Neoplasms

All Conditions

Rare Diseases

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Temozolomide

Antineoplastic Agents, Alkylating

Alkylating Agents

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.

TN-TC11G

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.

Temozolomide Oral Product

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.

Radiotherapy

Federico Nepote

Verónica Roca

Investigator Selected by Sponsor

Principal Investigator Selected by Sponsor

Manuel Benavides, M.D., Ph.D.

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.

Phase Ib, intra-patient dose escalation trial.

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

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

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

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

Based on the tumor response in patients with measurable disease, after comparison of baseline characteristics and follow-up evaluations

Time between the start of treatment to death

Time between the start of treatment and progression of disease

Correlation of expression of midkine in peripheral blood and response to the experimental treatment.

Medical Cannabis Bike Tour

Voices Against Brain Cancer

Tilray

Grupo Español de Investigación en Neurooncología

Blood and Lymph Conditions

Immune System Diseases

Lymphopenia

Patients randomized to 40 Gy in 15 fractions will receive 75 mg/m\^2 temozolomide per day for 15 days starting the first day of radiotherapy. This treatment will be followed by standard monthly 5 day cycles at 150 mg/m\^2 for upto 1 year.

Patients randomized to 25 Gy in 5 fractions will receive 150 mg/m\^2 temozolomide per day for 5 days starting the first day of radiotherapy. This treatment will be followed by standard monthly 5 day cycles at 150 mg/m\^2 for upto 1 year.

Radiation Therapy

Oral Temozolomide (150mg/m\^2 or 75 mg/m\^2)

John Flickinger, MD

This is a prospective, randomized, open-label, exploratory trial of temozolomide-based chemo-radiotherapy which compares two widely used established radiation schedules with either 40 Gy in 15 fractions or 25 Gy in 5 fractions with concurrent temozolomide for both schedules in patients with glioblastoma.

All patients in the study will receive usual care with short-course radiotherapy (RT) and TMZ-chemo pills.

There are three phases of treatment in this study: the Chemo-radiation Phase, the Adjuvant Phase, and the Follow-Up Phase.

Twenty-eight or fewer days prior to starting the Chemo-radiation Phase, patients will have a baseline Magnetic Resonance Imaging (MRI) scan.

Chemo-radiation Phase: In this, patient will be assigned to either a one week or a three week treatment group with radiation treatments given approximately 5 days a week as directed by the study doctor. During this time they will also take TMZ-chemo orally (by mouth) once a day on every evening including weekends starting the evening of the day that you start radiotherapy. Once radiation is completed, you will stop taking TMZ-chemo for approximately 4 weeks before going to the next phase.

Radiation therapy: Patients will be randomized between standard radiation treatment at UPMC Radiation Oncology facilities included in this protocol with either 40 Gy in 15 fractions or 25 Gy in 5 fractions, using 6 to 23 MV x-rays along with concurrent temozolomide chemotherapy for both treatment schedules.

* Clinical treatment volumes (CTV) will include all contrast enhancing tumor plus 1.7cm expansion into brain tissue (not crossing the tentorium) and all T2 FLAIR hyperintensity plus 7mm expansion into brain tissue (not crossing the tentorium). A planning target volume (PTV) expansion of 3mm will be then added to the CTV. No additional exclusion of brainstem or optic nerves is required as both treatment schedules are within tolerance.
* Treatment may be delivered with either 3D-conformal or intensity modulated radiotherapy (IMRT) techniques.

Adjuvant Phase: In the Adjuvant Phase, you will receive standard monthly 5 day cycles of TMZ-chemo at 150 mg/m\^2 per day for up to 1 year.

Chemotherapy: Patient will receive concurrent temozolomide throughout radiation therapy, followed by standard monthly 5 day cycles for up to 1 year. Patients randomized to 25 Gy in 5 fractions will receive 150 mg/m\^2 of temozolomide per day for 5 days starting first day of radiotherapy. Patients randomized to 40 Gy in 15 fractions will receive 75 mg/m2 of temozolomide per day for 19 days starting first day of radiotherapy. Patients will be appropriately pre-medicated with anti-nausea medication, prior to taking temozolomide. All patients will also receive prophylactic treatment for pneumocystis pneumonia with Bactrim or other alternative antibiotics if allergic.

Follow-up Interval: Procedures performed to evaluate the safety and effectiveness of the study procedures are called "monitoring" or "follow-up" procedures. Subject participants will not be scheduled for any additional follow-up visits for this study than they would normally have if they were not in this study. Radiation Oncologists and Neuro-Oncologists usually see their patients one month after the first chemo-radiotherapy cycle before starting the next cycle of chemotherapy. After that Neuro-Oncologists and Radiation Oncologists will see the patients every 1-3 months.

Short Course Chemo-Radiation Therapy for Patients With Newly Diagnosed Glioblastoma

Short Course Chemo-Radiation Therapy for Patients With Newly Diagnosed Glioblastoma: Comparison of Two Established Schedules

The length of time from the start of treatment that patients remain alive.

Differences in absolute lymphocyte count (total lymphocyte count \<800 - 500/mm\^3 \<0.8 - 0.5 x 10\^9 /L) / total # patients, during treatment.

The length of time during and after the treatment that a patient lives without worsening disease per Response Assessment in Neuro-Oncology (RANO) criteria. Disease progression per RANO: (any of the following): ≥25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement obtained either at baseline (if no decrease) or best response, on stable or increasing doses of corticosteroids\*; significant increase in T2/FLAIR nonenhancing lesion on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy\* not caused by comorbid events; any new lesion; clear clinical deterioration not attributable to other causes apart from the tumor (eg, seizures, medication adverse effects) or changes in corticosteroid dose; failure to return for evaluation as a result of death or deteriorating condition; or clear progression of nonmeasurable disease.

John Flickinger

Professor of Radiation Oncology & Neurosurgery

Symptoms and General Pathology

Neoplasm Metastasis

Neuroendocrine Tumors

Neuroendocrine Tumor

Hematinics

Capecitabine

Liver Extracts

Antimetabolites

Capecitabine 750 mg/m2 twice daily orally for 14 days and temozolomide 200 mg/m2 orally on Days 10-14, with 14 days between cycles, to be continued until 1) disease progression or 2) intolerable toxicities.

Trans-arterial radioembolization (TARE) on Day 7 of cycle 2 and, if needed for the other lobe, Day 7 of either cycle 3 or 4.

Capecitabine 750 mg/m2 twice daily orally for 14 days

Capecitabine Oral Product

temozolomide 200 mg/m2 orally on Days 10-14, with 14 days between cycles

Trans-arterial radioembolization (TARE) on Day 7 of cycle 2 and, if needed for the other lobe, Day 7 of either cycle 3 or 4.

transarterial radioembolization

Michael Soulen, MD

Kathleen Thomas

Deepon Paul Singh

Renuka Iyer, MD

Abashai Woodard

Michael Soulen

This is a Phase 2 evaluation of hepatic-progression free survival among patients with Grade 2 liver-dominant NET metastases undergoing combination therapy with CapTem and Y90 radioembolization.The hypothesis is to confirm safety and to assess if disease control is improved relative to expectation from either therapy alone.

Patients with liver-dominant Grade 2 NET metastases from any primary will start CapTem and undergo simulation angiography for radioembolization planning during the first cycle. If they tolerate CapTem and are not excluded from radioembolization, then TARE will be performed on Day 7 of Cycle 2, with additional TARE of Day 7 of cycle 3 or 4 as needed to treat the entire tumor burden. Patients will remain on CapTem until progression or intolerance.

Primary outcome measure is hepatic progression-free survival.

CapTemY90 for Grade 2 NET Liver Metastases

UPCC 04219 Phase 2 Study of Capecitabine-Temozolomide(CapTem) With Yttrium-90 Radioembolization in the Treatment of Patients With Unresectable Metastatic Grade 2 Neuroendocrine Tumors

Intra-hepatic progression-free survival by RECIST 1.0 is defined as the time from initiation of study therapy until first documented intra-hepatic disease progression, death due to any cause or last scan date that documented intra-hepatic progression-free status.

Overall progression-free survival is defined as the time from initiation of study therapy until first documented intra- or extra-hepatic disease progression, death due to any cause or last scan date that documented progression-free status

Intra-hepatic tumor responses will be evaluated by RECIST.

Intra-hepatic tumor responses will be evaluated by EASL criteria.

extra-hepatic tumor responses will be evaluated by RECIST.

Systemic toxicities will be individually assessed by NCI CTCAE Version 4.

Hepatic toxicities will be individually assessed by NCI CTCAE Version 4.

The primary marker is CgA. Additional cancer site-specific (i.e., gastrinoma) markers may also be assayed.

Quality of Life will be measure by a validated NET-specific instrument, EORTC. Scale is 0-100, higher scores indicate worse symptoms/functioning

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
TN-TC11G (THC+CBD) Combination With Temozolomide and Radiotherapy in Patients With Newly-diagnosed Glioblastoma	NCT03529448	Glioblastoma	TN-TC11G Temozolomide Or... Radiotherapy	18 Years - 70 Years	Grupo Español de Investigación en Neurooncología
TN-TC11G (THC+CBD) Combination With Temozolomide and Radiotherapy in Patients With Newly-diagnosed Glioblastoma	NCT03529448	Glioblastoma	TN-TC11G Temozolomide Or... Radiotherapy	18 Years - 70 Years	Grupo Español de Investigación en Neurooncología
Short Course Chemo-Radiation Therapy for Patients With Newly Diagnosed Glioblastoma	NCT04019262	Glioblastoma	Radiation Thera... Temozolomide Or...	18 Years -	University of Pittsburgh
CapTemY90 for Grade 2 NET Liver Metastases	NCT04339036	Neuroendocrine ... Neuroendocrine ...	Capecitabine Or... Temozolomide Or... transarterial r...	18 Years -	Abramson Cancer Center at Penn Medicine
CapTemY90 for Grade 2 NET Liver Metastases	NCT04339036	Neuroendocrine ... Neuroendocrine ...	Capecitabine Or... Temozolomide Or... transarterial r...	18 Years -	Abramson Cancer Center at Penn Medicine

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