Primary Outcome Measure:
- Anti-tumor activity of Imatinib mesylate in combination with Gemcitabine [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
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 [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
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). [ Time Frame: 30 months ] [ Designated as safety issue: No ]
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 [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
determine the safety profile of the combination according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 3
- Molecular profile of patients [ Time Frame: baseline ] [ Designated as safety issue: No ]
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.
Eligibility Criteria
- Inclusion Criteria:
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- 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.
