Phase I/II study of CTCE-9908, a novel anticancer agent that inhibits CXCR4, in patients with advanced solid cancers
Notice bibliographique
Résumé
A153 Introduction: CTCE-9908 is a 17 amino acid peptide CXCR4 antagonist that has been shown to block the interaction of the CXCR4 receptor with CXCL12 (SDF-1), critical in the infiltration of organ tissues by metastatic cells. CXCR4 receptors are expressed on many malignant cell types. SDF-1, the CXCR4 ligand is produced in large amounts by organs representing the first sites of metastasis for many malignant cell types. Recently, CXCR4 has also been shown to play a role in angiogenesis. CTCE-9908 is expected to be effective against a wide range of cancer types that express CXCR4 by inhibiting the metastatic process. This phase I/II study was designed to determine the maximal tolerated dose (MTD), toxicity profile, pharmacokinetics and antitumor activity of CTCE-9908 in patients (pts) with refractory late-stage solid tumors. Patients and Methods: The agent was administered over 30 minutes, intravenously daily during weekdays for 20 doses in escalating doses to eligible pts using an accelerated titration design. Five dose levels (DLs) from 0.25mg/kg to 5.0mg/kg were planned. Twenty-two pts have been entered in 5 cohorts: DL 1 (0.25) - 2 pts; DL 2 (0.5) - 1 pt; DL 3 (1.0) - 4 pts; DL 4 (2.5) - 2 pts; DL 5 (5) - 13 pts. Twenty-one pts received study drug since one pt at DL1 progressed prior to starting treatment. DL 5 was expanded to obtain more information on toxicity and efficacy specific to pts with ovarian, breast, prostate and ‘other’ CXCR4-expressing cancers. Pts with stable disease (SD) or better after cycle 1 were eligible to receive further cycles. For 21 evaluable pts, median age was 56 years (range, 30-84), 62% were female. Primary tumor types: breast (6 pts), ovary (4 pts), lung (3 pts), melanoma (2 pts), others (6 pts). Results: Adverse event (AE) data are available for the first 21 pts. No pt had DLT. Most common drug-related toxicity consisted of grade 2 phlebitis (3pts), grade 2 gingivitis (2 pts) and grade 3 GGT elevation (1 pt). Of 20 pts assessable for response: PD (10), SD (5), N/A (5). Of the pts with SD after first cycle, 3 had ovarian cancer, 2 had breast cancer and 1 had small bowel cancer. Seven pts entered the continuation phase after cycle 1. One pt with small bowel cancer has now completed 4 cycles of therapy. One pt with ovarian cancer had a decrease in CA-125 from 657 to 303 after 1 cycle with a decrease in baseline target lesions but was found to have a brain metastasis not evaluated on screening, presumably from a concurrent breast cancer. Conclusions: CTCE-9908, an anticancer agent with a novel mechanism of action, is well tolerated and has shown preliminary signs of efficacy, especially in ovarian cancer. A phase II study is planned in that population. The expansion phase of the current trial continues and should complete accrual shortly.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
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 | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| 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 | 0,000 |
| 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 ».