A phase I safety and efficacy clinical trial of plocabulin and gemcitabine in patients with advanced solid tumors.
Invest New Drugs
; 2024 Aug 03.
Article
em En
| MEDLINE
| ID: mdl-39096398
ABSTRACT
Plocabulin (Plo) induces depolymerization of tubulin fibers with disorganization and fragmentation of the microtubule network leading to mitosis. Plo combined with gemcitabine (Gem) showed synergistic anti-tumor activity in preclinical studies. This phase I trial evaluated the safety, pharmacokinetics (PK) and efficacy of Plo 10-min infusion plus Gem on Day 1 and 8 every 3-week in patients with advanced solid tumors. Fifty-seven patients were enrolled into 8 dose levels (DLs); 74% females; 74% ECOG performance status 1; median age 62 years; median number of prior lines of therapy3. Dose-limiting toxicities (DLT) in Cycle 1 were grade (G) 3 intestinal obstruction at the maximum tolerated dose (MTD), G3 peripheral sensory neuropathy (PSN), G3 abdominal pain, and G4 thrombocytopenia (1 patient each). The highest DL (DL8 Plo 10.5 mg/m2/Gem 1000 mg/m2) was the MTD. Accrual into DL7 (Plo 10.0 mg/m2/Gem 1000 mg/m2) was stopped before it was formally defined as the recommended dose (RD). Most common treatment-related adverse events (AEs) were fatigue (56%), nausea (55%), diarrhea (31%); G3/4 hematologic toxicities comprised anemia (35%), neutropenia (27%) and thrombocytopenia (17%). No treatment-related deaths occurred. PK parameters for Gem or dFdU at all DLs were in line with reference values from the literature. Six of 46 evaluable pts were responders (overall response rate13%). Of note, 2 partial responses (PR) and 2 stable disease (SD) ≥ 4 months occurred among 13 pts with ovarian cancer. The combination of Plo and Gem is well tolerated. The MTD was Plo 10.5 mg/m2/Gem 1000 mg/m2. No PK drug-drug interaction was found. The most encouraging outcome occurred in ovarian cancer patients.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Invest New Drugs
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
Estados Unidos