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Combination of Gemcitabine and Imatinib Mesylate in Pemetrexed-pretreated Patients With Pleural Mesothelioma

Primary Purpose

Mesothelioma, Malignant

Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Gemcitabine
Imatinib mesylate
Sponsored by
Istituto Clinico Humanitas
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mesothelioma, Malignant

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age of > 18 years.
  2. Histologically proven malignant mesothelioma of the pleura or of the peritoneum, expressing PDGFR-beta and/or C-kit by immunohistochemistry.
  3. Locally advanced disease, unsuitable for curative surgical resection, or metastatic disease.
  4. Confirmed progression of the disease according to modified RECIST-criteria, documented after a pemetrexed-based chemotherapy.
  5. Eastern Cooperative Oncology group (ECOG) Performance Status of 0, 1 or 2.
  6. Life expectancy of at least 3 months.
  7. Written informed consent.

Exclusion Criteria:

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

  5. Any of the following abnormal baseline hematological values:

    • Hb < 9 g/dL
    • White blood count (WBC) < 3 x 109/L
    • Neutrophils < 1.5 x 109/L
    • Platelets < 100 x 109/L
    • Serum bilirubin > 2.5 mg/dL
    • Alanine transaminase (ALAT) and Aspartate transaminase (ASAT) > 3 x upper normal limit (UNL) (unless due to liver metastases)
    • Serum creatinine > 1.5 mg/dL.
  6. Symptomatic and/or unstable pre-existing brain metastases. To be enrolled in the study, subjects must have confirmation of stable disease by MRI or computer tomography (CT) scan within 4 weeks from day 1 of cycle 1 of treatment and have central nervous system (CNS) metastases well controlled by steroids, anti - epileptics or other symptom-relieving medications.
  7. 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 New York Heart Association (NYHA) class II or more.
  8. History of psychiatric disabilities, potentially interfering with the capability of giving adequate informed consent.
  9. 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)
  10. Uncontrolled active infections.
  11. Any condition which, in the judgement of the Investigator, would place the patient at undue risk or interfere with the results of the study.

Sites / Locations

  • Istituto Clinico Humanitas

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Gemcitabine & Imatinib mesylate

Arm Description

Gemcitabine 1000 mg/m2, i.v., days 3 and 10 of a 21-days schedule; Imatinib mesylate 400 mg/die orally on days 1-5 and 8-12 of a 21-days schedule.

Outcomes

Primary Outcome Measures

anti-tumor activity of Imatinib mesylate in combination with Gemcitabine
assess the anti-tumor activity of Imatinib mesylate in combination with Gemcitabine, in terms of 3-months progression-free survival (PFS) rate

Secondary Outcome Measures

anti-tumor activity of Imatinib mesylate in combination with Gemcitabine in terms of Response Evaluation Criteria In Solid Tumors (RECIST) criteria
assess anti-tumor activity of Imatinib Mesylate (IM) in combination with GEM, in terms of objective response rate according to RECIST criteria (Modified RECIST criteria for MPM), and duration of response
anti-tumor activity of Imatinib mesylate in combination with Gemcitabine in terms of overall survival (OS).
assess anti-tumor activity of IM in combination with GEM, in terms of overall survival (OS).
safety profile of the combination according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 3
determine the safety profile of the combination according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 3
molecular profile of patients
evaluate the molecular profile of patients enrolled with Ion PGM Torrent Next-generation Sequencing platform correlating the molecular profiles identified with clinical characteristics and survival data of patients.

Full Information

First Posted
November 19, 2014
Last Updated
January 20, 2021
Sponsor
Istituto Clinico Humanitas
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1. Study Identification

Unique Protocol Identification Number
NCT02303899
Brief Title
Combination of Gemcitabine and Imatinib Mesylate in Pemetrexed-pretreated Patients With Pleural Mesothelioma
Official Title
A Phase II Study of the Combination of Gemcitabine and Imatinib Mesylate in Pemetrexed-pretreated Patients With Malignant Pleural Mesothelioma
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
November 2014 (Actual)
Primary Completion Date
December 2015 (Actual)
Study Completion Date
December 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Istituto Clinico Humanitas

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a phase II, monocentric study of the combination of gemcitabine and imatinib mesylate in pemetrexed-pretreated patients with MPM expressing PDGFR-beta and/or C-kit by Immunohistochemistry (IHC). Treatment will be done until disease progression, or patient refusal or withdrawal of patient consent, or unacceptable toxicity
Detailed Description
Pemetrexed-pretreated patients with MPM expressing PDGFR-beta and/or C-kit by IHC will receive chemotherapy as follow : Gemcitabine 1000 mg/m2, i.v., days 3 and 10 of a 21-days schedule; Imatinib mesylate 400 mg/die orally on days 1-5 and 8-12 of a 21-days schedule. Treatment repeats every 21 days in the absence of disease progression, patient refusal or withdrawal of patient consent, or unacceptable toxicity. The molecular profile of patients enrolled will be evaluated with Ion Personal Genome Machine (PGM) Torrent Next-generation Sequencing platform in order to individuate potential predictive biomarkers and to improve the understanding of the molecular biology of these rare tumors. A correlation among the molecular profiles identified, clinical characteristics, and survival data of patients will be done

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mesothelioma, Malignant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Gemcitabine & Imatinib mesylate
Arm Type
Experimental
Arm Description
Gemcitabine 1000 mg/m2, i.v., days 3 and 10 of a 21-days schedule; Imatinib mesylate 400 mg/die orally on days 1-5 and 8-12 of a 21-days schedule.
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Other Intervention Name(s)
Gemzar
Intervention Description
infusion drug
Intervention Type
Drug
Intervention Name(s)
Imatinib mesylate
Other Intervention Name(s)
Glivec
Intervention Description
oral drug
Primary Outcome Measure Information:
Title
anti-tumor activity of Imatinib mesylate in combination with Gemcitabine
Description
assess the anti-tumor activity of Imatinib mesylate in combination with Gemcitabine, in terms of 3-months progression-free survival (PFS) rate
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
anti-tumor activity of Imatinib mesylate in combination with Gemcitabine in terms of Response Evaluation Criteria In Solid Tumors (RECIST) criteria
Description
assess anti-tumor activity of Imatinib Mesylate (IM) in combination with GEM, in terms of objective response rate according to RECIST criteria (Modified RECIST criteria for MPM), and duration of response
Time Frame
16 weeks
Title
anti-tumor activity of Imatinib mesylate in combination with Gemcitabine in terms of overall survival (OS).
Description
assess anti-tumor activity of IM in combination with GEM, in terms of overall survival (OS).
Time Frame
30 months
Title
safety profile of the combination according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 3
Description
determine the safety profile of the combination according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 3
Time Frame
16 weeks
Title
molecular profile of patients
Description
evaluate the molecular profile of patients enrolled with Ion PGM Torrent Next-generation Sequencing platform correlating the molecular profiles identified with clinical characteristics and survival data of patients.
Time Frame
baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age of > 18 years. Histologically proven malignant mesothelioma of the pleura or of the peritoneum, expressing PDGFR-beta and/or C-kit by immunohistochemistry. Locally advanced disease, unsuitable for curative surgical resection, or metastatic disease. Confirmed progression of the disease according to modified RECIST-criteria, documented after a pemetrexed-based chemotherapy. Eastern Cooperative Oncology group (ECOG) Performance Status of 0, 1 or 2. Life expectancy of at least 3 months. Written informed consent. 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 for 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 White blood count (WBC) < 3 x 109/L Neutrophils < 1.5 x 109/L Platelets < 100 x 109/L Serum bilirubin > 2.5 mg/dL Alanine transaminase (ALAT) and Aspartate transaminase (ASAT) > 3 x upper normal limit (UNL) (unless due to liver metastases) Serum creatinine > 1.5 mg/dL. Symptomatic and/or unstable pre-existing brain metastases. To be enrolled in the study, subjects must have confirmation of stable disease by MRI or computer tomography (CT) scan within 4 weeks from day 1 of cycle 1 of treatment and have central nervous system (CNS) metastases well controlled by steroids, anti - epileptics or other symptom-relieving medications. 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 New York Heart Association (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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Armando Santoro, MD
Organizational Affiliation
Istituto Clinico Humanitas
Official's Role
Principal Investigator
Facility Information:
Facility Name
Istituto Clinico Humanitas
City
Rozzano
State/Province
MI
ZIP/Postal Code
20089
Country
Italy

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
not planned
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Combination of Gemcitabine and Imatinib Mesylate in Pemetrexed-pretreated Patients With Pleural Mesothelioma

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