Glasdegib (PF-04449913) With Temozolomide Newly Diagnosed Glioblastoma (GEINOGLAS)
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|ClinicalTrials.gov Identifier: NCT03466450|
Recruitment Status : Recruiting
First Posted : March 15, 2018
Last Update Posted : May 31, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma||Drug: PF-04449913 Drug: Temozolomide Oral Capsule||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||75 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||Phase Ib/II, multicentric, non-randomized, open label|
|Masking:||None (Open Label)|
|Official Title:||Phase Ib/II Multicentric Study Combining Glasdegib (PF-04449913) With Temozolomide in Patients With Newly Diagnosed Glioblastoma, Safety and Preliminary Efficacy for the Combination|
|Actual Study Start Date :||March 15, 2018|
|Estimated Primary Completion Date :||December 2020|
|Estimated Study Completion Date :||March 2021|
Experimental: Glasdegib and Temozolomide Oral Capsule
During Phase Ib, Four to six weeks after surgical diagnosis, concurrent with radiotherapy (STUPP) + temozolomide (75mg/m2/day for 42 days) + PF-04449913 (Glasdegib) (3 dose levels will be evaluated: 100mg QD, 150mg QD and 200mg QD, or 75-50mg) will be administered.
During Phase II, Radiation therapy, temozolomide and glasdegib will be administered. This last, as the dose that have been selected previously, based on the Phase Ib results. Glasdegib ( PF-04449913) recommended dose until progresion of disease, unacceptable toxicity, non-compliance, consent withdrawal up to 2 years.
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.
Other Name: Glasdegib
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.
- Glasdegib Dose [ Time Frame: 12 weeks ]For Phase Ib, The recommended dose for phase 2 (RDP2) of Glasdegib administered with temozolomide during and after RT.
- Overall survival [ Time Frame: 15 months ]For Phase II, time between the start of treatment to death
- Progression Free Survival [ Time Frame: 24 months ]Time between the start of treatment and progression of disease
- Adverse events (safety) [ Time Frame: 24 months ]Based on the number and type of adverse events reported since the start of treatment and throughout the study period.
- Response to treatment [ Time Frame: 24 months ]Based on RANO criteria
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03466450
|Contact: Federico Nepote||+34 93 434 44 email@example.com|
|Contact: Verónica Roca||+34 93 434 44 firstname.lastname@example.org|
|Institut Catalá de Oncología Badalona/Hospital Germans Trias i Pujol||Recruiting|
|Badalona, Barcelona, Spain, 08916|
|Contact: Carmen Balañá, M.D. +34 972 22 58 34 email@example.com|
|Principal Investigator: Carmen Balañá, M.D.|
|Institut Catalá de Oncología Girona/Hospital Universitari Dr. Josep Trueta||Recruiting|
|Girona, Spain, 17007|
|Contact: Sonia del Barco, M.D. +34 972 22 58 34 ext 7977 firstname.lastname@example.org|
|Principal Investigator: Sonia del Barco, M.D.|
|Hospital Universitario Ramón y Cajal||Recruiting|
|Contact: Mª Ángeles Vaz 91 336 80 00 ext 7977 email@example.com|
|Principal Investigator: Mª Ángeles Vaz, M.D.|
|Hospital Universitario y Politécnico La Fe||Recruiting|
|Valencia, Spain, 46009|
|Contact: José Muñoz Langa, M.D. +34 934344412 firstname.lastname@example.org|
|Principal Investigator: José Muñoz Langa, M.D.|
|Study Chair:||María Angeles Vaz, M.D.||Hospital Universitario Ramón y Cajal|