Switch-Maintenance Gemcitabine After First-Line Chemotherapy In Patients With Malignant Pleural Mesothelioma

NCT ID: NCT05660616

Last Updated: 2024-08-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-01
• Study Completion Date: 2024-04-01

Brief Summary

Mesothelioma is an aggressive form of cancer. Treatments are available, but for many people, a cure isn't possible.

This thesis is to assess the efficacy and safety of switch-maintenance Gemcitabine in Mesothelioma patients after first line chemotherapy (Pemetrexed-Platinum)

Detailed Description

Malignant pleural mesothelioma is a rare but aggressive cancer of the pleural lining.

Malignant pleural mesothelioma accounted for 30,870 new cancer cases and 26,278 deaths worldwide in 2020.

In Egypt, Malignant pleural mesothelioma accounted for 337 new cases and 307 deaths in 2020.

Long-term exposure to asbestos is a well-established risk factor for Malignant pleural mesothelioma. It accounts for almost 80% of cases.

Malignant pleural mesothelioma is classified into three histologic subtypes: epithelioid, sarcomatoid, and biphasic. Epithelioid histology confers the most favorable prognosis and sarcomatoid the least.

The majority of patients with Malignant pleural mesothelioma present with breathlessness, chest pain or both. Other symptoms include fatigue, anorexia, weight loss, sweats and malaise.

Radiological imaging should be undertaken in all patients as it can provide valuable diagnostic and staging information. Further investigation of suspected Malignant pleural mesothelioma requires sampling of pleural fluid for biochemical and cytological examination. Biopsies are usually required to confirm the diagnosis and identify the histological sub-type.

Patients with Malignant pleural mesothelioma should be managed by an experienced multidisciplinary team. Treatment options include surgery, radiation therapy and chemotherapy.

Front line polychemotherapy is considered the standard of care, whereas single agent chemotherapy has shown limited efficacy with disappointing response rates.

A pivotal trial led to the establishment of Cisplatin and Pemetrexed as standard first line regimen for unresectable Malignant pleural mesothelioma.

A recent phase II trial from Cancer and Leukemia Group B showed that maintenance Pemetrexed after 4 to 6 cycles of doublet chemotherapy induction did not prolong progression free survival over placebo.

Adding Bevacizumab to first line platinum doublet resulted in an overall survival and progression free survival gain in the phase III French trial MAPS .Bevacizumab was continued as maintenance every three weeks following completion of six cycles of chemotherapy.

In a phase III trial NVALT 5 , Thalidomide versus active supportive care for maintenance in patients with malignant mesothelioma after first-line chemotherapy showed no benefit in time to progression.

First line Nivolumab plus Ipilimumab in phase III trial checkmate 743 provided significant and clinically meaningful improvements in overall survival versus standard of care chemotherapy.

Unfortunately, nearly all patients progress during or after first-line therapy, and no standard second line recommended treatments exist after platinum based regimen. Retreatment with pemetrexed, eventually associated with platinum compound, may be offered in patients who achieved durable disease control more than 6 months with first line chemotherapy.

Single agent chemotherapy with Vinorelbine or Gemcitabine is the preferred choice as second line treatment , mainly based on retrospective analyses or small phase II trials.

Conditions

Malignant Pleural Mesothelioma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Gemcitabine + supportive care

Administration of maintenance gemcitabine (1000 mg/m²) on days 1 and day 8, in cycles of 21 days plus supportive care.

Group Type: EXPERIMENTAL

Gemcitabine

Intervention Type: DRUG

The study includes patients with unresectable malignant pleural mesothelioma who received at least 4 cycles of first line platinum (Cisplatin or Carboplatin) and pemetrexed combination chemotherapy

• Response after first line treatment will be assessed by the modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1 for pleural mesothelioma.
• Patients will be randomized according to a (1:1) ratio to either Arm 1: Administration of maintenance gemcitabine (1000 mg/m²) on days 1 and day 8, in cycles of 21 days plus supportive care Arm 2 (control arm): best supportive care alone.
• Cases will be evaluated every cycle clinically and every three cycles radiologically with CTs.

supportive care

Intervention Type: OTHER

supportive care

supportive care

best supportive care alone.

Group Type: OTHER

supportive care

Intervention Type: OTHER

supportive care

Interventions

Gemcitabine

The study includes patients with unresectable malignant pleural mesothelioma who received at least 4 cycles of first line platinum (Cisplatin or Carboplatin) and pemetrexed combination chemotherapy

• Response after first line treatment will be assessed by the modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1 for pleural mesothelioma.
• Patients will be randomized according to a (1:1) ratio to either Arm 1: Administration of maintenance gemcitabine (1000 mg/m²) on days 1 and day 8, in cycles of 21 days plus supportive care Arm 2 (control arm): best supportive care alone.
• Cases will be evaluated every cycle clinically and every three cycles radiologically with CTs.

Intervention Type: DRUG

supportive care

supportive care

Intervention Type: OTHER

Other Intervention Names

Gemzar

Eligibility Criteria

Inclusion Criteria

• Being at least 18 years old
• Histologically or cytologically confirmed unresectable malignant pleural mesothelioma
• ECOG Performance status 0-2
• Completed at least four cycles of first line platinum (cisplatin or carboplatin) and pemetrexed combination chemotherapy before study entry
• No evidence of disease progression following first-line treatment based on radiological criteria.
• Adequate organ function is mandatory, defined as haemoglobin of at least 8.5 mg/dl, platelets of at least 100×10⁹ per L, and neutrophils of at least 1×10⁹/L.

Exclusion Criteria

• Progression of disease after first line
• Pregnant females
• ECOG Performance 3-4
• Patients with sarcomatoid mesothelioma
• Patients who are candidates for curative surgery

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ain Shams University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Abanoub Samir

Role: PRINCIPAL_INVESTIGATOR

Assistant Lecturer

Locations

Ain Shams University Hospital

Cairo, , Egypt

Countries

Egypt

References

Karam AS, Abdelwahab S, Ezz El Din MMA, Alorabi MO. A randomized comparative study on maintenance gemcitabine versus supportive care in pleural mesothelioma. Future Oncol. 2025 Jul;21(17):2203-2213. doi: 10.1080/14796694.2025.2516412. Epub 2025 Jun 12.

Reference Type: DERIVED

PMID: 40501447 (View on PubMed)

Other Identifiers

SMGFM

Identifier Type: -

Identifier Source: org_study_id