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

NCT ID: NCT02303899

Last Updated: 2021-01-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-30
• Study Completion Date: 2017-12-31

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

Conditions

Mesothelioma, Malignant

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Gemcitabine

Intervention Type: DRUG

infusion drug

Imatinib mesylate

Intervention Type: DRUG

oral drug

Interventions

Gemcitabine

infusion drug

Intervention Type: DRUG

Imatinib mesylate

oral drug

Intervention Type: DRUG

Other Intervention Names

Gemzar; Glivec

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Istituto Clinico Humanitas

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Armando Santoro, MD

Role: PRINCIPAL_INVESTIGATOR

Istituto Clinico Humanitas

Locations

Istituto Clinico Humanitas

Rozzano, MI, Italy

Countries

Italy

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Related Links

http://ctep.cancer.gov/reporting/ctc.html

27\) National Cancer Institute. Common toxicity criteria manual, version 3.0, July 16, 2003.

Other Identifiers

ONC-2014-002

Identifier Type: -

Identifier Source: org_study_id