Mesothelioma Newsletter - Clinical Trial: Neoadjuvant Pemetrexed Disodium and Cisplatin Followed by Surgery and Radiation Therapy in Treating Patients With Pleural Mesothelioma

RATIONALE: 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.

PURPOSE: 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.

Condition	Intervention	Phase
Localized Malignant Mesothelioma	Drug: cisplatin Drug: pemetrexed disodium Procedure: chemotherapy Procedure: conventional surgery Procedure: enzyme inhibitor therapy Procedure: neoadjuvant therapy Procedure: radiation therapy Procedure: surgery	Phase II

MedlinePlus related topics: Cancer; Cancer Alternative Therapies; Mesothelioma
Genetics Home Reference related topics: Cancer

Study Type: Interventional
Study Design: Treatment

Official Title: Phase II Study of Neoadjuvant Pemetrexed Disodium and Cisplatin Followed By Extrapleural Pneumonectomy and Radiotherapy in Patients With Stage I, II, or III Pleural Mesothelioma

Further study details as provided by National Cancer Institute (NCI):

OBJECTIVES:

Primary

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

Determine the 1- and 2-year disease-free and median survival of patients treated with this regimen
.
Determine the clinical response rate by radiological assessment in patients treated with this regimen.
Determine the quantitative and qualitative toxic effects of this regimen in these patients.
Determine the pattern of relapse (local vs metastatic) in patients treated with this regimen.
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.
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.

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.

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

Eligibility

Ages Eligible for Study: 18 Years and above, Genders Eligible for Study: Both

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed pleural mesothelioma
Stage I, II, or III (T1-3, N0-2, M0)
No cardiac involvement

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/mm^3
Platelet count at least 100,000/mm^3
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

FEV_1 at least 2 L OR at least 35% of predicted postoperative (ppoFEV_1)
DLCO greater than 35% of ppoFEV_1
PCO_2 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

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

Location and Contact Information

Please refer to this study by ClinicalTrials.gov identifier NCT00072397

Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston, Massachusetts, 02115, United States; Recruiting
Clinical Trials Office - Dana-Farber/Harvard Cancer Center 617-582-8480

New York
Memorial Sloan-Kettering Cancer Center, New York, New York, 10021, United States; Recruiting

Clinical Trials Office - Memorial Sloan-Kettering Cancer Cente 646-227-2149

Study chairs or principal investigators

Lee M. Krug, MD, Principal Investigator, Memorial Sloan-Kettering Cancer Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database

Study ID Numbers: CDR0000339681; MSKCC-03078; LILLY-H3E-US-JMGA
Last Updated: May 10, 2006
Record first received: November 4, 2003
ClinicalTrials.gov Identifier: NCT00072397
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2006-05-18

Source: www.clinicaltrials.gov