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A Phase I/II Study Of A Recombinant Chimeric Protein Composed Of Transforming Growth Factor (TGF)-a And A Mutated Pseudomonas Exotoxin Termed PE38 (TP-38) In Pediatric Patients With Recurrent Or Progressive Supratentorial High Grade Gliomas

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Ce qui est testé

Collecte de données

Qui peut participer

Néoplasmes par site
+2

+ Néoplasmes
+ Néoplasmes du système nerveux
De 3 à 21 ans
Voir tous les critères d'éligibilité
Comment se déroule l'étude

Étude thérapeutique

Phase 1 & 2
Interventionnel
Date de début : mai 2004
Voir le détail du protocole

Résumé

Sponsor principalPediatric Brain Tumor Consortium
Dernière mise à jour : 14 janvier 2026
Issu d'une base de données validée par les autorités. Revendiquer cette étude
Date de début de l'étude : 1 mai 2004Date à laquelle le premier participant a commencé l'étude.

OBJECTIVES: Primary * Phase I * Determine the maximum safe volume rate and maximum tolerated infusion concentration of TGFa-PE38 toxin (TP-38) infused through 2 or 3 catheters in pediatric patients with recurrent or progressive supratentorial high-grade glioma. * Describe the toxic effects of this drug in these patients. * Phase II * Estimate the efficacy of this drug, in terms of post-infusion survival, in these patients. Secondary * Phase I and II * Determine the prevalence of epidermal growth factor receptor (EGFR) expression and phosphorylation (activity) in patients treated with this drug. * Correlate EGFR expression with qualitative measures (e.g., histology, grade, and other tumor characteristics) and tumor response, survival, and progression-free survival in patients treated with this drug. * Phase II Only * Estimate the objective response rate in patients treated with this drug. * Estimate the progression-free survival of patients treated with this drug. OUTLINE: This is a dose-escalation, multicenter study. Patients in the phase I portion of the study are stratified according to the number of successfully placed catheters (3 catheters vs 2 catheters). Patients in the phase II portion of the study are stratified according to time of recurrence of high-grade glioma (first vs second or greater) and by surgery extent (surgical resection vs stereotactic biopsy) for those with first recurrence only. * Phase I: Patients undergo stereotactic biopsy or resection of the tumor followed by intratumoral (or tumor bed) catheter placement for treatment infusion. Within 12-48 hours after intratumoral (or tumor bed) catheter placement, patients receive TGFa-PE38 toxin (TP-38) intratumorally through 2 or 3 catheters over 33 to 124 hours. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients (in each stratum) receive escalating volumes until the maximum safe volume (MSV) is determined. Cohorts of 3-6 patients (in each stratum) receive escalating concentrations at the MSV until the maximum tolerated infusion concentration (MTIC) is determined. The MSV and MTIC are defined as the volume and concentration preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. * Phase II: Patients receive treatment as in phase I at the MSV and MTIC. Phase I patients are followed post catheter placement, daily during TP-38 infusion, at 30 days, and then every 2 months for 1 year. Phase II patients will be followed for an additional year. PROJECTED ACCRUAL: A total of 6-105 patients (6-60 for phase I and 45 for phase II) will be accrued for this study.

Titre officielA Phase I/II Study Of A Recombinant Chimeric Protein Composed Of Transforming Growth Factor (TGF)-a And A Mutated Pseudomonas Exotoxin Termed PE38 (TP-38) In Pediatric Patients With Recurrent Or Progressive Supratentorial High Grade Gliomas 
NCT00074334
Sponsor principalPediatric Brain Tumor Consortium
Dernière mise à jour : 14 janvier 2026
Issu d'une base de données validée par les autorités. Revendiquer cette étude

Protocole

Cette section fournit des détails sur le plan de l'étude, y compris la manière dont l'étude est conçue et ce qu'elle évalue.
Détails du design
3 participants à inclureNombre total de participants que l'essai clinique vise à recruter.
Traitement
Cette étude teste un ou plusieurs traitements pour évaluer leur efficacité contre une maladie ou un problème de santé spécifique. L'objectif est de voir si un nouveau médicament ou une thérapie fonctionne mieux, ou provoque moins d'effets secondaires que les options existantes.

Éligibilité

Les chercheurs recherchent des patients correspondant à une certaine description appelée critères d'éligibilité : état de santé général ou traitements antérieurs du patient.
Conditions
Critères
Tout sexeLe sexe biologique des participants éligibles à s'inscrire.
De 3 à 21 ansTranche d'âge des participants éligibles à participer.
Volontaires sains non autorisésIndique si les individus en bonne santé et ne présentant pas la condition étudiée peuvent participer.
Conditions
Pathologie
Néoplasmes par site
Néoplasmes
Néoplasmes du système nerveux
Maladies du système nerveux
Néoplasmes du système nerveux central
Critères

DISEASE CHARACTERISTICS: * Histologically confirmed supratentorial malignant glioma * Recurrent or progressive disease * Amenable to gross total resection, clinically indicated partial resection, or biopsy * Tumor must have a single solid portion at least 1 cm and no greater than 5 cm in maximum diameter * No tumor crossing midline * Tumors invading the corpus callosum that do not extend beyond to midline or into the contralateral hemisphere allowed * No more than 1 focus of tumor * No tumors involving the brainstem or cerebellum * No tumor dissemination (i.e., subependymal or leptomeningeal) * Must be on steroids ≥ 3 days prior to surgery * Must have received prior external beam radiotherapy (tumor dose at least 45 Gy) and completed therapy at least 8 weeks before study entry * No impending herniation, including midline shift greater than 0.5 cm * No requirement for immediate palliative treatment PATIENT CHARACTERISTICS: Age * 3 to 21 Performance status * Karnofsky 60-100% (patients over 16 years of age) OR * Lansky 60-100% (patients age 16 and under) Life expectancy * Not specified Hematopoietic * Absolute neutrophil count at least 1,500/mm\^3 * Platelet count at least 100,000/mm\^3\* * Hemoglobin at least 9 g/dL\* NOTE: \*Transfusion independent Hepatic * ALT and AST less than 2.5 times upper limit of normal (ULN) * PT and PTT no greater than ULN Renal * Creatinine less than 1.5 times normal OR * Glomerular filtration rate greater than 70 mL/min Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for at least 30 days after study participation * No uncontrolled seizures * No active infection requiring treatment * No unexplained febrile illness * No known or suspected allergies to local anesthetics * No systemic disease or other condition that may be associated with unacceptable anesthetic/operative risk and/or that would preclude study completion * No other malignancy within the past 5 years except curatively treated carcinoma in situ or basal cell skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy * At least 8 weeks since prior hematopoietic stem cell transplantation Chemotherapy * At least 6 months since prior polifeprosan 20 with carmustine implant (Gliadel® wafer) * At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosoureas and 2 weeks for vincristine) * At least 2 weeks since prior non-cytotoxic chemotherapy * No other prior intracerebral chemotherapy * No concurrent chemotherapy Endocrine therapy * Concurrent steroids allowed Radiotherapy * See Disease Characteristics * No prior focal radiotherapy (e.g., gamma knife radiosurgery, stereotactic radiosurgery, or brachytherapy) * No concurrent radiotherapy Surgery * Not specified Other * Recovered from prior therapy * At least 4 weeks since prior anticancer investigational agents * No prior localized antitumor therapy for malignant glioma * No other concurrent investigational agent * No other concurrent anticancer (including alternative anticancer medicines/treatment) agent or therapy

Plan de l'étude

Découvrez tous les traitements administrés dans cette étude, leur description détaillée et ce qu'ils impliquent.
Objectifs de l'étude
Objectifs de l'étude
Objectifs principaux

Objectifs secondaires

Centres d'étude

Ce sont les hôpitaux, cliniques ou centres de recherche où l'essai est conduit. Vous pouvez trouver le site le plus proche de vous ainsi que son statut.
Cette étude comporte 8 sites
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Children's National Medical CenterWashington, United StatesVoir le site
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Children's Memorial Hospital - ChicagoChicago, United States
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Dana-Farber/Harvard Cancer Center at Dana Farber Cancer InstituteBoston, United States
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Duke Comprehensive Cancer CenterDurham, United States
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