Pemetrexed Plus Cisplatin Neoadjuvant Therapy Followed By Surgery and Radiation in Mesothelioma

• Event Free Survival Rates at One and Two Years [ Time Frame: date of first dose of study drug to first observation of disease progression, death from any cause, discontinuation of treatment (up to 2 years) ] [ Designated as safety issue: No ]
  A participant was defined event-free if they did not show a progressive disease (PD), did not die and did not discontinue the treatment early. Participants without assessment at 1-year (due to whatever reason) were considered as Not-Event-Free.
• Progression Free Survival (PFS) [ Time Frame: date of first dose of study drug to first date of disease progression or death from any cause (up to 44.6 months) ] [ Designated as safety issue: No ]
  Progression-free survival time is defined as the time from study enrollment to the first date of disease progression or death as a result of any cause. Progression-free survival time was censored at the date of the last follow-up visit for participants who were still alive and who had not progressed.
• Progression-Free Survival (PFS) Rates at One and Two Years [ Time Frame: Date of first dose of study drug to first date of disease progression or death from any cause, discontinuation of treatment (up to 2 years) ] [ Designated as safety issue: No ]
  Progression-free survival time is defined as the time from study enrollment to the first date of disease progression or death as a result of any cause. Progression-free survival time was censored at the date of the last follow-up visit for participants who were still alive and who had not progressed.
• Time to Progressive Disease [ Time Frame: Date of first dose of study drug to first observation of progressive disease (up to 44.6 months) ] [ Designated as safety issue: No ]
  Time to progressive disease was defined as the time from study enrollment to first date of disease progression. Time to progression was censored at the last date of follow-up visit for participants who were still alive and had not progressed. Time to progression was also censored at the date of death for participants whose death was not due to study disease.
• Overall Survival (OS) [ Time Frame: date of first dose of study drug to date of death from any cause (up to 52.8 months) ] [ Designated as safety issue: Yes ]
  Overall survival time was defined as the time from study enrollment to time of death as a result of any cause. Survival time was censored at the date of the last follow-up visit for participants who were still alive.
• Time to Tumor Response [ Time Frame: date of first dose of study drug to date of first observation of an objective tumor response (up to 23.6 months) ] [ Designated as safety issue: No ]
  Time to objective tumor response is defined as the time from study enrollment to the first observation of an objective tumor response. Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response (CR)=disappearance of all target lesions; Partial Response=30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD)=20% increase in sum of longest diameter of target lesions; Stable Disease (SD)=small changes that do not meet above criteria.
• Complete Pathological Response Rate [ Time Frame: date of first dose of study drug to date of surgery (up to 4.1 months) ] [ Designated as safety issue: No ]
  Resected tissue or pleural fluid are submitted to the pathologist as random specimens. The pathologist examines the specimens to determine whether or not micro residual disease is still present. If there is no evidence of micro-disease, pathologist can confirm "pathological complete response"
• Percent of Participants With a Tumor Response (Response Rate) [ Time Frame: Timeframe: date of first dose of study drug, end of cycle 3, to 30 days post study completion (up to 38.6 months) ] [ Designated as safety issue: No ]
  Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria define when cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progression") during treatments. Complete Response=disappearance of all target lesions; Partial Response=30% decrease in sum of longest diameter of target lesions; Progressive Disease=20% increase in sum of longest diameter of target lesions; Stable Disease=small changes that do not meet above criteria.
• Number of Participants With Adverse Events (Pharmacology Toxicity) [ Time Frame: baseline up to 676 days ] [ Designated as safety issue: Yes ]
  The list of serious adverse events and other non-serious adverse events are in the Reported Adverse Event section.

• -To determine the 1- and 2- year disease free survival, and median survival.
• -To determine complete pathological response rate
• -To determine clinical response rate measured by radiological assessment.
• -To characterize the quantitative and qualitative toxicities of chemotherapy, surgery and radiation in this patient population.
• -To determine the pattern of relapse (local versus metastatic).
• -To measure time-to-event efficacy variables including: time to objective tumor response for responding patients-time to progressive disease-overall survival

Phase II trial of Neoadjuvant Chemotherapy with Pemetrexed plus Cisplatin followed by Surgery and Radiotherapy in patients with Malignant Pleural Mesothelioma stage I-III.

The event-free survival is the primary endpoint for this study. This is a multicenter study and 53 Patients will be enrolled by June 2008.

• Drug: pemetrexed
  500 mg/m^2, intravenous (IV), every 21 days x 3 cycles
  Other Names:

  • LY231514
  • Alimta
• Drug: cisplatin
  75 mg/m^2, IV, every 21 days x 3 cycles

Inclusion Criteria

• Histological proven diagnosis of stages I to III mesothelioma of the pleura.
• Adequate organ function including the following: adequate bone marrow reserve, hepatic, renal, pulmonary and cardiac functions.
• No prior systemic chemotherapy
• No previous surgical resection of mesothelioma, with the exception of previous chemical pleurodesis.
• No previous radiation therapy.

Exclusion Criteria

• Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
• Serious concomitant systemic disorders
• Second active primary malignancy
• Inability to interrupt aspirin or other nonsteroidal anti-inflammatory agents for a 5-day period
• Inability or unwillingness to take folic acid, vitamin B12 supplementation, or dexamethasone