Clinical trial NCT02303899: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mesothelioma, Malignant
Lead sponsor: Istituto Clinico Humanitas
Sponsor class: OTHER
First posted: 2014-12-01
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: anti-tumor activity of Imatinib mesylate in combination with Gemcitabine
timeFrame: 12 weeks
Secondary outcomes:
measure: anti-tumor activity of Imatinib mesylate in combination with Gemcitabine in terms of Response Evaluation Criteria In Solid Tumors (RECIST) criteria
timeFrame: 16 weeks
measure: anti-tumor activity of Imatinib mesylate in combination with Gemcitabine in terms of overall survival (OS).
timeFrame: 30 months
measure: safety profile of the combination according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 3
timeFrame: 16 weeks
measure: molecular profile of patients
timeFrame: baseline
Other outcomes:
Locations:
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: MI
Study officials:
affiliation: Istituto Clinico Humanitas
name: Armando Santoro, MD
role: PRINCIPAL_INVESTIGATOR
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