TN-TC11G (THC+CBD) Combination With Temozolomide and Radiotherapy in Patients With Newly-diagnosed Glioblastoma

NCT03529448 | Completed Phase 1 DMC

• 2 other identifiers: GEINO-16012016-003216-12
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Glioblastoma

Keywords

Glioblastoma

Outcome Measures

Primary Outcomes (2)

• THC-CBD Maximum tolerated dose

  After intra-patient dose escalation period, recommended dose of Glasdegib administeres with temozolamide during and after RT.

  9 weeks

• Incidence of Treatment-Emergent Adverse Events

  Type and number or adverse events reported during THC-CBD treatment, based on the CTCAE reference criteria.

  12 months

Secondary Outcomes (4)

• Antitumor activity of THC-CBD combination with temozolamide and radiotherapy

  12 months

• Overall survival

  12 months

• Progression free survival

  12 months

• Expression of Midkine

  12 months

Study Arms (1)

TN-TC11G, radiotherapy and Temozolomide Oral Product

EXPERIMENTAL

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.

Drug: TN-TC11G; Drug: Temozolomide Oral Product; Radiation: Radiotherapy

Interventions

TN-TC11G DRUG

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.

TN-TC11G, radiotherapy and Temozolomide Oral Product

Temozolomide Oral Product DRUG

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.

Also known as: Temozolomide

TN-TC11G, radiotherapy and Temozolomide Oral Product

Radiotherapy RADIATION

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.

Also known as: STUPP

TN-TC11G, radiotherapy and Temozolomide Oral Product

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to understand and sign the informed consent document
• Men or women ≥18 years and ≤70 years
• Newly-diagnosed GB confirmed by biopsy or by resection in the 4-7 weeks before being registered in the trial.
• Patients must have at least 15 slides without staining or a tissue block (frozen or paraffin-embedded) available from a previous biopsy or surgery (tumour sample previously archived).
• Karnofsky Index ≥60%.
• Adequate bone marrow reserve: haemoglobin ≥10 g/dL, WBC \>3,000/mcL, absolute neutrophil count (ANC) ≥1,500 cells/μL, platelets ≥100,000 cells/μL.
• Adequate liver function: Bilirubin \<1.5 times the upper limit of normal (ULN); AST ≤2.5 x ULN
• Creatinine clearance \>60 ml/min/1.73 m2.

You may not qualify if:

• Presence of extracranial metastatic disease.
• Any previous treatment for glioblastoma.
• Patients who have had a Gliadel implant in the surgery.
• Previous abuse of cannabinoids.
• Presence of any clinically significant gastrointestinal abnormality that may affect the intake, transit or absorption of the study drug, such as the inability to take medication in the form of oral tablets or solution.
• Presence of any psychiatric or cognitive impairment that limits understanding or the signing of the informed consent and/or compromises compliance with the requirements of this protocol.
• Significant or uncontrolled cardiovascular disease, including: 1. Myocardial infarction in the previous 12 months. 2. Uncontrolled angina in the previous 6 months. 3. Congestive heart failure in the previous 6 months. 4. Diagnosed or suspected congenital long QT syndrome. 5. History of ventricular arrhythmias of any clinically significant type (such as ventricular tachycardia, ventricular fibrillation or torsades de pointes). 6. QTc prolongation on an electrocardiogram prior to entry (\>470 ms). 7. History of second- or third-degree heart block (these patients may be eligible if they carry pacemakers). 8. Heart rate \<50/min on the baseline electrocardiogram. 9. Uncontrolled hypertension
• Any patient with a history of significant cardiovascular disease, even if it is currently controlled, or who presents signs or symptoms that suggest impaired left ventricular function according to the investigator should have an assessment of left ventricular ejection fraction (LVEF) by ECCO or MUGA. If the LVEF in these circumstances is below the site's lower limit of normality or less than 50%, the patient will not be eligible.
• History of any cancer, except in the following circumstances: Patients with a history of other malignancies are eligible if they have been disease-free for at least the last 3 years and if, in the investigator's opinion, there is a low risk of disease recurrence. People with the following cancers are eligible, even if they have been diagnosed and treated in the past 3 years: cervical carcinoma in situ and basal cell carcinoma.
• Patients will not be eligible if there is evidence of another cancer that required therapy other than surgery in the past 3 years.

Sponsors & Collaborators

• Grupo Español de Investigación en Neurooncología: lead
• Medical Cannabis Bike Tour: collaborator
• Voices Against Brain Cancer: collaborator
• Tilray: collaborator

Study Sites (8)

Hospital Universitario Virgen del Rocío

Seville, Andalusia, 41013, Spain

Location

Institut Català d'Oncología L'Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital Universitario Son Espases

Palma de Mallorca, Mallorca, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Complejo Hospitalario Regional Virgen de las Nieves

Granada, 18004, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Regional Universitario de Malaga

Málaga, Spain

Location

Hospital Clínico Universitario de Salamanca

Salamanca, 37007, Spain

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Temozolomide; Radiotherapy

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics

Study Officials

• Manuel Benavides, M.D., Ph.D.

  Hospital Universitario y Regional de Málaga y Virgen de la Victoria

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase Ib, intra-patient dose escalation trial.

Study Record Dates

• First Submitted: April 23, 2018
• First Posted: May 18, 2018
• Study Start: August 18, 2023
• Primary Completion: November 13, 2025
• Study Completion: November 13, 2025
• Last Updated: February 12, 2026

Record last verified: 2026-02

Locations

ES (8)