Abstract OT1-06-01: ANG1005 in leptomeningeal disease (ANGLeD) trial: A randomized, open-label, phase 3 study of ANG1005 compared with Physician's Best Choice in HER2-negative breast cancer patients with newly diagnosed leptomeningeal carcinomatosis and previously treated brain metastases
Notice bibliographique
Résumé
Abstract Background: Annually, more than 4,000 patients are diagnosed with leptomeningeal carcinomatosis (LC) from breast cancer in the U.S. Since most therapies cannot cross the Blood-CSF-Barrier (BCB) and the Blood-Brain-Barrier (BBB), treatment options for LC are limited to local radiation and few chemotherapy agents, none of which have provided durable clinical benefit, leading to short overall survival (OS) of 3-4 months. ANG1005 is a novel peptide-drug conjugate, consisting of 3 paclitaxel molecules covalently linked to a peptide that targets the LRP-1 receptor to cross both BCB and BBB, and enter the tumor cells, where the paclitaxel is cleaved off to exert its anti-tumor activity. ANG1005 has previously shown in a phase 2 study to prolong OS in LC patients from breast cancer with brain metastases (BM) to 8 months. Trial Design: This is an open-label, multi-center phase 3 randomized study to evaluate the efficacy of ANG1005 in HER2-negative breast cancer patients with newly diagnosed LC and documented history of previously treated BM when compared to Physician Best Choice (PBC). Hundred and fifty (150) patients will be randomized 1:1 to receive either ANG1005 experimental treatment or an Investigator assigned PBC control treatment. ANG1005 will be administered by intravenous (IV) infusion at a starting dose of 600 mg/m2 every 3 weeks. Allowed PBC therapies include capecitabine, eribulin, or high-dose IV methotrexate. CNS disease (LC and BM) will be evaluated at screening and every 6 weeks by MRI, CSF cytology and neurological assessments according to LANO and RANO-BM criteria. Extracranial disease will be evaluated by CT scans according to RECIST at screening and every 6-12 weeks. All patients will be followed for survival every 6-8 weeks from the date of the last dose until death, lost to follow-up or consent withdrawal. Eligibility Criteria: Eligible patients are adults (≥ 18 years old) with HER2-negative breast cancer, newly diagnosed LC and documented history of previously treated BM. Patients must be neurologically stable and have adequate blood counts, organ and bone marrow function with an ECOG status grade ≤2. Patients previously treated with ANG1005 or with known allergy to paclitaxel or its components are excluded. Specific aims: The primary endpoint is OS. Secondary endpoints include CNS (LC and BM) progression-free survival and clinical benefit rate, 6- and 12-month OS rates, LC response rate and duration of response, OS for triple negative patients and safety. Statistical Methods: This study is sized for testing the hypothesis of improved OS for ANG1005 versus PBC in all patients (HR=0.58, two-sided test, overall type 1 error of 5%). Interim analysis for OS (using O'Brien Fleming boundaries for efficacy and a fixed HR=1 for futility) will be performed when a total of 55 death events are reached across both arms. Study Accrual: Target accrual is 150 patients. The study is currently planned to start in the fall of 2018. Citation Format: Kumthekar P, Lawrence B, Iordanova V, Ibrahim N, Mazanet R. ANG1005 in leptomeningeal disease (ANGLeD) trial: A randomized, open-label, phase 3 study of ANG1005 compared with Physician's Best Choice in HER2-negative breast cancer patients with newly diagnosed leptomeningeal carcinomatosis and previously treated brain metastases [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT1-06-01.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,000 |
| Bibliométrie | 0,001 | 0,002 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».