Mapatumumab, Cisplatin and Radiotherapy for Advanced Cervical Cancer
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.
Advanced Cervical Cancer
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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.|
- Phase 1b: safety and tolerability of mapatumumab in combination with cisplatin and radiotherapy Phase 2: efficacy of mapatumumab in combination with cisplatin and radiotherapy [ Time Frame: 5 months ] [ Designated as safety issue: Yes ]Phase 2: pathological complete response rate
- Disease free survival, overall survival [ Time Frame: From enrollment until recurrence of disease, from enrollment until death ] [ Designated as safety issue: No ]
- Apoptotic pathway biomarkers, PK parameters [ Time Frame: During the study, until 5 months after enrollment ] [ Designated as safety issue: No ]
|Study Start Date:||March 2010|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
|Experimental: Advanced cervical cancer patients||
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 45Radiation: 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.
|Contact: An KL Reyners, MD, PhD||+31 50 361 61 firstname.lastname@example.org|
|Contact: Elisabeth GE de Vries, MD, PhD||+31 50 361 61 email@example.com|
|University Medical Center Groningen||Recruiting|
|Groningen, Netherlands, 9700 RB|
|Contact: An KL Reyners, MD, PhD +31 50 361 6161 firstname.lastname@example.org|
|Contact: Elisabeth GE de Vries, MD, PhD +31 50 361 6161 email@example.com|
|Principal Investigator: An KL Reyners, PhD|
|Principal Investigator:||An KL Reyners, MD,PhD||University Medical Centre Groningen|