Gemcitabine as Maintenance Treatment of Diffuse Pleural Mesothelioma: Randomized Phase II Study
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- National Cancer Institute, Egypt
- Enrollment
- 64
- Locations
- 1
- Primary Endpoint
- Progression-Free Survival (PFS)
Overview
Brief Summary
What is this study about?
This study looks at whether continuing chemotherapy with a drug called gemcitabine after initial treatment can help patients with diffuse pleural mesothelioma keep their cancer under control for a longer time.
Diffuse pleural mesothelioma is a rare and aggressive cancer that affects the lining of the lungs. Even after standard chemotherapy, the disease often comes back quickly. Doctors are therefore looking for maintenance treatments that may delay cancer progression.
What does this mean for patients and families?
Gemcitabine maintenance treatment may help delay cancer progression It does not clearly extend overall life expectancy Side effects are common and should be carefully discussed with the treating oncologist
Treatment decisions should consider:
Patient performance status Symptoms Personal preferences and quality of life
What does this mean for health care providers?
Gemcitabine maintenance may be an option for:
Fit patients Those who responded to first-line chemotherapy Careful patient selection is essential Monitoring for hematologic toxicity is required Further larger studies are needed to confirm survival benefit
Detailed Description
Diffuse pleural mesothelioma (DPM) is an aggressive malignancy with limited therapeutic options and a high risk of early disease progression despite initial response to platinum-based chemotherapy. Although first-line systemic treatment can achieve disease control in a subset of patients, most will experience relapse within a short time interval. Strategies aimed at maintaining disease control after completion of induction chemotherapy are therefore of clinical interest.
Maintenance therapy using a non-cross-resistant cytotoxic agent represents a potential approach to delay tumor progression while preserving acceptable tolerability. Gemcitabine is an antimetabolite chemotherapeutic agent with documented activity in mesothelioma and a manageable safety profile. Its use as switch-maintenance therapy following platinum-based induction treatment may provide continued suppression of tumor growth without overlapping toxicity.
This randomized, open-label, phase II study was designed to evaluate whether gemcitabine maintenance therapy improves progression-free survival compared with best supportive care alone in patients with unresectable DPM who achieved complete response, partial response, or stable disease after first-line chemotherapy. Patients were randomized in a 1:1 ratio to receive either gemcitabine maintenance therapy plus best supportive care or best supportive care alone.
The study also explores the impact of maintenance therapy on overall survival and evaluates treatment-related toxicity. In addition, clinical and pathological factors such as performance status and histological subtype are assessed for their prognostic relevance. The results of this trial aim to inform clinical decision-making regarding post-induction management strategies in unresectable diffuse pleural mesothelioma.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Masking Description
This is an open-label study. No masking was applied to participants, investigators, or outcome assessors due to the nature of the intervention.
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age ≥ 18 years
- •Histologically confirmed unresectable diffuse pleural mesothelioma
- •Complete response, partial response, or stable disease after 4-6 cycles of first-line platinum-based chemotherapy, according to modified RECIST (mRECIST) criteria
- •Last dose of first-line chemotherapy administered within 60 days prior to randomization
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Life expectancy of at least 12 weeks
- •Adequate bone marrow function
- •Adequate hepatic function
- •Adequate renal function
- •Ability to provide written informed consent
Exclusion Criteria
- •Prior extra-pleural pneumonectomy
- •Evidence of active brain or leptomeningeal metastases
- •Weight loss \>10% within 6 weeks prior to enrollment
- •Clinically significant ascites
- •Known hypersensitivity or intolerance to gemcitabine
- •Receipt of non-palliative radiotherapy within 3 weeks before initiation of study treatment
Arms & Interventions
Gemcitabine Maintenance Therapy
Patients received gemcitabine as maintenance therapy in addition to best supportive care following response or stable disease after first-line platinum-based chemotherapy.
Intervention: Gemcitabine (1000 mg/m2) (Drug)
Best Supportive Care
Patients received best supportive care alone, including symptom control and palliative measures, without active anti-cancer maintenance chemotherapy.
Outcomes
Primary Outcomes
Progression-Free Survival (PFS)
Time Frame: From randomization until disease progression or death from any cause, up to 36 months
Progression-free survival is defined as the time from randomization to the first documented disease progression according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) for pleural mesothelioma or death from any cause, whichever occurs first.
Secondary Outcomes
- Objective Response Rate (ORR)(Assessed every 8 weeks from randomization until disease progression, up to 24 months)
- Treatment-Related Toxicity(From first dose of study treatment until 30 days after treatment discontinuation)
- Prognostic Factors Associated With Progression-Free and Overall Survival(From randomization until death or end of follow-up, up to 36 months)
Investigators
Mohamed emam salah
lecturer of Medical Oncology
National Cancer Institute, Egypt