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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2011 by Institute of Oncology Ljubljana.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Slovenian Research Agency
Information provided by:
Institute of Oncology Ljubljana
ClinicalTrials.gov Identifier:
NCT01281800
First received: January 17, 2011
Last updated: January 21, 2011
Last verified: January 2011
  Purpose

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.


Condition Intervention Phase
Mesothelioma
Procedure: Gemcitabine in long infusion
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Cisplatin With Either Alimta or Gemcitabine in Long Infusion for Mesothelioma: A Randomised Phase II Trial (AGILI Trial)

Resource links provided by NLM:


Further study details as provided by Institute of Oncology Ljubljana:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Overall survival [ Time Frame: Outcome measures will be assessed during average time period of 18 months from enrollment ] [ Designated as safety issue: Yes ]

    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.



Estimated Enrollment: 72
Study Start Date: August 2008
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.


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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01281800

Contacts
Contact: Viljem Kovac, MD +386 1 5879 504 vkovac@onko-i.si

Locations
Slovenia
Institute of Oncology Ljubljana Recruiting
Ljubljana, Slovenia, 1000
Contact: Viljem Kovac, MD    +386 1 5879 504    vkovac@onko-i.si   
Sub-Investigator: Matjaz Zwitter, MD, PhD         
Principal Investigator: Viljem Kovac, MD         
Sponsors and Collaborators
Institute of Oncology Ljubljana
Slovenian Research Agency
Investigators
Principal Investigator: Viljem Kovac, MD Institute of Oncology Ljubljana
  More Information

No publications provided

Responsible Party: Viljem Kovac, MD, Institute of Oncology Ljubljana
ClinicalTrials.gov Identifier: NCT01281800     History of Changes
Other Study ID Numbers: 22k/06/08
Study First Received: January 17, 2011
Last Updated: January 21, 2011
Health Authority: Slovenia: Ethics Committee

Additional relevant MeSH terms:
Mesothelioma
Neoplasms, Mesothelial
Adenoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Cisplatin
Gemcitabine
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014