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

January 21, 2011 updated by: Institute of Oncology Ljubljana

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

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

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

      • Ljubljana, Slovenia, 1000
        • Recruiting
        • Institute of Oncology Ljubljana
        • Contact:
        • Sub-Investigator:
          • Matjaz Zwitter, MD, PhD
        • Principal Investigator:
          • Viljem Kovac, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Cisplatin with pemetrexed

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

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
Time Frame: 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)
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
Time Frame: Outcome measures will be assessed during average time period of 18 months from enrollment

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

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Viljem Kovac, MD, Institute of Oncology Ljubljana

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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