Cisplatin With Alimta or Gemcitabine in Long Infusion for Mesothelioma

NCT ID: NCT01281800

Last Updated: 2011-01-24

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-08-31

Brief Summary

This is a randomised Phase II clinical trial to assess and compare efficacy and safety profile of cisplatin and pemetrexed against cisplatin and low-dose gemcitabine in long infusion.

Detailed Description

Combination of pemetrexed and cisplatin is now considered the standard systemic treatment for mesothelioma. Three arguments against such a position are: 1. Pemetrexed in combination with cisplatin was registered for mesothelioma on the basis of superiority over cisplatin alone, a clearly suboptimal control arm; 2. Several Phase II trials of gemcitabine in standard doses or as low-dose in long infusion in combination with cisplatin have shown at least comparable activity; 3. Due to high cost, pemetrexed is not available to many patients in countries with limited health care resources. During the past five years, our research team in Ljubljana conducted a Phase II trial of low-dose gemcitabine (250 mg/m2) in 6-hours infusion and cisplatin for patients with mesothelioma. In an unselected population of patients including those in poor performance status, elderly, patients with advanced extrathoracic disease and patients in progression after previous chemotherapy, the response rate was 54%, and median survival was 16.5 months. On the basis of this favourable experience and in search of cost-effective treatment for mesothelioma, we here propose a randomised Phase II clinical trial to compare efficacy and safety profile of cisplatin and pemetrexed against cisplatin and low-dose gemcitabine in long infusion. The primary endpoints are response rate and time to progression; secondary endpoints are survival, toxicity and quality of life.

Conditions

Mesothelioma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cisplatin with pemetrexed

Group Type: ACTIVE_COMPARATOR

Gemcitabine in long infusion

Intervention Type: PROCEDURE

TREATMENT A:

Day 1: Pemetrexed 500 mg/m2 Cisplatin 75 mg/m2 Cycle every 3 weeks. Supportive treatment: folic acid [Tifol 400 mg tbl (350-1000 mg), beginning 7 days before CT, every day, till 3 week after the KT], vitamin B-12 [OH-B12 i.m., beginning in 7 days before CT, than at 3. + 6. cycles of KT + 9. week after the KT], corticosteroids, hydration, antiemetic, LMW heparin as thromboprophylaxis.

In the absence of progression, 4 cycles of chemotherapy with pemetrexed and cisplatin will be given, followed by two additional cycles of pemetrexed as monotherapy.

TREATMENT B:

Days 1 and 8: gemcitabine 250 mg/m2 in 6 hours day 2: cisplatin 75 mg/m2 Cycle every 3 weeks. Supportive treatment: corticosteroids, hydration, antiemetics, LMW heparin as thromboprophylaxis.

In the absence of progression, 4 cycles of chemotherapy with gemcitabine and cisplatin will be given, followed by two additional cycles of gemcitabine alone as monotherapy.

Cisplatin with gemcitabine in long infusion

Group Type: EXPERIMENTAL

Gemcitabine in long infusion

Intervention Type: PROCEDURE

TREATMENT A:

Day 1: Pemetrexed 500 mg/m2 Cisplatin 75 mg/m2 Cycle every 3 weeks. Supportive treatment: folic acid [Tifol 400 mg tbl (350-1000 mg), beginning 7 days before CT, every day, till 3 week after the KT], vitamin B-12 [OH-B12 i.m., beginning in 7 days before CT, than at 3. + 6. cycles of KT + 9. week after the KT], corticosteroids, hydration, antiemetic, LMW heparin as thromboprophylaxis.

In the absence of progression, 4 cycles of chemotherapy with pemetrexed and cisplatin will be given, followed by two additional cycles of pemetrexed as monotherapy.

TREATMENT B:

Days 1 and 8: gemcitabine 250 mg/m2 in 6 hours day 2: cisplatin 75 mg/m2 Cycle every 3 weeks. Supportive treatment: corticosteroids, hydration, antiemetics, LMW heparin as thromboprophylaxis.

In the absence of progression, 4 cycles of chemotherapy with gemcitabine and cisplatin will be given, followed by two additional cycles of gemcitabine alone as monotherapy.

Interventions

Gemcitabine in long infusion

TREATMENT A:

Day 1: Pemetrexed 500 mg/m2 Cisplatin 75 mg/m2 Cycle every 3 weeks. Supportive treatment: folic acid [Tifol 400 mg tbl (350-1000 mg), beginning 7 days before CT, every day, till 3 week after the KT], vitamin B-12 [OH-B12 i.m., beginning in 7 days before CT, than at 3. + 6. cycles of KT + 9. week after the KT], corticosteroids, hydration, antiemetic, LMW heparin as thromboprophylaxis.

In the absence of progression, 4 cycles of chemotherapy with pemetrexed and cisplatin will be given, followed by two additional cycles of pemetrexed as monotherapy.

TREATMENT B:

Days 1 and 8: gemcitabine 250 mg/m2 in 6 hours day 2: cisplatin 75 mg/m2 Cycle every 3 weeks. Supportive treatment: corticosteroids, hydration, antiemetics, LMW heparin as thromboprophylaxis.

In the absence of progression, 4 cycles of chemotherapy with gemcitabine and cisplatin will be given, followed by two additional cycles of gemcitabine alone as monotherapy.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• histologically proven mesothelioma. While local histopathology exam is sufficient to register a patient for the trial, all biopsies will be subject to central review (please see Section 5.3.)
• no history of other malignancy; or in complete remission for > 3 years if previously treated for other malignancy;
• chemo-naive;
• performance status ≥ 70% (Karnofsky); or ECOG 0 - 2 ;
• no peripheral neuropathy grade 2 or more (common toxicity criteria - CTC, NCI), unless mechanical in origin;
• no vascular disease grade 2 or more (NCI CTC ver.3);
• hemoglobin > 100 g/L;
• neutrophils > 2.0 g/L;
• platelets > 100 x 109 /L;
• kidney function: creatinine within normal limits + ECC > 60 mL/min; or ECC > 100 mL/min;
• liver function: bilirubin < 1.25 x UNL; AST/ALT < 2 x UNL;
• cardiac compensation;
• no active infection or other serious concomitant disease;
• women are not pregnant
• patient's understanding of the disease and treatment and written informed consent.

Exclusion Criteria

• significant medical co-morbidity

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

Sponsors

Slovenian Research Agency

OTHER

Sponsor Role: collaborator

Institute of Oncology Ljubljana

OTHER

Sponsor Role: lead

Responsible Party

Institute of Oncology Ljubljana

Principal Investigators

Viljem Kovac, MD

Role: PRINCIPAL_INVESTIGATOR

Institute of Oncology Ljubljana

Locations

Institute of Oncology Ljubljana

Ljubljana, , Slovenia

Site Status: RECRUITING

Countries

Slovenia

Central Contacts

Viljem Kovac, MD

Role: CONTACT

vkovac@onko-i.si

+386 1 5879 504

Facility Contacts

Viljem Kovac, MD

Role: primary

vkovac@onko-i.si

+386 1 5879 504

Other Identifiers

22k/06/08

Identifier Type: -

Identifier Source: org_study_id