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

This study has been completed.

Sponsor:

Information provided by:

Eli Lilly and Company

ClinicalTrials.gov Identifier:

NCT00192010

First received: September 12, 2005

Last updated: May 5, 2011

Last verified: May 2011

History of Changes

Results First Received: February 9, 2011

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Single Group Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Mesothelioma
Interventions:	Drug: pemetrexed Drug: cisplatin

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
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.

Participant Flow: Overall Study

	Pemetrexed + Cisplatin
STARTED	54
COMPLETED	22
NOT COMPLETED	32
Adverse Event	1
Death	11
Lack of Efficacy	16
Protocol Violation	2
Physician Decision	1
Withdrawal by Subject	1

Baseline Characteristics

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Reporting Groups

	Description
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.

Baseline Measures

	Pemetrexed + Cisplatin
Number of Participants [units: participants]	54
Age [units: years] Mean ± Standard Deviation	61.8 ± 8.1
Gender [units: participants]
Female	7
Male	47
Race/Ethnicity, Customized [units: Participants]
Caucasian	54
Other	0
Region of Enrollment [units: participants]
Italy	54
Pulse Rate [units: Beats per minute (bpm)] Mean ± Standard Deviation	78.9 ± 12.2
Systolic Blood Pressure [units: millimeters of mercury (mmHg)] Mean ± Standard Deviation	130.1 ± 14.6
Diastolic Blood Pressure [units: millimeters of mercury (mmHg)] Mean ± Standard Deviation	80.0 ± 10.1
Height [units: centimeters (cm)] Mean ± Standard Deviation	169.7 ± 7.4
Weight [units: kiliograms (kg)] Mean ± Standard Deviation	74.2 ± 11.9
Body Surface Area (BSA) [units: square meters (m^2)] Mean ± Standard Deviation	1.85 ± 0.17
Eastern Cooperative Oncology Group (ECOG) Performance Status ^[1] [units: Participants]
0	34
1	20
2	0
>=3	0
Pregnancy Test ^[2] [units: Participants]
Positive	0
Negative	1
Not Applicable	53
Stress Echocardiogram ^[3] [units: Participants]
Ventricular Ejection Function (VEF) <45%	0
VEF >=45%	49
Not Done	5
Electrocardiogram (ECG) ^[4] [units: Participants]
Normal	41
Abnormal, Not Clinically Significant (NCS)	0
Abnormal, Clinically Significant (CS)	8
Not Done	5
Radionuclide Stress Test ^[5] [units: Participants]
Normal	0
Abnormal, Not Clinically Significant (NCS)	0
Abnormal, Clinically Significant (CS)	1
Not Done	53
Exercise Stress Test to Maximal Exercise Level ^[6] [units: Participants]
Normal	2
Abnormal, Not Clinically Significant (NCS)	0
Abnormal, Clinically Significant (CS)	0
Not Done	52
Forced Expiratory Volume in 1 Second [units: Participants]
<=0.8 liters	0
>0.8 liters	54
Diffusion Capacity of Carbon Monoxide, Single Breath [units: Participants]
<=35% (predicted)	0
>35% (predicted)	50
Missing	4
Carbon Dioxide Partial Pressure (pCO2) [units: Participants]
<=50 air/bone gap	44
>50 air/bone gap	0
Missing	10
Primary Tumor Staging ^[7] [units: Participants]
TX	0
T0	0
T1	13
T2	12
T3	29
Regional Lymh Nodes Staging ^[8] [units: Participants]
N0	43
N1	4
N2	7
Distant Metastasis Staging ^[9] [units: Participant]
MX	0
M0	54
M1	0
Prior Chemotherapy [units: Participants]
No	54
Yes	0
Prior Radiotherapy [units: Participants]
No	54
Yes	0
Prior Surgery [units: Participants]
No	54
Yes	0
Basis for Diagnosis Histopathological [units: Participants]	54
Pathological Diagnosis [units: Participants]
Other	6
Epithelial Mesothelioma	48
Sarcomatoid Mesothelioma	0
Time from Diagnosis [units: months] Mean ± Standard Deviation	0.9 ± 0.7

[1]	Classifies patients according to their functional impairment. Scores range from 0 (Fully Active) to 5 (Death). 0 - Fully Active; 1 - Ambulatory, Restricted Strenuous Activity; 2 - Ambulatory, No Work Activities; 3 - Partially Confined to Bed, Limited Self Care; 4 - Completely Disabled.
[2]	Not Applicable (N/A) response equals males, menopausal women, or women who are otherwise unable to bear children.
[3]	Echocardiogram is an ultrasound technique used to gather information about the heart. Ejection fraction refers to the proportion of the volume of blood in the ventricles at the end of diastole that is ejected during systole; it is the stroke volume divided by the end-diastolic volume, often expressed as a percentage.
[4]	ECG interprets the heart's electrical activity over time as captured and recorded by skin electrodes. Normal result: no sinus rhythm alteration, no cardiac axis deviation, no ECG layout alteration (normal P waves, normal PR interval, QRS complex, QT interval, ST segment, T wave and U wave); Abnormal, Not Clinically Significant result: impairment of at least one of the above reported parameters without evidence of clinical signs and symptoms; Abnormal, Clinically Significant result: impairment of at least one of the above reported parameters with evidence of clinical signs and symptoms.
[5]	Nuclear medicine test to measure heart performance during exercise. Normal result-left ventricular ejection fraction range of 50-80%; no area of abnormal wall motion (hypokinesis or dyskinesis); peak filling rates between 2.4 and 3.6 end diastolic volume per second, and time to peak filling rate of 135-212 milliseconds; Abnormal, Not Clinically Significant result: Impairment of at least one of the above reported parameters without clinical signs and symptoms; Abnormal, Clinically Significant result: Alteration of at least one of the above reported parameters with clinical signs and symptoms.
[6]	Test to measure heart performance during exercise. Normal result: No impairment of ECG layout changes, blood pressure value alternations; Abnormal, Not Clinically Significant result: Impairment of at least one of the above reported parameters without evidence of clinical signs and symptoms; Abnormal, Clinically Significant result: Impairment of at least one of the above reported parameters with evidence of clinical signs and symptoms.
[7]	TX: Primary tumor cannot be assessed; T0: No evidence of primary tumor; T1: Tumor involves ipsilateral parietal pleura, with or without focal involvement of visceral pleura; T2: Tumor involves any of ipsilateral pleural surfaces with ≥1 of the following: confluent visceral pleural tumor, invasion of diaphragmatic muscle, invasion of lung parenchyma; T3: Tumor involves any of ipsilateral pleural surface, with ≥1 of the following: invasion of endothoracic fascia, invasion in mediastinal fat, solitary focus of tumor invading soft tissues of chest wall, non-transmural involvement of pericardium.
[8]	NX: Regional lymph nodes cannot be assessed; N0: No regional lymph node metastases; N1: Metastases in the ipsilateral bronchopulmonary and/or the hilar lymph node; N2: Metastases in the subcarinal lymph node(s) and/or ipsilateral internal mammary or mediastinal lymph node(s); N3: Metastases in the contralateral mediastinal, internal mammary, or hilar lymph node(s) and/or the ipsilateral or contralateral supraclavicular or scalene lymph node(S).
[9]	MX: Distant metastases cannot be assessed; M0: No distant metastasis; M1: Distant metastasis.

Outcome Measures

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1. Primary:

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) ]

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2. Secondary:

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) ]

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3. Secondary:

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) ]

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4. Secondary:

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) ]

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5. Secondary:

Time to Progressive Disease [ Time Frame: Date of first dose of study drug to first observation of progressive disease (up to 44.6 months) ]

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6. Secondary:

Overall Survival (OS) [ Time Frame: date of first dose of study drug to date of death from any cause (up to 52.8 months) ]

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7. Secondary:

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) ]

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8. Secondary:

Complete Pathological Response Rate [ Time Frame: date of first dose of study drug to date of surgery (up to 4.1 months) ]

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9. Secondary:

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) ]

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10. Secondary:

Number of Participants With Adverse Events (Pharmacology Toxicity) [ Time Frame: baseline up to 676 days ]

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11. Post-Hoc:

Duration of Response [ Time Frame: date of first objective status assessment of CR or PR to date of progression or death as a result of any cause (up to 38.6 months) ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
phone: 800-545-5979

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

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