TN-TC11G (THC+CBD) Combination With Temozolomide and Radiotherapy in Patients With Newly-diagnosed Glioblastoma (GEINOCANN)
|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: NCT03529448|
Recruitment Status : Not yet recruiting
First Posted : May 18, 2018
Last Update Posted : May 31, 2019
Glioblastoma is the primary brain tumour with the worst prognosis: median survival is only 12 months despite the use of the most advanced treatments. In the past 10 years, survival in the treatment of this disease has not advanced significantly, with the postoperative standard being the administration of chemoradiotherapy with temozolomide, followed by 6 cycles of sequential chemotherapy with temozolomide.
Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have shown a clear synergistic antitumour effect with temozolomide and radiotherapy in preclinical glioma models. THC and CBD have a wide variety of biological effects by binding with and activating the type 1 and type 2 cannabinoid receptors (CB1 expressed in certain neuronal areas of the brain and CB2 expressed in the immune system and in glial cells). The activation of these receptors initiates a signalling pathway, called the endoplasmic reticulum stress response, which generates tumour cell autophagy by activating TRB3.
Given these data, the Spanish Group for Neuro-oncology (GEINO) proposes developing a phase Ib, open-label, multicenter, intrapatient dose-escalation clinical trial to assess the safety profile of the THC+CBD combination at a 1:1 ratio, adding temozolomide and radiotherapy in patients with newly-diagnosed glioblastoma.
The number of patients to be recruited is 30 over 6 months at 8 sites specialising in neuro-oncology.
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma||Drug: TN-TC11G Drug: Temozolomide Oral Product Radiation: Radiotherapy||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||Phase Ib, intra-patient dose escalation trial.|
|Masking:||None (Open Label)|
|Official Title:||Phase Ib, Open-label, Multicenter, Intrapatient Dose-escalation Clinical Trial to Assess the Safety Profile of the TN-TC11G (THC+CBD) Combination With Temozolomide and Radiotherapy in Patients With Newly-diagnosed Glioblastoma|
|Estimated Study Start Date :||July 2019|
|Estimated Primary Completion Date :||June 2020|
|Estimated Study Completion Date :||June 2020|
Experimental: TN-TC11G, radiotherapy and Temozolomide Oral Product
During Phase Ib, Four to seven weeks after surgical diagnosis, concurrent with radiotherapy (STUPP)
+ temozolomide (75mg/m2/day for 42 days) +TN-TC11G will be evaluated. During radiation therapy, temozolomide and TN-TC11G will be administered. This last, as the dose that have been selected previously, based on dose-titration period. Patient specific dose will remain until progresion of disease, unacceptable toxicity, non-compliance, consent withdrawal up to 2 years.
TN-TC11G dose will be gradually increased as follows:
Week 1: TN-TC11G: 0-0-5 mg (THC 5 mg + CBD 5 mg; in the mornings, 90 minutes after breakfast; in the afternoons, 90 minutes after lunch; in the evenings, 90 minutes after dinner).
Week 2: TN-TC11G: 5-0-5 mg Week 3: TN-TC11G: 5-5-5 mg Week 4: TN-TC11G: 5-5-10 mg Week 5: TN-TC11G: 5-5-15 mg Week 6: TN-TC11G: 10-10-15 mg Week 7: TN-TC11G: 10-10-20 mg. Week 8: TN-TC11G: 15-15-30 mg Week 9: TN-TC11G: 20-20-40 mg TN-TC11G will be administered daily at the relevant dose level according to the individual titration performed in the first 9 weeks of treatment. If there is any dose reduction, the reduced dose must be administered.
Drug: Temozolomide Oral Product
During RT, patients will receive Temozolomide (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.
Other Name: Temozolomide
All the patients will receive the Stupp regimen. The radiotherapy (RT) treatment will be administered in fractions of 1.8-2.0 Gy/day delivered 5 days/week to a total dose of 58-60 Gy. Radiotherapy will be delivered to the gross tumor volume with a 2-3 cm margin for the clinical target volume.
Other Name: STUPP
- THC-CBD Maximum tolerated dose [ Time Frame: 9 weeks ]After intra-patient dose escalation period, recommended dose of Glasdegib administeres with temozolamide during and after RT.
- Incidence of Treatment-Emergent Adverse Events [ Time Frame: 12 months ]Type and number or adverse events reported during THC-CBD treatment, based on the CTCAE reference criteria.
- Antitumor activity of THC-CBD combination with temozolamide and radiotherapy [ Time Frame: 12 months ]Based on the tumor response in patients with measurable disease, after comparison of baseline characteristics and follow-up evaluations
- Overall survival [ Time Frame: 12 months ]Time between the start of treatment to death
- Progression free survival [ Time Frame: 12 months ]Time between the start of treatment and progression of disease
- Expression of Midkine [ Time Frame: 12 months ]Correlation of expression of midkine in peripheral blood and response to the experimental treatment.
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): NCT03529448
|Contact: Federico Nepote||+34 93 434 44 firstname.lastname@example.org|
|Contact: Verónica Roca||+34 93 434 44 email@example.com|
|Institut Català d'Oncología L'Hospitalet||Not yet recruiting|
|L'Hospitalet de Llobregat, Barcelona, Spain, 08908|
|Contact: Miguel Gil, M.D. firstname.lastname@example.org|
|Principal Investigator: Miguel Gil, M.D.|
|Hospital Universitario Son Espases|
|Palma de Mallorca, Mallorca, Spain|
|Consorcio Hospitalario Provincial de Castellón||Not yet recruiting|
|Castelló, Valencia, Spain, 12002|
|Contact: Ramón de las Peñas, M.D. email@example.com|
|Principal Investigator: Ramón de las Peñas, M.D.|
|Hospital del Mar||Not yet recruiting|
|Barcelona, Spain, 08003|
|Contact: Maria Martinez, M.D. firstname.lastname@example.org|
|Principal Investigator: María Martínez, M.D.|
|Complejo Hospitalario Regional Virgen de las Nieves||Not yet recruiting|
|Granada, Spain, 18004|
|Contact: Raquel Luque, MD email@example.com|
|Principal Investigator: Raquel Luque, M.D.|
|Hospital Universitario 12 de Octubre||Not yet recruiting|
|Madrid, Spain, 28041|
|Contact: Juan Sepúlveda firstname.lastname@example.org|
|Principal Investigator: Juan Sepúlveda, M.D.|
|Hospital Regional Universitario de Malaga|
|Hospital Clínico Universitario de Salamanca||Not yet recruiting|
|Salamanca, Spain, 37007|
|Contact: Luis Miguel Navarro, M.D. email@example.com|
|Principal Investigator: Luis Miguel Navarro, M.D.|
|Principal Investigator:||Manuel Benavides, M.D., Ph.D.||Hospital Universitario y Regional de Málaga y Virgen de la Victoria|