Clinical trial NCT01243632: Gemcitabine in Long Infusion and Cisplatin for Malignant Pleural Mesothelioma Treatment
Official title: A Phase II Trial of Low-dose Gemcitabine in Prolonged Infusion and Cisplatin in Treatment of Malignant Pleural Mesothelioma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malignant Pleural Mesothelioma
Keywords: malignant pleural mesothelioma
chemotherapy
gemcitabine
cisplatin
long infusion
Lead sponsor: Institute of Oncology Ljubljana
Sponsor class: OTHER
Collaborators: name: Ministry of Higher Education, Science and Technology, Solvenia
First posted: 2010-11-18
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Combination of gemcitabine-cisplatin was one of the most effective chemotherapy treatment in mesothelioma patients. However, median survival of this patient group was only about 12 months. With intent to find more effective treatment the investigators performed phase II study with gemcitabine in low dose (130-250 mg/m2) in 6-hours (prolonged) infusion in combination with cisplatin in advanced non-small cell lung cancer (Zwitter et al. Anticancer Drugs 2005;16:1129-34). After favourable experience, the investigators decided to explore such regiment in patients with malignant pleural mesothelioma (MPM) as well.

Detailed description: The purpose of this study is to evaluate new regimen of treatment for its activity in malignant pleural mesothelioma (MPM). The primary objectives of the trial are assessing the treatment toxicity, response rate, and progress free survival; secondary objectives are assessment of overall survival and quality of life.

Inclusion criteria:

* Biopsy-proven diagnosis of MPM
* Inoperable for anatomic or physiological reason
* Measurable and previously unirradiated lesion
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 - 2
* Adequate haematopoietic, liver, and kidney function.
* Signed informed consent for participation in the trial

Exclusion criteria:

* Significant medical co-morbidity
* Pregnant or lactating women
* History of the cancer in the previous 10 years or breast cancer ever.

The general treatment schedule will be identical for all patients: gemcitabine in 6-hours infusion on days 1 and 8, and cisplatin at 75 mg/m2 on day 2 of a 3-weekly cycle with standard antiemetic treatment using metoclopramide, dexamethasone, aprepitant, and granisetron. After 4 cycles, patients not in progression and without serious toxicity continued with additional 2 cycles of monotherapy with gemcitabine in prolonged infusion.

National Cancer Institute Common Toxicity Criteria (NCI CTC), version 2.0 will be used for grading the toxicity. In the day of administration of the cytotoxic drug complete blood cell count and chemistry panel will be performed, and the treatment will be reduced or avoided in the event of bone marrow suppression or decline in renal clearance. In cases of Grade I (NCI CTC, vs. 2.0) neutropenia and/or thrombocytopenia, the dose of gemcitabine will be reduced to 75%; the drug will be omitted with Grade II or greater neutro/thrombocytopenia. Cisplatin will be omitted in cases of Grade ≥ II nephrotoxicity and/or grade III nausea or vomiting.

Eligibility criteria: Inclusion Criteria:

* Biopsy-proven diagnosis of malignant pleural mesothelioma
* Inoperable for anatomic or physiological reason
* Measurable and previously unirradiated lesion
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 - 2
* Adequate haematopoietic, liver, and kidney function.
* Signed informed consent for participation in the trial

Exclusion Criteria:

* Significant medical co-morbidity
* Pregnant or lactating women
* History of the cancer in the previous 10 years or breast cancer ever.

Primary outcomes:
measure: Response rate
timeFrame: Computerized tomography (CT) measurement of disease will be performed after 2nd cycle of chemotherapy and at the end of the treatment
Secondary outcomes:
measure: Safety and tolerability
timeFrame: During the study
Other outcomes:
Locations:
city: Ljubljana
country: Slovenia
facility: Institute of Oncology Ljubljana
Study officials:
affiliation: Institute of Oncology Ljubljana
name: Matjaz Zwitter, MD, PhD
role: STUDY_DIRECTOR
References: