NCT03466450

Glasdegib (PF-04449913) With Temozolomide Newly Diagnosed Glioblastoma

Phase Ib/II Multicentric Study Combining Glasdegib (PF-04449913) With Temozolomide in Patients With Newly Diagnosed Glioblastoma, Safety and Preliminary Efficacy for the Combination

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 75 (actual)
• Sponsor: Grupo Español de Investigación en Neurooncología · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

Glioblastomas (GBMs) are the most common malignant primary brain tumors. Despite multimodality aggressive therapies (surgery followed by chemoradiotherapy based on TMZ and adjuvant TMZ), median overall survival is only 12 to 15 months. This dramatic behavior is mainly due to the high invasiveness and proliferation rate of GBM. In addition, GBM exhibits a high resistance to standard chemotherapy and radiotherapy. Current strategies for the treatment of GBM are only palliative, and include surgical resection (which is frequently incomplete due to the proximity of the tumour to vital brain structures) and focal radiotherapy. A large number of chemotherapeutic agents (e.g. alkylating agents such as TMZ and nitrosoureas such as carmustine) have also been tested, but they display limited efficacy. The current gold standard first line treatment for glioma for patients less than 70 years old includes radiation and concurrent TMZ followed by adjuvant TMZ (i.e., the "Stupp regimen"). However, results are disappointing and there is an unmet medical need of new drugs in this setting. Glasdegib (SHH pathway inhibitor) is a rational therapeutic agent for patients with newly diagnosed Glioblastoma since inhibits SHH pathway interfering with cancer stem cells and endothelial migration.

Conditions

• Glioblastoma

Interventions

Type	Name	Description
DRUG	PF-04449913	Glasdegib (3 dose levels will be evaluated: 100mg QD, 150mg QD and 200mg QD, or 75-50mg) will be administered: During concurrent phase concomitantly with radiation and Extended to the resting period (glasdegib will not be stopped in the 4 weeks of radiotherapy resting period). During adjuvant therapy with Temozolomide Oral Capsule. Additional treatment with glasdegib beyond 6 sequential TMZ cycles will continue until progression, unacceptable toxicity, non-compliance, consent withdrawal and/or 2 years of glasdegib administration.
DRUG	Temozolomide Oral Capsule	During RT, patients will receive Temozolamide (TMZ). All patients will be given TMZ at 75 mg/m2 /d concurrently with RT for a maximum of 42 days. At 4 weeks after RT completion, patients will start taking TMZ at 150 mg/m2/d for the first 5 days of a 28-day cycle. If first cycle is well tolerated, patients will receive TMZ at 200 mg/m2/d for the first 5 days of every subsequent 28-day cycle for another 5 cycles.

Timeline

• Start date: 2018-03-15
• Primary completion: 2023-11-29
• Completion: 2023-11-29
• First posted: 2018-03-15
• Last updated: 2024-03-28

Locations

8 sites across 1 country: Spain