Pemetrexed Plus Cisplatin Neoadjuvant Therapy Followed By Surgery and Radiation in Mesothelioma - Full Text View

Sponsor:	Eli Lilly and Company
Information provided by:	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT00192010

Purpose

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.

Condition	Intervention	Phase
Mesothelioma	Drug: pemetrexed Drug: cisplatin	Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase II Trial of Neoadjuvant ALIMTA Plus Cisplatin Followed by Surgery and Radiation in the Treatment of Pleural Mesothelioma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Mesothelioma

Drug Information available for: Cisplatin Pemetrexed Pemetrexed disodium

U.S. FDA Resources

Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:

Event-free Survival (EFS) [ Time Frame: date of first dose of study drug to first observation of disease progression, death from any cause, discontinuation of treatment (up to 43 months) ] [ Designated as safety issue: Yes ]
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.

Secondary Outcome Measures:

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.

Enrollment:	54
Study Start Date:	June 2005
Study Completion Date:	February 2010
Primary Completion Date:	February 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Pemetrexed + Cisplatin Preoperative chemotherapy consisting of pemetrexed 500 mg/m^2 and cisplatin 75 mg/m^2 administered intravenously on Day 1 for 3 21-day cycles followed by surgery (extrapleural pneumonectomy). After 4-12 weeks from surgery, radiation therapy is administered at a total dose of 50.4 Gray (Gy) in 28 fractions of 1.8 Gy per day.	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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00192010

Locations

Italy
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Mestre/Venezia, Italy, 30170
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Milano, Italy, 20141
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Padova, Italy, 35100
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Rome, Italy, 00128

Sponsors and Collaborators

Eli Lilly and Company

Investigators

Study Chair:

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Eli Lilly and Company

More Information

No publications provided

Responsible Party:	Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier:	NCT00192010 History of Changes
Other Study ID Numbers:	8848, H3E-IT-S079
Study First Received:	September 12, 2005
Results First Received:	February 9, 2011
Last Updated:	May 5, 2011
Health Authority:	Italy: Ministry of Health

Additional relevant MeSH terms:

Mesothelioma
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial
Pemetrexed
Cisplatin
Antineoplastic Agents

Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on February 12, 2012