial; Pleural Neoplasms; Mesothelioma; Mesothelioma, Malignant; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Folic Acid Antagonists; Cisplatin; Doxorubicin; Pemetrexed
• Other Study ID Numbers: AAAB9658

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED