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Phase 1 study of napabucasin, a cancer stemness inhibitor, in patients with advanced solid tumors.
- Source :
-
Cancer chemotherapy and pharmacology [Cancer Chemother Pharmacol] 2020 May; Vol. 85 (5), pp. 855-862. Date of Electronic Publication: 2020 Mar 31. - Publication Year :
- 2020
-
Abstract
- Purpose: Napabucasin is a cancer stemness inhibitor that targets a number of oncogenic pathways, including signal transducer and activator of transcription 3 (STAT3). Phase 1/2 studies suggest tolerability and anti-tumor activity in various types of cancer; a Phase 3 study of napabucasin plus standard therapy in colorectal cancer is ongoing. This is a Phase 1 dose-escalation study in patients with advanced solid tumors, and the first study of napabucasin in Japanese patients.<br />Methods: Patients received napabucasin 480, 960, or 1440 mg daily in 28-day cycles until disease progression or intolerable toxicity. Primary objectives were to determine dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and the pharmacokinetic (PK) profile of napabucasin. Blood samples were taken for PK analysis on Days 1, 2, 8, and 15 of Cycle 1, and Days 29 and 30 of Cycle 2. Secondary objectives were to assess napabucasin antitumor activity, and the relationship between biomarkers and antitumor activity. JapicCTI-No: JapicCTI-132152.<br />Results: Enrolled were 14 patients (480 mg [n = 3], 960 mg [n = 4], 1440 mg [n = 7]). One patient experienced a DLT (Grade 3, anorexia). MTD was 1440 mg/day. Most common drug-related adverse events were diarrhea (n = 9), nausea (n = 4), vomiting (n = 3), and anorexia (n = 3). Napabucasin showed a similar PK profile to previous studies and no abnormal accumulation was observed. Following treatment, two patients had stable disease; the remaining 12 had progressive disease.<br />Conclusion: Napabucasin was well-tolerated at doses up to 1440 mg/day in Japanese patients with advanced solid tumors; the PK profile was comparable to that reported previously.
- Subjects :
- Adrenal Gland Neoplasms pathology
Antineoplastic Agents administration & dosage
Antineoplastic Agents adverse effects
Antineoplastic Agents pharmacokinetics
Biological Availability
Colorectal Neoplasms pathology
Dose-Response Relationship, Drug
Drug Administration Schedule
Drug Monitoring methods
Drug-Related Side Effects and Adverse Reactions diagnosis
Female
Humans
Male
Maximum Tolerated Dose
Middle Aged
Progression-Free Survival
Treatment Outcome
Adrenal Gland Neoplasms drug therapy
Benzofurans administration & dosage
Benzofurans adverse effects
Benzofurans pharmacokinetics
Colorectal Neoplasms drug therapy
Naphthoquinones administration & dosage
Naphthoquinones adverse effects
Naphthoquinones pharmacokinetics
STAT3 Transcription Factor antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1432-0843
- Volume :
- 85
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cancer chemotherapy and pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 32236642
- Full Text :
- https://doi.org/10.1007/s00280-020-04059-3