Brief Title
Phase II Study of Six Hours Low Dose Gemcitabine Plus Cisplatin in the Treatment for Advanced Pleural Mesothelioma
Official Title
Phase II Study of Six Hours, Low Dose Gemcitabine Plus Cisplatin in the Treatment for Advanced Pleural Mesothelioma.
Brief Summary
Malignant pleural mesothelioma (MPM) is a rare disease, but with a very high mortality. MPM
is frequently found in advanced stages. The standard treatment in advanced pleural
mesothelioma is cisplatin-based chemotherapy combined with pemetrexed/raltitrexed (phase III
studies showed its benefit in response and overall survival compared with cisplatin alone).
There are other active drugs such as liposomal doxorubicin and gemcitabine. Unfortunately,
cost is an important factor to consider in our population and standard treatments are very
expensive. Gemcitabine 250 mg infused over 6 hrs in combination with cisplatin, compared to
the standard administration of gemcitabine 1250 mg infusion of 30 minutes in NSCLC, combined
with cisplatin showed 75 mg shown in a study to be equally effective in treating cancer
non-small cell lung. A phase II study using this strategy for advanced MPM has shown
promising results. Gemcitabine administered in low dose in a six hour infusion may reduce
cost of treatment without altering the effectiveness.
Primary Objective.
-Evaluate the response of treatment with gemcitabine at a dose of 250 mg/m2SC in 6-hour
infusion combined with cisplatin in patients with unresectable malignant mesothelioma.
Secondary objectives.
- Evaluate toxicity of the combination of gemcitabine at a dose of 250 mg/m2 infused over
6 hours in with cisplatin in patients with unresectable malignant mesothelioma.
- Evaluate the progression free survival (PFS) and overall survival (OS) in patients with
unresectable MM treated with this combination.
Hypothesis:
Combination therapy of gemcitabine at a dose of 250 mg/m2 infusion of 6 hrs applied on day 1
and 8 combined with cisplatin 35 mg/m2SC applied on day 1 of 3 weeks cycles is a treatment
that provides similar results in responses when compared with previous studies with the same
combination therapy, but with a conventional administration (gemcitabine 1,250 mg in 30
minutes on days 1, 8 and 15).
Detailed Description
Malignant pleural mesothelioma is a rare disease, but with a high mortality. It usually
develops in people who were exposed to asbestos, with a latency period ranging from 20 to 40
years. Most of these patients present with advanced disease, which are considered
unresectable and combination chemotherapy is the treatment of choice. Currently the standard
treatment is the combination of pemetrexed with cispaltin, this treatment showed benefit in
overall survival and overall response rate in comparison with the treatment with cisplatin
alone. This standard chemotherapy in our country is difficult to access due to the costs of
the treatment and the poor economic situation of most of our patients. That's why determining
the effectiveness of other treatment options that have shown activity in this disease that
are less expensive, is of vital importance in our country. Phase I studies of gemcitabine
showed that the maximum tolerated dose varies with time of infusion, 250 mg/m2 is the maximum
tolerated dose when the infusion is carried out in 6 hours, as opposed to 1250 mg/m2 when
gemcitabine is administered in a conventional manner . A phase III study in NSCLC, which
compared the administration of gemcitabine infusion of 250 mg/m2 in 6 hours versus
conventional administration of 1,250 mg/m2 in 30 minutes showed that both treatments were
similar in efficacy and toxicity. The same group conducted a phase II study in unresectable
malignant pleural mesothelioma that was published recently with promising results. That is
why we decided to conduct a phase II study in patients with unresectable malignant pleural
mesothelioma with the idea of validating the results previously obtained and to study factors
and associated with resistance to chemotherapy as ERCC1, RPM1, thymidylate synthase.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Evaluate adverse effects to 250 mg/m2 infusion gemcitabine
Secondary Outcome
Progression Free Survival
Condition
Advanced Malignant Pleural Mesothelioma
Intervention
Gemcitabine
Study Arms / Comparison Groups
6 h infusion Gemcitabine and Cisplatin
Description: Gemcitabine 250 mg/m2 Cisplatin 30 mg/m2
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
26
Start Date
November 2010
Completion Date
December 2017
Primary Completion Date
December 2017
Eligibility Criteria
Inclusion Criteria:
- Histologic Diagnosis of Pleural Mesothelioma
- Multidisciplinary assessment and considered not candidate for resection.
- Karnofsky > = 70 or ECOG < 2
- Adequate Hematologic, renal and hepatic function.
Exclusion Criteria:
- Superior vena cava syndrome, severe bone pain or CNS metastasis
- Not candidate for chemotherapy (Poor functional status: ECOG > 2)
- The patient refuses to participate
Gender
All
Ages
18 Years - 75 Years
Accepts Healthy Volunteers
No
Contacts
Oscar Arrieta, MD, ,
Location Countries
Mexico
Location Countries
Mexico
Administrative Informations
NCT ID
NCT01869023
Organization ID
INCANOGAR2012-JA3
Responsible Party
Principal Investigator
Study Sponsor
Instituto Nacional de Cancerologia de Mexico
Collaborators
National Council of Science and Technology, Mexico
Study Sponsor
Oscar Arrieta, MD, Principal Investigator, Instituto de Cancerología
Verification Date
March 2017