http://www.cancer.gov/search/ViewClinicalTrials.aspx?
cdrid=339681&version=patient&protocolsearchid=1027217

Purpose:  Drugs used in chemotherapy, such as cisplatin, use different ways to stop tumor cells from dividing so they stop growing or die. Pemetrexed disodium may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Giving pemetrexed disodium and cisplatin before surgery may shrink the tumor so that it can be removed during surgery. Giving radiation therapy after surgery may kill any remaining tumor cells.

Phase II trial to study the effectiveness of neoadjuvant pemetrexed disodium and cisplatin followed by extrapleural pneumonectomy and radiation therapy in treating patients who have stage I, stage II, or stage III pleural mesothelioma.

OBJECTIVES:

Primary

• Determine the feasibility of neoadjuvant chemotherapy comprising pemetrexed disodium and cisplatin followed by extrapleural pneumonectomy and high-dose postoperative 3D-conformal radiotherapy, in terms of 90-day progression-free survival, in patients with malignant pleural mesothelioma.

Secondary

• Determine the toxicity of this regimen in these patients.

• Determine progression-free survival and overall survival of patients treated with this regimen.

OUTLINE: This is a non-randomized, multicenter study.

• Neoadjuvant chemotherapy: Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1. Treatment repeats every 3 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients are evaluated 3 weeks after completion of neoadjuvant chemotherapy. Patients without disease progression proceed to surgery.

• Extrapleural pneumonectomy: Within 21-56 days after completion of neoadjuvant chemotherapy, patients undergo extrapleural pneumonectomy. Patients are evaluated 30 days after surgery. Patients without disease progression undergo high-dose 3D-conformal radiotherapy.

• High-dose 3D-conformal radiotherapy: Beginning 30-84 days after surgery, patients undergo high-dose 3D-conformal radiotherapy daily for 30 days.

After completion of study treatment, patients are followed on days 42 and 90, every 3 months for 1 year, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 52 patients will be accrued for this study.

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant pleural mesothelioma

• All subtypes allowed

• T1-3, N0-1, M0 disease

• No N2 or N3 involvement confirmed by mediastinoscopy within 21 days before study entry

• No clinical invasion of mediastinal structures (e.g., heart, aorta, spine, esophagus)

• No wide-spread chest wall invasion except focal chest wall lesions

• No clinical or radiological evidence of shrinking hemithorax

• No clinically significant third-space fluid (e.g., pleural effusions or ascites) that cannot be managed with thoracentesis or pleurodesis

PATIENT CHARACTERISTICS:

Age 

• Under 70

Performance status

• WHO 0-1

Life expectancy

• Not specified

Hematopoietic

• WBC > 3,500/mm^3

• Absolute neutrophil count > 1,500/mm^3

• Platelet count > 100,000/mm^3

• Hemoglobin ≥ 11 g/dL

Hepatic

• AST and ALT < 1.5 times upper limit of normal (ULN)

• Bilirubin < 1.5 times ULN

• Alkaline phosphatase < 1.5 times ULN

Renal

• Creatinine clearance ≥ 60 mL/min

• Acceptable (predicted) post-radiotherapy renal function by semiquantitative isotope renography, with a relative contribution of the contralateral kidney of ≥ 40%

Pulmonary

• See Disease Characteristics

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 3 months after completion of study treatment

• Deemed to be fit enough to undergo study treatment

• No preexisting sensory neurotoxicity > grade 1

• No uncontrolled infection

• No prior or concurrent melanoma, breast cancer, or hypernephroma

• No other malignancy within the past 5 years except carcinoma in situ of the cervix or adequately treated basal cell skin cancer

• No psychological, familial, sociological, or geographical condition that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent immunotherapy

• No concurrent routine use of colony-stimulating factors during neoadjuvant chemotherapy

• Concurrent secondary prophylactic use allowed during neoadjuvant chemotherapy

• No concurrent secondary prophylactic use of colony-stimulating factors during post-operative radiotherapy

 Chemotherapy

• No prior chemotherapy for mesothelioma

Endocrine therapy

• No concurrent hormonal cancer therapy

Radiotherapy

• No prior radiotherapy to the lower neck, thorax, or upper abdomen

Surgery

• See Disease Characteristics

Other

• No other concurrent anticancer therapy

• No other concurrent experimental medications

• No nonsteroidal anti-inflammatory drugs or salicylates for 2 days before, during, and 2 days after administration of neoadjuvant chemotherapy (5 days before and 2 days after for drugs with a long half-life [e.g., naproxen, piroxicam, diflunisal, or nabumetone])

Treatment/Intervention:

Patients will receive an infusion of pemetrexed disodium and a 1-hour infusion of cisplatin every 3 weeks for up to four courses. Within 3-8 weeks after completing chemotherapy, patients will undergo surgery. Beginning 4-8 weeks after surgery, they will undergo radiation therapy to the chest 5 days a week for up to 6 weeks. Patients will be evaluated every 3 months for 2 years.

Important:

If you are interested in participating in a clinical trial, contact your doctor for a referral or call a trial contact person listed below. If you have questions about cancer or clinical trials, call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237). General information about clinical trials, including risks, benefits, and costs, can be found on NCI's Web site.

Trial Sites and Contacts

Please refer to this study by ClinicalTrials.gov identifier  NCT00227630

Belgium
      Universitair Ziekenhuis Antwerpen, Edegem,  B-2650,  Belgium; Recruiting

Paul Van Schil, MD  32-30-821-37-69    paul.van.schil@uza.be 

Study chairs or principal investigators

Paul Van Schil, MD,  Study Chair,  Universitair Ziekenhuis Antwerpen   

*** POSTED OCTOBER  2003 ***
*** RE-POSTED SEPTEMBER 2005 ***