Palliative Treatment With Liposomal Doxorubicin Plus Cisplatin for Patients With Malignant Pleural Mesothelioma
Primary Purpose
Malignant Pleural Mesothelioma
Status
Unknown status
Phase
Phase 2
Locations
Mexico
Study Type
Interventional
Intervention
Liposomal doxorubicin
Cisplatin
Sponsored by
About this trial
This is an interventional treatment trial for Malignant Pleural Mesothelioma focused on measuring Malignant pleural mesothelioma, Liposomal doxorubicin, Progression free survival, Patients who received LD 60mg/m2 plus cisplatin 80 mg/m2 every 4 weeks for 6 cycles, Patients with epithelial, sarcomatoid or biphasic histological confirmed diagnosis of MPM
Eligibility Criteria
Inclusion Criteria:
- Patients with epithelial, sarcomatoid or biphasic histological confirmed diagnosis of MPM from the Instituto Nacional de Cancerología and the Instituto Nacional de Enfermedades Respiratorias
- ECOG functional status 0 or 2
- No renal function alteration (GFR >50%)
- No hepatic function alteration
- Leucocytes more than 2,000/mcl
- Hemoglobin more than 10mg/dL
- Platelets more than 100,000/mcl
Exclusion Criteria:
- Patients who had received previous chemotherapy for MPM
- Patients who do not accept the treatment
Sites / Locations
- National Institute of Cancerología
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Liposomal doxorubicin
Arm Description
Thirty patients with MPM who received liposomal doxorubicin 60mg/m2 plus cisplatin 80 mg/m2 every 4 weeks for 6 cycles.
Outcomes
Primary Outcome Measures
Progression free survival
Over-all survival
Secondary Outcome Measures
Full Information
NCT ID
NCT00886028
First Posted
April 20, 2009
Last Updated
April 21, 2009
Sponsor
National Institute of Cancerología
1. Study Identification
Unique Protocol Identification Number
NCT00886028
Brief Title
Palliative Treatment With Liposomal Doxorubicin Plus Cisplatin for Patients With Malignant Pleural Mesothelioma
Official Title
"Phase II Study: Palliative Treatment With Liposomal Doxorubicin Plus Cisplatin for Patients With Malignant Pleural Mesothelioma "
Study Type
Interventional
2. Study Status
Record Verification Date
April 2009
Overall Recruitment Status
Unknown status
Study Start Date
September 2006 (undefined)
Primary Completion Date
April 2009 (Anticipated)
Study Completion Date
June 2009 (Anticipated)
3. Sponsor/Collaborators
Name of the Sponsor
National Institute of Cancerología
4. Oversight
5. Study Description
Brief Summary
Liposomal doxorubicin consists on doxorubicin encapsulated in liposomes that are composed of phosphatidylcholine and cholesterol. Liposomal doxorubicin can extravasate into tumors with abnormal vascular endothelium but may not penetrate normal tissues lowering its toxicity and increasing its efficiency. Combining Liposomal doxorubicin with cisplatin could be an effective new chemotherapy treatment for malignant pleural mesothelioma .
Hypothesis:
Liposomal doxorubicin combined with cisplatin could increase response rates to chemotherapy, progression free survival and overall survival in patients with malignant pleural mesothelioma.
Detailed Description
Background:
Malignant pleural mesothelioma (MPM) is an invasive primary neoplasm associated with a rapid progression. It is usually diagnosed in the fifth to seventh decades of life, with a strong male predominance. 80% of the patients with MPM have a history of asbestos exposure. MPM develops only in 10% of the people with asbestos exposure, suggesting that other factors may be important in the development of this malignancy. MPM is classified into three pathological types: epithelial, sarcomatoid, and mixed. The epithelial type represents 50% of all the cases whether the sarcomatoid type the15%. Clinically the sarcomatoid type is related to a poorer prognosis compared with epithelial or mixed types MPM presents unique challenges with regard to diagnosis, staging, and treatment. Survival rates are approximately 6 months in patients without surgical treatment. 90% of the patients with MPM are not candidates for a surgical treatment because they arrived at advanced stages or with a poor lung function. In addition, surgery as a single modality has failed to improve survival, and several researches have explored the use of combined modality therapy incorporating radiation and chemotherapy. Given that the prognosis for patients with advanced MPM is poor regardless of the type of anticancer treatment, palliation of symptoms has been the primary goal. Chemotherapy remains the main palliative therapeutic modality, although either surgical intervention or local radiation therapy may be useful for the local control of pain or symptoms often associated with pleural fluid accumulation.
Most single chemotherapeutic agents have been tested in MPM obtaining response rates of < 20%. The impact of chemotherapy on the survival of patients with MPM remains uncertain. Platinum analogues have been extensively studied in MPM both single and combined regimens. There have been studies of patients with MPM treated with cisplatin 60 mg/m2 and doxorubicin 60 mg/m2 on day 1 with a 3 or 4 week interval demonstrating response rates of 20 to 25% with and overall survival of 10 months.
Liposomal doxorubicin (LD) consists on doxorubicin encapsulated in liposomes that are composed of phosphatidylcholine and cholesterol. LD can extravasate into tumors with abnormal vascular endothelium but may not penetrate normal tissues lowering its toxicity and increasing its efficiency. Combining LD with cisplatin could be an effective new chemotherapy treatment for MPM.
Objective:
Increase chemotherapy response rates, progression free survival and overall survival in patients with MPM treated with LD plus cisplatin as a palliative treatment for MPM.
Methods:
We conducted a prospective analytical study between September 2006 and April 2009. Thirty patients with epithelial, sarcomatoid or biphasic histological confirmed diagnosis of MPM from the Instituto Nacional de Cancerología and the Instituto Nacional de Enfermedades Respiratorias were included to receive LD 60mg/m2 plus cisplatin 80 mg/m2 every 4 weeks for 6 cycles. During the first cycle of chemotherapy, a scintigraphic image study was done with LD labeled with Tc-99m (LD-Tc-99m). The imaging study (SPECT/CT) was done 1h after administration to evaluate biodistribution and accumulation of LD-Tc-99m in tumoral tissue. Patients were evaluated by a surgeon after 2 cycles of chemotherapy, if surgery was not possible, chemotherapy continued until tumor progression. Clinical and biochemical evaluations were obtained before chemotherapy administration. An axial computed tomography was requested before chemotherapy and every 2 months in the first 6 months and every 4 months during following 2 years. Treatment response was according to RECIST criteria and toxicity was evaluated with National Cancer Institute Common Toxicity Criteria version 3.0. The statistical analysis was made using SPSS v.10 software. For descriptive purposes, continuous variables were summarized as arithmetic means, medians, and standard deviations; and categorical variables with 95% confidence intervals. Disease-free progression and over-all survival were evaluated by Kapplan-Meier.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Pleural Mesothelioma
Keywords
Malignant pleural mesothelioma, Liposomal doxorubicin, Progression free survival, Patients who received LD 60mg/m2 plus cisplatin 80 mg/m2 every 4 weeks for 6 cycles, Patients with epithelial, sarcomatoid or biphasic histological confirmed diagnosis of MPM
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
31 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Liposomal doxorubicin
Arm Type
Experimental
Arm Description
Thirty patients with MPM who received liposomal doxorubicin 60mg/m2 plus cisplatin 80 mg/m2 every 4 weeks for 6 cycles.
Intervention Type
Drug
Intervention Name(s)
Liposomal doxorubicin
Intervention Description
Liposomal doxorubicin 60 mg/m2 every 4 weeks for 6 cycles.
Thirty patients with epithelial, sarcomatoid or biphasic histological confirmed diagnosis of MPM from the Instituto Nacional de Cancerología and the Instituto Nacional de Enfermedades Respiratorias were included to receive LD 60mg/m2 plus cisplatin 80 mg/m2 every 4 weeks for 6 cycles.
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
Cisplatin 80 mg/m2 every 4 weeks for 6 cycles.
Thirty patients with epithelial, sarcomatoid or biphasic histological confirmed diagnosis of MPM from the Instituto Nacional de Cancerología and the Instituto Nacional de Enfermedades Respiratorias were included to receive LD 60mg/m2 plus cisplatin 80 mg/m2 every 4 weeks for 6 cycles.
Primary Outcome Measure Information:
Title
Progression free survival
Time Frame
12 months
Title
Over-all survival
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with epithelial, sarcomatoid or biphasic histological confirmed diagnosis of MPM from the Instituto Nacional de Cancerología and the Instituto Nacional de Enfermedades Respiratorias
ECOG functional status 0 or 2
No renal function alteration (GFR >50%)
No hepatic function alteration
Leucocytes more than 2,000/mcl
Hemoglobin more than 10mg/dL
Platelets more than 100,000/mcl
Exclusion Criteria:
Patients who had received previous chemotherapy for MPM
Patients who do not accept the treatment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Enrique Estrada Lobato, M.D.
Organizational Affiliation
National Institute of Cancerología
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Luis Alberto Medina Velázquez, PhD.
Organizational Affiliation
Laboratorio de Enseñanza Virtual y Ciberpsicología. Facultad de Psicología. UNAM
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Elena Arechaga Ocampo, PhD.
Organizational Affiliation
National Institute of Cancerología
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Victoria López Rodrígez, Q.F.B.
Organizational Affiliation
National Institute of Cancerología
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Luisa Geraldine Villanueva Rodríguez, M.D
Organizational Affiliation
National Institute of Canerología
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Miguel Angel Ríos Trejo, M.D.
Organizational Affiliation
National Institute of Cancerología
Official's Role
Study Chair
Facility Information:
Facility Name
National Institute of Cancerología
City
Mexico city
State/Province
Distrito Federal
ZIP/Postal Code
14080
Country
Mexico
12. IPD Sharing Statement
Citations:
PubMed Identifier
22353806
Citation
Arrieta O, Medina LA, Estrada-Lobato E, Hernandez-Pedro N, Villanueva-Rodriguez G, Martinez-Barrera L, Macedo EO, Lopez-Rodriguez V, Motola-Kuba D, Corona-Cruz JF. First-line chemotherapy with liposomal doxorubicin plus cisplatin for patients with advanced malignant pleural mesothelioma: phase II trial. Br J Cancer. 2012 Mar 13;106(6):1027-32. doi: 10.1038/bjc.2012.44. Epub 2012 Feb 21.
Results Reference
derived
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Palliative Treatment With Liposomal Doxorubicin Plus Cisplatin for Patients With Malignant Pleural Mesothelioma
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