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

October 29, 2007 updated by: Gruppo Italiano MEsotelioma

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

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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

56

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
      • Pavia, Italy, 27100
        • Medical Oncology, IRCCS San Matteo University Hospital Foundation

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Overall response rate
Time Frame: Every two months
Every two months

Secondary Outcome Measures

Outcome Measure
Time Frame
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
Follow-up after end of treatment will be every three months; safety will be analyzed throughout the whole study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gruppo Italiano MEsotelioma

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2008

Study Completion (Anticipated)

December 1, 2009

Study Registration Dates

First Submitted

October 29, 2007

First Submitted That Met QC Criteria

October 29, 2007

First Posted (Estimate)

October 30, 2007

Study Record Updates

Last Update Posted (Estimate)

October 30, 2007

Last Update Submitted That Met QC Criteria

October 29, 2007

Last Verified

October 1, 2007

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GIMe/01/06

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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