NCT01088347

Mapatumumab, Cisplatin and Radiotherapy for Advanced Cervical Cancer

A Phase 1b/2 Study With the Agonistic TRAIL-R1 Antibody, Mapatumumab, in Combination With Cisplatin and Radiotherapy as a First Line Therapy in Patients With Advanced Cervical Cancer.

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 9 (actual)
• Sponsor: University Medical Center Groningen · Academic / Other
• Sex: Female
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

Chemoradiotherapy has become the standard of care for women with locally advanced cervical cancer. The available data support a 30 to 50% reduction in the risk of death from cervical cancer for women with locally advanced disease undergoing radiotherapy (RT) and concomitant cisplatin-based chemotherapy compared to RT alone. Despite the fact that this is currently the best treatment of locally advanced cervical cancer, 5-year overall survival is still only 52%. The fully human, agonist monoclonal antibody mapatumumab binds to the Tumor necrosis factor-Related Apoptosis-Inducing Ligand Receptor 1 (TRAIL-R1, DR4) and induces cytotoxicity in multiple tumor cell lines in vitro and in vivo. In multiple phase I and phase II studies, mapatumumab appeared to be safe both as single agent and in combination with chemotherapy, including cisplatin. In cervical cancer cell lines, mapatumumab induced apoptosis in 51% of the cells. Mapatumumab in combination with irradiation increased apoptosis to 83%. In this phase 1b/2 study, the investigators will evaluate the safety, tolerability and efficacy of mapatumumab in combination with cisplatin and radiotherapy in patients with locally advanced cervical cancer.

Conditions

• Advanced Cervical Cancer

Interventions

Type	Name	Description
DRUG	mapatumumab	Mapatumumab (10 or 30 mg/kg) intravenously on days 1, 22, and 45. In phase 2 the MTD established in phase 1 will be used.
DRUG	cisplatin	Cisplatin 40 mg/m2 intravenously on days 8, 15, 22, 29, 36, and 45
RADIATION	radiotherapy	Radiotherapy: a total dose of 45 Gy will be given in fractions of 1.8 Gy, five fractions per week (days 8-12, 15-19, 22-26, 29-33, and 36-40), by external beam irradiation by photon beam of at least 6 MV. After completing the five weeks of external beam irradiation, evaluation will take place to determine whether the boost can be given by brachytherapy. If brachytherapy is not feasible, the boost will be given by external beam irradiation to a total dose of 70.2 Gy in fractions of 1.8 Gy.

Timeline

• Start date: 2010-03-01
• Primary completion: 2014-03-01
• Completion: 2014-03-01
• First posted: 2010-03-17
• Last updated: 2024-04-19

Locations

1 site across 1 country: Netherlands