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Parallel phase Ib studies of two schedules of buparlisib (BKM120) plus carboplatin and paclitaxel (q21 days or q28 days) for patients with advanced solid tumors

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Abstract

Purpose

Phosphatidylinositol-3-kinase I (PI3K) inhibition sensitizes a wide range of cancer cell lines to platinum/taxane-based chemotherapy. This phase I study combines buparlisib, a pan-class 1A PI3K inhibitor, with two schedules of carboplatin and paclitaxel for patients with advanced solid tumors (ClinicalTrials.gov, NCT01297452).

Methods

There were two regimens: Group 1 received carboplatin AUC 5 and paclitaxel 175 mg/m2, on day 1 of a 21-day cycle with pegfilgrastim support; Group 2 received carboplatin AUC 5 (day 1) and paclitaxel 80 mg/m2 (days 1, 8, and 15) on a 28-day cycle without growth factor support. In both groups, three dose levels of buparlisib were explored: 50, 80, and 100 mg/day. Primary endpoint was to identify recommended phase II doses of buparlisib in both groups.

Results

Thirty subjects enrolled, 16 in Group 1 and 14 in Group 2. The DLTs were elevated alkaline phosphatase (n = 1) and uncomplicated neutropenia (n = 2). The median numbers of cycles were 5 (Group 1) and 6 (Group 2). The MTDs for buparlisib were 100 mg/day in Group 1 and 80 mg/day in Group 2. Among 25 patients with measurable disease, the confirmed objective response rate was 20 % (one complete response, four partial responses). Among three patients with known loss of PTEN expression, all derived clinical benefit from treatment.

Conclusion

The addition of buparlisib to carboplatin + paclitaxel was well tolerated, and preliminary activity was notable against tumors with loss of PTEN expression.

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Acknowledgments

They also thank Saiprasad Boddu, of Sai Life Sciences, for pharmacokinetic analyses. ClinicalTrials.gov identifier: NCT01297452. The study site received funding from Novartis Pharmaceuticals.

Conflict of interest

M.F., A.H., R.C., M.L, and M.V. have served on advisory boards and/or consulted for Novartis. No potential conflict of interest was disclosed by the other authors.

Author information

Authors and Affiliations

  1. Developmental Therapeutics Clinic and Head and Neck Service, Department of Medicine, Breast and Imaging Center, Memorial Sloan Kettering Cancer Center (MSKCC) and Weill Cornell Medical College, 300 East 66th Street, Room 1453, New York, NY, USA

    Matthew G. Fury

  2. Developmental Therapeutics Clinic, Department of Medicine, Memorial Sloan Kettering Cancer Center (MSKCC), 1275 York Avenue, New York, NY, USA

    David M. Hyman, Alexandra E. Snyder, Richard D. Carvajal, John F. Gerecitano, Martin H. Voss, Alan L. Ho, Jason Konner, Jennifer L. Winkelmann, Megan A. Stasi, Kelsey R. Monson & David R. Spriggs

  3. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY, USA

    Alexia Iasonos

  4. Department of Psychiatry, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY, USA

    Philip Bialer

  5. Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY, USA

    Mario E. Lacouture

  6. Department of Radiology, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY, USA

    Jerrold B. Teitcher

  7. Department of Pathology, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY, USA

    Nora Katabi

Authors
  1. David M. Hyman
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  2. Alexandra E. Snyder
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  3. Richard D. Carvajal
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  5. Martin H. Voss
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  6. Alan L. Ho
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  8. Jennifer L. Winkelmann
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  9. Megan A. Stasi
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  10. Kelsey R. Monson
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  11. Alexia Iasonos
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  12. David R. Spriggs
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  13. Philip Bialer
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  14. Mario E. Lacouture
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  15. Jerrold B. Teitcher
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  16. Nora Katabi
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  17. Matthew G. Fury
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Corresponding author

Correspondence to Matthew G. Fury.

Additional information

Clinicaltrials.gov ID NCT01297452.

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Hyman, D.M., Snyder, A.E., Carvajal, R.D. et al. Parallel phase Ib studies of two schedules of buparlisib (BKM120) plus carboplatin and paclitaxel (q21 days or q28 days) for patients with advanced solid tumors. Cancer Chemother Pharmacol 75, 747–755 (2015). https://doi.org/10.1007/s00280-015-2693-z

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  • DOI: https://doi.org/10.1007/s00280-015-2693-z

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