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

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ClinicalTrials.gov Identifier: NCT02303899
Recruitment Status : Completed
First Posted : December 1, 2014
Last Update Posted : January 22, 2021
Sponsor:
Information provided by (Responsible Party):
Istituto Clinico Humanitas

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

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

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of the Combination of Gemcitabine and Imatinib Mesylate in Pemetrexed-pretreated Patients With Malignant Pleural Mesothelioma
Actual Study Start Date : November 2014
Actual Primary Completion Date : December 2015
Actual Study Completion Date : December 2017


Arm Intervention/treatment
Experimental: Gemcitabine & Imatinib mesylate
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.
Drug: Gemcitabine
infusion drug
Other Name: Gemzar

Drug: Imatinib mesylate
oral drug
Other Name: Glivec




Primary Outcome Measures :
  1. anti-tumor activity of Imatinib mesylate in combination with Gemcitabine [ Time Frame: 12 weeks ]
    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 :
  1. anti-tumor activity of Imatinib mesylate in combination with Gemcitabine in terms of Response Evaluation Criteria In Solid Tumors (RECIST) criteria [ Time Frame: 16 weeks ]
    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

  2. anti-tumor activity of Imatinib mesylate in combination with Gemcitabine in terms of overall survival (OS). [ Time Frame: 30 months ]
    assess anti-tumor activity of IM in combination with GEM, in terms of overall survival (OS).

  3. safety profile of the combination according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 3 [ Time Frame: 16 weeks ]
    determine the safety profile of the combination according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 3

  4. molecular profile of patients [ Time Frame: baseline ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02303899


Locations
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Italy
Istituto Clinico Humanitas
Rozzano, MI, Italy, 20089
Sponsors and Collaborators
Istituto Clinico Humanitas
Investigators
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Principal Investigator: Armando Santoro, MD Istituto Clinico Humanitas
Publications:

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Responsible Party: Istituto Clinico Humanitas
ClinicalTrials.gov Identifier: NCT02303899    
Other Study ID Numbers: ONC-2014-002
First Posted: December 1, 2014    Key Record Dates
Last Update Posted: January 22, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: not planned
Additional relevant MeSH terms:
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Mesothelioma
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial
Gemcitabine
Imatinib Mesylate
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