Surgery With or Without Intraoperative Heated Cisplatin and Sodium Thiosulfate Followed by Pemetrexed Disodium and Cisplatin in Treating Patients With Malignant Pleural Mesothelioma

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Basic Trial Information

PhaseTypeAgeTrial IDs
Phase IITreatment18 and over04-063
NCI-2010-00088, NCT00165503

Trial Description


RATIONALE: Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of cancer, either by killing the cancer cells or by stopping them from dividing. Heating a chemotherapy solution and infusing it directly into the abdomen may kill more tumor cells. Chemoprotective drugs, such as sodium thiosulfate, may protect normal cells from the side effects of chemotherapy. Pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy, given before and after surgery, followed by pemetrexed disodium may be effective treatment for malignant pleural mesothelioma.

PURPOSE: This randomized phase II trial is studying how well surgery with or without intraoperative heated cisplatin and sodium thiosulfate followed by pemetrexed disodium and cisplatin works in treating patients with malignant pleural mesothelioma.

Further Study Information


I. To determine the feasibility of administering adjuvant cisplatin plus ALIMTA to patients undergoing P/D with intraoperative intracavitary hyperthermic cisplatin at a dose of 175 mg/m2 and sodium thiosulfate.

II. To prospectively determine the morbidity and mortality of this treatment protocol.

III. To prospectively determine time to tumor recurrence and patient survival.


Patients are randomized to 1 of 2 treatment arms.

All patients undergo surgical cytoreduction by pleurectomy/decortication.

Arm I: Patients undergo intraoperative hyperthermic lavage with cisplatin over 1 hour followed immediately by sodium thiosulfate IV continuously over 12 hours. Beginning 6-10 weeks after surgery, patients receive pemetrexed disodium IV and cisplatin IV on day 1. Treatment with pemetrexed disodium and cisplatin repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.

Arm II: Beginning 6-10 weeks after surgery, patients receive pemetrexed disodium and cisplatin as in arm I.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 2 years, and then once annually thereafter

Eligibility Criteria

Inclusion Criteria:

Pre-operative hemoglobin > 9 mg/dl

Patient available for follow-up in Boston at Brigham & Women's Hospital and Dana-Farber Cancer Institute

Prior to initiation of adjuvant therapy:

Ejection fraction > 45%

Serum creatinine =< 1.3 mg/dL upper limit of normal (ULN)

Platelet count of >= 100 x 10^9/L

Enrollment and dosing decisions based on creatinine clearance will be made using local lab values (calculated using the standard Cockroft and Gault formula)

Serum creatinine =< 1.5 mg/dL

Patients with histopathologic confirmation of malignant pleural mesothelioma by a Brigham and Women's Hospital staff pathologist

Patients who are able to tolerate surgical cytoreduction

The patient has signed an Institutional Review Board approved consent form, which conforms to federal and institutional guidelines

Male or non-pregnant female (confirmatory pregnancy test within 2 weeks of surgery for premenopausal women)

Male and female patients must agree to use a reliable method of birth control during and for 3 months following the last dose of study drug

No evidence of spread outside the ipsilateral hemithorax by chest CT and chest MRI, obtained within 8 weeks prior to surgery

Assessment of cardiac function by EKG and echocardiogram; Grossly normal cardiac function with an EKG showing no cardiomyopathy or acute changes and with a cardiologist risk assessment for patients over the age of 40 within 8 weeks prior to registration

Pre-operative WBC > 4 K/uL (with an absolute neutrophil count (ANC) >= 1.5 x 10^9/L)

Pre-operative platelet count of > 100 K/mm^3

Patients can receive transfusions of PRBC and platelets to attain the above levels

Estimated life expectancy of at least 12 weeks

Evidence of adequate renal and hepatic function:

Liver function tests (LFT): SGOT (AST) of < 80 IU/L and

total bilirubin of < 1.9 mg/dL

Grossly normal contralateral pulmonary function with a chest radiograph and chest CT scan that do not show acute infiltrates

Karnofsky performance status of 70% or greater

No evidence of disease progression by chest CT or chest MRI, obtained at 8 weeks following P/D

Adequate organ function including the following prior to initiation of adjuvant therapy:

Adequate bone marrow reserve:

Absolute neutrophil count (ANC) >= 1. 5 x 10^9/L)

Hemoglobin > 9 g/dL

Patients can receive transfusions of PRBC and platelets to attain these levels

Hepatic: bilirubin =< 1.5 times the upper limit of normal (ULN)

Alkaline phosphatase =< 3.0 x ULN

Aspartate transaminase =< 3.0 x ULN

Alanine transaminase =< 3.0 x ULN

Renal: calculated creatinine clearance (CrCl) >= 45 mL/min based on Cockroft and Gault formula or on measure glomerular filtration rate (GFR) using the appropriate radiolabeled method (51-CrEDTA or Tc99m-DTPA)

SGOT (AST) of < 80 IU/L

Total bilirubin of < 1.9 mg/dL

Cardiac: an echocardiogram at 6 weeks showing the following:

No severe valvular abnormalities

No pulmonary hypertension (systolic pulmonary artery pressure > 45mm Hg)

No pericardial effusion

No constrictive physiology

Karnofsky performance status of 70% or greater

Estimated life expectancy of at least 12 weeks

Exclusion Criteria:

Liver disease

Extended disease outside the ipsilateral hemithorax as determined on pre-operative radiographs or intraoperative findings

Positive extrapleural nodes as determined by mediastinoscopy

Evidence of distant metastatic disease

Patients having severe non-malignant co-morbid disease:

Uncontrolled angina (NYHA class III or IV)

Myocardial infarction in the past 6 months

Renal insufficiency (creatinine > 1.5)

Pulmonary hypertension (systolic pulmonary artery pressure > 45 mmHg)

Patients who are pregnant or breast feeding

Serious concomitant systemic disorders (eg, active infection) that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study

Presence of active concomitant malignancy; patients with prior malignancy who have been adequately treated and are in remission for over 3 years are eligible

Karnofsky performance status of less than 70%

Patients with psychiatric or addictive disorders, which would preclude informed consent

Any previous chemotherapy or radiation therapy administered to treat mesothelioma

Chemotherapy or radiation therapy administered within 3 years for another malignancy

Patients with large tumor burden (> 1000 cc^3) or decreased lung volume (< 25%) of the affected hemithorax due to tumor growth as demonstrated on chest imaging (CT scan, MRI, chest x-ray)

Patients who have, at any time prior to surgery, a platelet count higher than 450 K/mm^3

Prior to initiation of adjuvant therapy:

Gross disease (estimated thickness > 10 mm at any intrathoracic location) present within the hemithorax after P/D

Evidence of disease progression on Chest CT or Chest MRI in the ipsilateral hemithorax at 6-10 weeks following P/D

Evidence of distant metastatic disease

Inability to interrupt aspirin or other nonsteroidal anti-inflammatory agents for a 5- day period (8-day period for long-acting agents such as piroxicam)

Inability or unwillingness to take folic acid, vitamin B12 supplementation, or dexamethasone

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

Dana-Farber Harvard Cancer Center

  • National Cancer Institute
David J. Sugarbaker, Principal Investigator

Trial Sites



Brigham and Women's Hospital

David J. Sugarbaker
Ph: 617-732-5004

David J. Sugarbaker
Principal Investigator

Dana-Farber Cancer Institute

David J. Sugarbaker
Ph: 617-732-5004

David J. Sugarbaker
Principal Investigator

Link to the current record.
NLM Identifer NCT00165503

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