Pembrolizumab and Vorinostat Combined With Temozolomide for Newly Diagnosed Glioblastoma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03426891|
Recruitment Status : Recruiting
First Posted : February 8, 2018
Last Update Posted : September 3, 2018
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma Brain Tumor GBM||Drug: Pembrolizumab Drug: Vorinostat Drug: Temozolomide Radiation: Radiotherapy||Phase 1|
There are 2 parts to this study:
Part 1 (dose escalation) and Part 2 (dose expansion). The main purpose of Part 1 is Dose-Escalation. "Dose-Escalation" means that different dose levels will be tested at different times during the study to find the best dose level that is safe and well tolerated in participants. In this study investigators will determine the best dose of Vorinostat that can be given with pembrolizumab, chemotherapy and radiotherapy. The dose of temozolomide and radiotherapy will be the same as standard treatment.
Part 2 (Dose Expansion), all participants will receive the same dose of vorinostat with pembrolizumab, chemotherapy and radiotherapy.
Maintenance Phase: During the maintenance phase, participants will receive Temozolomide (for the first 6 months), vorinostat (for 12 months), and pembrolizumab (for 12 months).
|Study Type :||Interventional|
|Estimated Enrollment :||32 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Trial of Pembrolizumab and Vorinostat Combined With Temozolomide and Radiation Therapy for Newly Diagnosed Glioblastoma|
|Actual Study Start Date :||March 16, 2018|
|Estimated Primary Completion Date :||April 2021|
|Estimated Study Completion Date :||April 2022|
Experimental: Combination Therapy
Pembrolizumab and Vorinostat Combined with Temozolomide and Radiotherapy. There are two parts to this study: Part 1 (dose escalation) and Part 2 (dose expansion). Dose Expansion: Twenty participants will be treated with vorinostat at the maximum tolerated dose (MTD) from dose escalation phase, pembrolizumab, temozolomide and radiation. During the maintenance phase, participants will receive Temozolomide (for the first 6 months), vorinostat (for 12 months), and pembrolizumab (for 12 months).
200 mg intravenously (IV) every 3 weeks. The dose of pembrolizumab will remain the same throughout study treatment. During the maintenance phase, participants will receive pembrolizumab (for 12 months).
Dose Escalation Level 1:vorinostat 200 mg/day by mouth on day 1-5 every week during radiotherapy, starting on first day of radiotherapy; and 300 mg/day 1 week on 1 week off after radiotherapy. Dose Escalation Level 2: vorinostat 300 mg/day by mouth on days 1-5 every week during radiotherapy, starting on first day of radiotherapy; and 400 mg/day 1 week on 1 week off after radiotherapy. Dose Expansion:all participants will receive the same dose of vorinostat that was determined to be most tolerated dose. During the maintenance phase, participants will receive vorinostat (for 12 months).
All participants will receive standard Temozolomide: Temozolomide (chemotherapy) 75 mg/m^2/day by mouth administered during the course of radiotherapy. Temozolomide will be administered continuously from Day 1 of radiotherapy to the last day of radiation. Maintenance Phase: temozolomide will start 4 weeks (+/- 3 days) after last dose of radiotherapy and will continue for 6 cycles post radiotherapy (150-200 mg/m^2/day, days 1-5 every 4 weeks) as per standard of care. During the maintenance phase, participants will receive Temozolomide (for the first 6 months).
All participants will receive standard radiotherapy: a total dose of 60 Gy administered in daily doses of 2 Gy, typically on a 5 days on / 2 days off schedule over 6 - 7 weeks.
Other Name: radiation therapy
- Maximum Tolerated Dose (MTD) [ Time Frame: 12 weeks ]The maximum tolerated dose (MTD)/recommended dose expansion dose of vorinostat given in combination with pembrolizumab, temozolomide, and radiotherapy in patients with newly diagnosed glioblastoma. Toxicities will be graded in severity according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 for toxicity categories as outlined in the study protocol.
- Overall Survival (OS) [ Time Frame: Up to 24 months ]Median overall survival time, 95% confidence survival. OS: Time from randomization until death from any cause.
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): NCT03426891
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute||Recruiting|
|Tampa, Florida, United States, 33612|
|Contact: Melissa Wicklund 813-745-3620 firstname.lastname@example.org|
|Contact: Solmaz Sahebjam, M.D. 813-745-6101 email@example.com|
|Principal Investigator:||Solmaz Sahebjam, M.D.||H. Lee Moffitt Cancer Center and Research Institute|