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

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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.

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Acknowledgments

We wish to thank the patients and their families, clinical research support services (CRSS) at the Arizona Cancer Center, Mayo Clinic, AZ, USA and Virginia G. Piper Cancer Center at Scottsdale Healthcare, Nikki Barkett RN and Drias Pharmaceuticals for support.

Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Arizona Cancer Center, Tucson, AZ, USA

    Daruka Mahadevan, Pavani Chalasani, Diane Rensvold & Sandra Kurtin

  2. Mayo Clinic, Scottsdale, AZ, USA

    Donald W. Northfelt, Mitesh J. Borad & Raoul Tibes

  3. Virginia G. Piper Cancer Center at Scottsdale Healthcare, Scottsdale, AZ, USA

    Daniel D. Von Hoff

Authors
  1. Daruka Mahadevan
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  2. Donald W. Northfelt
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  3. Pavani Chalasani
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  4. Diane Rensvold
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  5. Sandra Kurtin
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  6. Daniel D. Von Hoff
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  7. Mitesh J. Borad
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  8. Raoul Tibes
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Corresponding author

Correspondence to Daruka Mahadevan.

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Mahadevan, D., Northfelt, D.W., Chalasani, P. et al. Phase I trial of UNBS5162, a novel naphthalimide in patients with advanced solid tumors or lymphoma. Int J Clin Oncol 18, 934–941 (2013). https://doi.org/10.1007/s10147-012-0475-8

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  • DOI: https://doi.org/10.1007/s10147-012-0475-8

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