Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Neoadjuvant Pemetrexed Disodium and Cisplatin Followed by Surgery and Radiation Therapy in Treating Patients With Pleural Mesothelioma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	18 and over	NCI, Pharmaceutical / Industry	MSKCC-03078 LILLY-H3E-US-JMGA, NCT00072397

Objectives

Primary

1. Determine the pathological complete response rate in patients with stage I, II, or III pleural mesothelioma treated with neoadjuvant pemetrexed disodium and cisplatin followed by extrapleural pneumonectomy and radiotherapy.

Secondary

1. Determine the 1- and 2-year disease-free and median survival of patients treated with this regimen.
2. Determine the clinical response rate by radiological assessment in patients treated with this regimen.
3. Determine the quantitative and qualitative toxic effects of this regimen in these patients.
4. Determine the pattern of relapse (local vs metastatic) in patients treated with this regimen.
5. Determine the time to event efficacy variables (i.e., time to objective tumor response, time to treatment failure, time to progressive disease, and overall survival) in patients treated with this regimen.
6. Correlate response to treatment with this regimen with levels of TS, DHFR, GARFT, FPGS, DPD, RFCI, alpha-FR, and ERCC1 in the mesothelioma tissue of these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed pleural mesothelioma
  • Stage I, II, or III (T1-3, N0-2, M0)



• No cardiac involvement

Prior/Concurrent Therapy:

Biologic therapy

• No prior immunotherapy or biologic therapy
• No prior intracavity immunomodulators (chemical pleurodesis allowed)
• No concurrent immunotherapy or biologic therapy
• No concurrent routine filgrastim (G-CSF)
• No concurrent stimulator of thrombopoiesis

Chemotherapy

• No prior systemic chemotherapy
• No other concurrent chemotherapy

Endocrine therapy

• No concurrent anticancer hormonal therapy

Radiotherapy

• No prior radiotherapy
• No concurrent radiotherapy

Surgery

• No prior surgical resection of mesothelioma
  • Prior chemical pleurodesis allowed
• No concurrent anticancer surgery

Other

• More than 30 days since prior drug not approved for any indication
• No prior intracavity cytotoxic drugs (chemical pleurodesis allowed)
• No prior participation in this study or any other study investigating pemetrexed disodium
• No other concurrent experimental medication (thymidine allowed)
• No other concurrent anticancer therapy
• No nonsteroidal anti-inflammatory drugs (NSAIDs) or salicylates 2 days before, the day of, or 2 days after study therapy
  • No NSAIDs or salicylates with a long half-life (e.g., piroxicam or nabumetone) 5 days before, the day of, or 2 days after study therapy

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³
• Hemoglobin at least 9 g/dL

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 3.0 times ULN
• AST and ALT no greater than 3.0 times ULN

Renal

• Creatinine clearance at least 45 mL/min

Cardiovascular

• See Disease Characteristics
• Cardiac function adequate by radionuclide stress test, exercise stress test to maximal exercise level, or stress echocardiogram

Pulmonary

• FEV₁ at least 2 L OR at least 35% of predicted postoperative (ppoFEV₁)
• DLCO greater than 35% of ppoFEV₁
• PCO₂ less than 50 on ABG

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study participation
• Able and willing to take folic acid, cyanocobalamin, or dexamethasone
• Willing to have cytoreduction by extrapleural pneumonectomy
• No active infection
• Suitable candidate for this study therapy
• No concurrent serious systemic disorder (e.g., active infection) that would compromise the patient's safety or ability to complete the study
• No other primary malignancy except carcinoma in situ of the cervix, adequately treated nonmelanoma skin cancer, low-grade (Gleason score no greater than 6) localized adenocarcinoma of the prostate, or other malignancy curatively treated within the past 2 years with no evidence of recurrence

Expected Enrollment

A total of 77 patients will be accrued for this study.

Outcomes

Pathological complete response rate

Outline

This is an open-label, multicenter study.

• Preoperative chemotherapy: Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.



• Extrapleural pneumonectomy: Patients undergo extrapleural pneumonectomy within 3-8 weeks after the last course of chemotherapy.



• Hemi-thoracic radiotherapy: Beginning 4-8 weeks after surgery, patients undergo radiotherapy to the chest once daily 5 days a week for 6 weeks.

Patients are followed every 3 months for 2 years.

Krug LM, Pass HI, Rusch VW, et al.: Multicenter phase II trial of neoadjuvant pemetrexed plus cisplatin followed by extrapleural pneumonectomy and radiation for malignant pleural mesothelioma. J Clin Oncol 27 (18): 3007-13, 2009.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Lee Krug, MD, Principal investigator		Ph: 212-639-8420; 800-525-2225

Registry Information
Official Title		A Multicenter Phase II Trial of Neo-Adjuvant Pemetrexed (ALIMTA) Plus Cisplatin Followed by Surgery and Radiation for Pleural Mesothelioma
Trial Start Date		2003-07-22
Registered in ClinicalTrials.gov		NCT00072397
Date Submitted to PDQ		2003-09-30
Information Last Verified		2006-08-15
NCI Grant/Contract Number		CA08748

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