A Multicenter Phase II Trial of Neo-Adjuvant Pemetrexed (ALIMTA) Plus Cisplatin Followed by Surgery and Radiation for Pleural Mesothelioma
18 Years
N/A
Both
Malignant Mesothelioma
Trial Information
A Multicenter Phase II Trial of Neo-Adjuvant Pemetrexed (ALIMTA) Plus Cisplatin Followed by Surgery and Radiation for Pleural Mesothelioma
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Pathological complete response rate
Safety Issue:
No
Principal Investigator
Lee M. Krug, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Memorial Sloan-Kettering Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000339681
NCT ID:
NCT00072397
Start Date:
July 2003
Completion Date:
Related Keywords:
- Malignant Mesothelioma
- localized malignant mesothelioma
- Mesothelioma
Name | Location |
|---|---|
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
| Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute | Boston, Massachusetts 02115 |
