- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT07605364
Testing the Addition of an Anti-Cancer Drug, Mycophenolate Mofetil, to the Usual Treatment (Radiation Therapy and Temozolomide) for Advanced Brain Cancer
Mycophenolate Mofetil to Overcome Glioblastoma Resistance to Radiotherapy and Temozolomide
Aperçu de l'étude
Statut
Les conditions
Description détaillée
The primary and secondary objectives of the study:
PRIMARY OBJECTIVE:
I. To compare the overall survival (OS) (phase III) and progression-free survival (PFS) (phase II) between the experimental arm (mycophenolate mofetil [MMF] + standard of care [SOC]) and the control arm (SOC).
SECONDARY OBJECTIVES:
I. To compare the proportion of patients with an objective tumor response (ORR), measured with Response Assessment in Neuro-Oncology (RANO) 2.0 criteria, between the two treatment arms.
II. To determine the adverse event profiles for each arm (using the current latest version of Common Terminology Criteria for Adverse Events [CTCAE]).
III. To determine if there is an association between OS and PFS between treatment arms.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients under 70 years undergo intensity modulated radiation therapy (IMRT), Monday-Friday for 30 treatments and patients greater than or equal to 70 years undergo hypofractionated radiation therapy, Monday-Friday for 15 treatments in the absence of disease progression or unacceptable toxicity. Starting 24 hours prior to radiation, patients also receive temozolomide orally (PO) once daily (QD) until the day of the last radiation treatment, in the absence of disease progression or unacceptable toxicity. Patients then undergo a 4-week rest period. Patients then receive temozolomide PO QD on days 1-5 of each cycle. Cycles repeat every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo magnetic resonance imaging (MRI) and blood sample collection throughout the study.
ARM II: Patients under 70 years undergo IMRT, Monday-Friday for 30 treatments and patients greater than or equal to 70 years undergo hypofractionated radiation therapy, Monday-Friday for 15 treatments in the absence of disease progression or unacceptable toxicity. Starting 24 hours prior to radiation, patients also receive temozolomide PO QD until the day of the last radiation treatment, and, starting on the first day of radiation, patients also receive mycophenolate mofetil PO twice daily (BID) in the absence of disease progression or unacceptable toxicity. Patients then undergo a 4-week rest period. Patients then receive temozolomide PO QD on days 1-5 and mycophenolate mofetil PO BID on days 1-28 of each cycle. Cycles repeat every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo MRI and blood sample collection throughout the study.
After completion of study treatment, patients are followed up every 10 weeks until 2 years then every 6 months until 5 years.
Type d'étude
Inscription (Estimé)
Phase
- Phase 2
- Phase 3
Contacts et emplacements
Coordonnées de l'étude
- Nom: Amanda Clark
- Numéro de téléphone: (773) 702-9171
- E-mail: neurooncologyprotocols@alliancenctn.org
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
- Adulte
- Adulte plus âgé
Accepte les volontaires sains
La description
Inclusion Criteria:
- Newly diagnosed primary glioblastoma by World Health Organization (WHO) 2021 criteria
- No spinal cord glioblastoma
- No leptomeningeal disease
- No extracranial metastatic disease
- Patient is a candidate for first-line standard of care chemoradiation per treating physician(s)
- No prior treatment for glioblastoma other than resection (i.e. prior chemotherapy, radiation therapy, or other therapies such as laser ablation are not allowed)
- Prior biopsy and/or resection of glioblastoma must be completed at least 14 days prior to registration with adequate wound healing
- Age ≥ 18 years
- Karnofsky performance status (KPS) ≥ 60
- Absolute neutrophil count (ANC) ≥ 1,500/mm^3
- Platelet count ≥ 100,000 cells/mm^3
- Hemoglobin (Hg) ≥ 9.0 g/dL
Calculated (Calc.) creatinine clearance (CrCl) ≥ 25 mL/min
* Calculated using the Cockcroft-Gault equation
- Bilirubin ≤ 1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3.0 x ULN
- Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects.
Therefore, for women of childbearing potential only, a negative pregnancy test done ≤ 14 days prior to registration is required.
Women and men of reproductive potential must agree to use a highly effective method of birth control throughout their participation in this study and for at least 6 weeks (women) or 90 days (men) after last dose of treatment. Reproductive status and discussions about birth control measures should be documented in the patient's record. Appropriate methods of birth control include, but are not limited to: abstinence, oral contraceptives, implantable hormonal contraceptives or double barrier method (diaphragm plus condom)
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
- HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- No known history of allergic reaction or hypersensitivity to mycophenolate mofetil (MMF), mycophenolic acid (MPA), or any component of the drug product
- No known history of hypersensitivity reactions to temozolomide (TMZ) or other ingredients in TMZ
- No known medical condition causing an inability to swallow oral formulations of agents
- No active systemic or central nervous system (CNS) infection
- No grade 4 lymphopenia (if absolute lymphocyte count [ALC] < 0.5, then patient must be on prophylaxis for Pneumocystis jirovecii)
- No known history of organ transplantation
- No known hypoxanthine-guanine phosphoribosyl-transferase deficiency
- No known serious intercurrent illness that limits participation in the trial
- No known immunosuppressive condition from autoimmune disease, immune deficiency syndrome, or chronic immunosuppressive therapy
- Patient must be able to undergo MRI brain with and without contrast
- No known phenylketonuria
- No known medical contraindication for mycophenolate mofetil (MMF) per treating physician(s)
- Patients on steroids must be on stable or decreasing dose within 7 days of registration (no more than 8 mg dexamethasone/day or equivalent)
Exclusion Criteria:
-
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: Arm I (radiation, temozolomide)
Patients under 70 years undergo IMRT, Monday-Friday for 30 treatments and patients greater than or equal to 70 years undergo hypofractionated radiation therapy, Monday-Friday for 15 treatments in the absence of disease progression or unacceptable toxicity.
Starting 24 hours prior to radiation, patients also receive temozolomide PO QD until the day of the last radiation treatment, in the absence of disease progression or unacceptable toxicity.
Patients then undergo a 4-week rest period.
Patients then receive temozolomide PO QD on days 1-5 of each cycle.
Cycles repeat every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
Patients undergo MRI and blood sample collection throughout the study.
|
Passer une IRM
Subir IMRT
Autres noms:
Subir une radiothérapie hypofractionnée
Donné po.
undergo Biospecimen Collection
|
|
Expérimental: Arm II (radiation, temozolomide, mycophenolate mofetil)
Patients under 70 years undergo IMRT, Monday-Friday for 30 treatments and patients greater than or equal to 70 years undergo hypofractionated radiation therapy, Monday-Friday for 15 treatments in the absence of disease progression or unacceptable toxicity.
Starting 24 hours prior to radiation, patients also receive temozolomide PO QD until the day of the last radiation treatment, and, starting on the first day of radiation, patients also receive mycophenolate mofetil PO twice daily (BID) in the absence of disease progression or unacceptable toxicity.
Patients then undergo a 4-week rest period.
Patients then receive temozolomide PO QD on days 1-5 and mycophenolate mofetil PO BID on days 1-28 of each cycle.
Cycles repeat every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
Patients undergo MRI and blood sample collection throughout the study.
|
Passer une IRM
Subir IMRT
Autres noms:
Bon de commande donné
Donné po.
undergo Biospecimen Collection
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Progression free survival (PFS) (phase II)
Délai: From randomization to the disease progression according to Response Assessment in Neuro-Oncology (RANO) 2.0 criteria or death due to any cause, up to 5 years
|
PFS will be calculated from randomization until disease progression according to RANO 2.0 criteria or death due to any cause, censoring patients at their last disease evaluation.
The Kaplan-Meier method will be used to estimate PFS for each arm and a stratified log-rank test will be used to compare distributions
|
From randomization to the disease progression according to Response Assessment in Neuro-Oncology (RANO) 2.0 criteria or death due to any cause, up to 5 years
|
|
Overall survival (OS) (phase III)
Délai: From randomization until death due to any cause, up to 5 years
|
OS will be calculated from randomization until death due to any cause, censoring patients at their last disease evaluation.
The Kaplan-Meier method will be used to estimate OS for each arm and a stratified log-rank test will be used to compare distributions.
|
From randomization until death due to any cause, up to 5 years
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Tumor response
Délai: Up to 5 years
|
Defined as a complete response or partial response as determined using RANO 2.0.
|
Up to 5 years
|
|
Incidence of adverse events
Délai: Up to 5 years
|
Determined by the most recent version of Common terminology Criteria for Adverse Events.
|
Up to 5 years
|
|
Overall survival (OS)
Délai: From randomization until death due to any cause, up to 5 years
|
Kaplan Meier methods will be used to estimate key aspects of the OS distributions for each of the treatment arms, and log rank tests will be used to compare these distributions between arms.
|
From randomization until death due to any cause, up to 5 years
|
|
Progression free survival (PFS)
Délai: From randomization to the disease progression according to RANO 2.0 criteria or death due to any cause, up to 5 years
|
Kaplan-Meier methods will be used to estimate key aspects of the PFS distributions for each of the treatment arms, and log-rank tests will be used to compare these distributions between arms.
|
From randomization to the disease progression according to RANO 2.0 criteria or death due to any cause, up to 5 years
|
Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Chaise d'étude: Priya Kumthekar, MD, Alliance for Clinical Trials in Oncology
- Chaise d'étude: Yoshie Umemura, MD, MS, Alliance for Clinical Trials in Oncology
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Estimé)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Produits chimiques organiques
- Composés hétérocycliques, 1 anneau
- Composés hétérocycliques
- Techniques d'investigation
- Thérapeutique
- Acides gras
- Lipides
- Azoles
- Acides, acyclique
- Acides carboxyliques
- Dacarbazine
- Triazènes
- Imidazoles
- Techniques de chimie, analytique
- Analyse du spectre
- Radiothérapie
- Radiothérapie, conforme
- Radiothérapie, assistée par ordinateur
- Caproates
- Témozolomide
- Acide mycophénolique
- Spectroscopie de résonance magnétique
- Radiothérapie, intensité modulée
Autres numéros d'identification d'étude
- A072402
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Étudie un produit d'appareil réglementé par la FDA américaine
produit fabriqué et exporté des États-Unis.
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