Phase i trial of UNBS5162, a novel naphthalimide in patients with advanced solid tumors or lymphoma

Daruka Mahadevan, Donald W Northfelt, Pavani Chalasani, Diane Rensvold, Sandra Kurtin, Daniel D. Von Hoff, Mitesh J Borad, Raoul Tibes

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Objectives: UNBS5162 is a novel naphthalimide that binds to DNA by intercalation and suppresses CXCL chemokine elaboration. A Phase I study of UNBS5162 was conducted to establish pharmacokinetics (PK), maximum tolerated dose (MTD), dose-limiting toxicity, safety and anti-tumor activity in patients with advanced solid tumors or lymphoma. Methods: UNBS5162 was administered in a 3 + 3 dose escalation scheme by intravenous infusion over 1 h weekly for 3 weeks of a 4-week cycle. Safety, serial serum PK and tolerability were captured throughout the study. Response Evaluation Criteria in Solid Tumors was utilized every 2 cycles to assess for anti-tumor response. Results: Twenty-four patients with metastatic carcinoma and 1 patient with lymphoma were treated at eight dose levels (18-234 mg/m2). All patients were evaluable for tolerability and toxicity. Grade 3 toxicities include nausea (n = 1), fatigue (n = 1) and anorexia (n = 1). Prolongation of QTc [Hodges] was observed in 6 cases (Gr 1 = 2; Gr 2 = 2; Gr 3 = 2). C max and area under the curve increased linearly with dose with a t 1/2 of 30-60 min. 16 patients completed 2 cycles of therapy, all with pharmacodynamics at 8 weeks. Conclusions: The MTD or dose-limiting toxicity for UNBS5162 was not reached due to the magnitude of QTc prolongation at the highest dose of 234 mg/m2/week that led to study termination.

Original languageEnglish (US)
Pages (from-to)934-941
Number of pages8
JournalInternational Journal of Clinical Oncology
Volume18
Issue number5
DOIs
StatePublished - Oct 2013

Fingerprint

Naphthalimides
Lymphoma
Maximum Tolerated Dose
Neoplasms
Pharmacokinetics
Safety
Anorexia
Chemokines
Intravenous Infusions
Nausea
Area Under Curve
Fatigue
UNBS 5162
Carcinoma
DNA
Serum

Keywords

  • Chemokines
  • Dose-limiting toxicity
  • Maximum tolerated dose
  • Naphthalimide
  • QTc

ASJC Scopus subject areas

  • Oncology
  • Surgery
  • Hematology

Cite this

Phase i trial of UNBS5162, a novel naphthalimide in patients with advanced solid tumors or lymphoma. / Mahadevan, Daruka; Northfelt, Donald W; Chalasani, Pavani; Rensvold, Diane; Kurtin, Sandra; Von Hoff, Daniel D.; Borad, Mitesh J; Tibes, Raoul.

In: International Journal of Clinical Oncology, Vol. 18, No. 5, 10.2013, p. 934-941.

Research output: Contribution to journalArticle

Mahadevan, Daruka ; Northfelt, Donald W ; Chalasani, Pavani ; Rensvold, Diane ; Kurtin, Sandra ; Von Hoff, Daniel D. ; Borad, Mitesh J ; Tibes, Raoul. / Phase i trial of UNBS5162, a novel naphthalimide in patients with advanced solid tumors or lymphoma. In: International Journal of Clinical Oncology. 2013 ; Vol. 18, No. 5. pp. 934-941.
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