Cisplatin With Alimta or Gemcitabine in Long Infusion for Mesothelioma (AGILI)

Cisplatin With Either Alimta or Gemcitabine in Long Infusion for Mesothelioma: A Randomised Phase II Trial (AGILI Trial)

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.

Study Overview

• Status: Unknown
• Conditions: Mesothelioma
• Intervention / Treatment: Procedure: 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.

• Study Type: Interventional
• Enrollment (Anticipated): 72
• Phase: Phase 2

Contacts and Locations

Study Locations

• Slovenia
  • Ljubljana, Slovenia, 1000
    • Recruiting
    • Institute of Oncology Ljubljana
    • Contact: Viljem Kovac, MD; Phone Number: +386 1 5879 504; Email: vkovac@onko-i.si
    • Sub-Investigator: Matjaz Zwitter, MD, PhD
    • Principal Investigator: Viljem Kovac, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cisplatin with pemetrexed	Procedure: 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.
Experimental: Cisplatin with gemcitabine in long infusion	Procedure: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Efficacy of the treatment will be measured by response rate (RR) and progression free survival (PFS) using modified RECIST criteria for assessment of response in malignant pleural mesothelioma	CT measurement of disease will be performed after 2nd cycle of chemotherapy, at the end of the treatment and during follow up period up to progression (total average 8 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Efficacy of the treatment will be measured also by overall survival (OS). Safety and tolerability will be assessed by monitoring the adverse events during treatment and follow-up phase and graded according the NCI Common Toxicity Criteria (CTC), version 3.0. Quality of life (QOL) will be assessed with performance status (Karnofsky) and with Lung Cancer Symptom Scale (LCSS) - Observer and patient scale.	Outcome measures will be assessed during average time period of 18 months from enrollment

Collaborators and Investigators

• Sponsor: Institute of Oncology Ljubljana
• Collaborators: Slovenian Research Agency
• Investigators: Principal Investigator: Viljem Kovac, MD, Institute of Oncology Ljubljana

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Anticipated): August 1, 2014

Study Registration Dates

• First Submitted: January 17, 2011
• First Submitted That Met QC Criteria: January 21, 2011
• First Posted (Estimate): January 24, 2011

Study Record Updates

• Last Update Posted (Estimate): January 24, 2011
• Last Update Submitted That Met QC Criteria: January 21, 2011
• Last Verified: January 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Adenoma; Neoplasms, Mesothelial; Pleural Neoplasms; Mesothelioma; Mesothelioma, Malignant; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine
• Other Study ID Numbers: 22k/06/08