A Phase II Study of the Association of Glivec® Plus Gemzar® in Patients With Unresectable, Refractory, Malignant Mesothelioma

• ClinicalTrials.gov Identifier: NCT00551252
• Recruitment Status: Unknown
• First Posted: October 30, 2007
• Last Update Posted: October 30, 2007
• Sponsor: Gruppo Italiano MEsotelioma
• Information provided by: Gruppo Italiano MEsotelioma

Study Description

Brief Summary:

The purpose of this study is to evaluate the antitumor activity of a combination of Imatinib mesylate and Gemcitabine in patients with unresectable malignant mesothelioma expressing either PDGFR-beta or C-kit

Condition or disease	Intervention/treatment	Phase
Mesothelioma	Drug: Imatinib mesylate plus Gemcitabine	Phase 2

Detailed Description:

TITLE "A phase II study of the association of Glivec® (Imatinib mesylate, formerly known as STI 571) plus Gemzar® (Gemcitabine) in patients with unresectable, refractory, malignant mesothelioma expressing either PDGFR-beta or C-Kit"

PURPOSE Primary objective of the phase II

> Efficacy, i.e., response rate to study drugs

Secondary objectives of the phase II

• Duration of response
• Time to progression
• Toxicity profile
• Overall survival

PRIMARY VARIABLE The primary efficacy variable for the phase II part of the study is Best Overall Tumor Response, evaluated using the "Modified RECIST criteria for assessment of response in malignant pleural mesothelioma"

SECONDARY VARIABLES

• Progression-free survival (PFS) form 1st administration onwards
• Overall survival
• Safety criteria, according to NCI-CTC criteria version 3.0

EFFICACY Objective tumor response assesed using the "Modified RECIST criteria for assessment of response in malignant pleural mesothelioma" SAFETY

• Adverse events
• Vital signs
• Clinical and biohumoral findings

TREATMENT SCHEDULE

• Gemzar 500 mg/m2, i.v., days 1 and 8 of a 21-days schedule, plus
• Glivec 400 mg/die., per os

STATISTICAL DESIGN The study follows a two-stage design, according to the Simon model. We assume that with a response rate of 5% (H0) or less the drug is likely to be ineffective, and also, that, for the drug to be effective, a target response rate of 15% (H1) is required. With a probability errors alfa of 5% and beta 20%, the calculated sample size is as reported in "PLANNED NUMBER OF PTS."

PLANNED NUMBER OF PTS. 23 or 56 patients, evaluable for efficacy. The number depends on the response rate. When 2 or more objective responses, i.e., CR or PR, are observed in the first 23 patients, the total number of patients will be increased to 56, otherwise the study will be stopped

STATISTICAL EVALUATION Efficacy and safety variables will be evaluated descriptively. Indeed, ORR estimates and its exact 95% confidence interval will be calculated. Kaplan-Meier method will be used to estimate duration of response, PFS and OS

DURATION OF TREATMENT All patients are scheduled to receive at least two cycles of chemotherapy unless there is unacceptable toxicity, progressive disease, or the patient requires or asks for withdrawal from the study Responding patients will receive treatment for 6 cycles or earlier if progression or unbearable toxicity Disease status will be re-evaluated every two cycles, using the same imaging procedures used at baseline, i.e., CT or NMR

INCLUSION CRITERIA

• Age of > 18 years and < 72 years
• Patients with a histologically proven malignant mesothelioma of the pleura or of the peritoneum, expressing either PDFGR-beta or C-Kit by immunochemistry (ICH)
• Locally advanced disease, unsuitable for curative surgical resection, or metastatic disease
• Confirmed progression of the disease according to modified REcist-criteria, documented after a first-line, systemic (premetrex+cisplatin regimen) or local treatment (i.e., intrapleuric)
• ECOG Performance Status of 0, 1 or 2
• Life expectancy of at least 3 months
• Capability of understanding the objectives of the study and giving written informed consent
• Willingness and ability to comply with study requirements
• Sufficient caloric and fluid intake, including patients under enteral or parenteral nutrition

EXCLUSION CRITERIA

• Co-existing tumors of different histologic origin, except non melanomatous localized skin cancer and/or in situ cervical carcinoma
• A history of earlier tumors of different histologic origin being in complete remission since less than 5 years
• Unresolved toxicity from prior antitumor treatment(s)
• Primary peritoneal mesothelioma

• Any of the following abnormal baseline hematological values:

  • Hb < 9 g/dL
  • WBC < 3 x 109/L
  • Neutrophils < 1.5 x 109/L
  • Platelets < 100 x 109/L
  • Serum bilirubin > 2.5 mg/dL
  • ALAT and ASAT > 3 x UNL (unless due to liver metastases)
  • Serum creatinine > 1.5 mg/dL
• Clinically relevant cardiovascular disease, i.e., myocardial infarction or other severe coronary artery diseases within the prior 6 months, cardiac arrythmia requiring medication, uncontrolled hypertension, overt cardiac failure or non compensated chronic heart disease in NYHA class II or more
• History of psychiatric disabilities, potentially interfering with the capability of giving adequate informed consent
• Pregnant or lactating women or inability/unwillingness to practice a medically approved method of contraception during study period (including 3 months following the end of treatment)
• Uncontrolled active infections
• Any condition which, in the judgement of the Investigator, would place the patient at undue risk or interfere with the results of the study

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 56 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of the Association of Glivec® (Imatinib Mesylate, Formerly Known as STI 571) Plus Gemzar® (Gemcitabine) in Patients With Unresectable, Refractory, Malignant Mesothelioma Expressing Either PDGFR-Beta or C-Kit
• Study Start Date: January 2008
• Estimated Study Completion Date: December 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: I	Drug: Imatinib mesylate plus Gemcitabine; Imatinib (400 mg daily) + Gemcitabine (500 mg/sqm, days 1 and 8 every 21 days) for a maximum of 6 cycles

Outcome Measures

Primary Outcome Measures :

1. Overall response rate [ Time Frame: Every two months ]

Secondary Outcome Measures :

1. Progression-free-survival; Overall Survival; Safety [ Time Frame: Follow-up after end of treatment will be every three months; safety will be analyzed throughout the whole study ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Age of > 18 years and < 72 years
• Patients with a histologically proven malignant mesothelioma of the pleura or of the peritoneum, expressing either PDFGR-beta or C-Kit by immunochemistry (ICH)
• Locally advanced disease, unsuitable for curative surgical resection, or metastatic disease
• Confirmed progression of the disease according to modified REcist-criteria, documented after a first-line, systemic (premetrex+cisplatin regimen) or local treatment (i.e., intrapleuric)
• ECOG Performance Status of 0, 1 or 2
• Life expectancy of at least 3 months
• Capability of understanding the objectives of the study and giving written informed consent
• Willingness and ability to comply with study requirements
• Sufficient caloric and fluid intake, including patients under enteral or parenteral nutrition

Exclusion Criteria:

• Co-existing tumors of different histologic origin, except non melanomatous localized skin cancer and/or in situ cervical carcinoma
• A history of earlier tumors of different histologic origin being in complete remission since less than 5 years
• Unresolved toxicity from prior antitumor treatment(s)
• Primary peritoneal mesothelioma

• Any of the following abnormal baseline hematological values:

  • Hb < 9 g/dL
  • WBC < 3 x 109/L
  • Neutrophils < 1.5 x 109/L
  • Platelets < 100 x 109/L
  • Serum bilirubin > 2.5 mg/dL
  • ALAT and ASAT > 3 x UNL (unless due to liver metastases)
  • Serum creatinine > 1.5 mg/dL
• Clinically relevant cardiovascular disease, i.e., myocardial infarction or other severe coronary artery diseases within the prior 6 months, cardiac arrythmia requiring medication, uncontrolled hypertension, overt cardiac failure or non compensated chronic heart disease in NYHA class II or more
• History of psychiatric disabilities, potentially interfering with the capability of giving adequate informed consent
• Pregnant or lactating women or inability/unwillingness to practice a medically approved method of contraception during study period (including 3 months following the end of treatment)
• Uncontrolled active infections
• Any condition which, in the judgement of the Investigator, would place the patient at undue risk or interfere with the results of the study

Contacts and Locations

Contacts

Contact: Camillo Porta, MD; +39-0382-501355; c.porta@smatteo.pv.it

Locations

Italy

Medical Oncology, IRCCS San Matteo University Hospital Foundation

Pavia, Italy, 27100

Principal Investigator: Camillo Porta, MD

Sponsors and Collaborators

Gruppo Italiano MEsotelioma

Investigators

• Principal Investigator: Camillo Porta, MD; Medical Oncology, IRCCS San Matteo University Hospital Foundation, pavia, Italy

More Information

Additional Information:

Italian Mesothelioma Group Homepage 

Publications:

Bertino P, Porta C, Barbone D, Germano S, Busacca S, Pinato S, Tassi G, Favoni R, Gaudino G, Mutti L. Preliminary data suggestive of a novel translational approach to mesothelioma treatment: imatinib mesylate with gemcitabine or pemetrexed. Thorax. 2007 Aug;62(8):690-5. doi: 10.1136/thx.2006.069872. Epub 2007 Feb 20.

• ClinicalTrials.gov Identifier: NCT00551252
• Other Study ID Numbers: GIMe/01/06
• First Posted: October 30, 2007
• Last Update Posted: October 30, 2007
• Last Verified: October 2007

Additional relevant MeSH terms:

Gemcitabine; Imatinib Mesylate; Mesothelioma; Mesothelioma, Malignant; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Protein Kinase Inhibitors