ProCAID: A randomized double-blind phase II clinical trial of capivasertib (C) in combination with docetaxel and prednisolone chemotherapy (DP) in metastatic castration-resistant prostate cancer (mCRPC)
Crabb, S. J. Griffiths, G. O. Marwood, E. Dunkley, D. Downs, N. Martin, K. Light, M. Northey, J. Whitehead, A. Shaw, E. C.
Crabb, S. J.
Griffiths, G. O.
Marwood, E.
Dunkley, D.
Downs, N.
Martin, K.
Light, M.
Northey, J.
Whitehead, A.
Shaw, E. C.
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Abstract
Background: DP extends survival in mCRPC, but clinical benefit is modest. PI3K/AKT/PTEN pathway activation is common in mCRPC contributing to disease progression and DP resistance. C is a pan-AKT inhibitor. Pre-clinical data indicate activity in prostate cancer and synergism with DP. This phase II trial combined C with DP in mCRPC. Methods: Key eligibility criteria: histologically or cytologically proven measurable or evaluable mCRPC, suitable for treatment with DP for PSA and/or radiographic disease progression, ECOG performance status 0-1, no prior chemotherapy for mCRPC, not requiring insulin or > 2 oral hypoglycaemic drugs for diabetes mellitus. Treatment: up to 10 cycles of DP (D: 75 mg/m2 IV, day 1; P: 5 mg bd oral, day 1 – 21) and random assignment (1:1, double blind) to oral C (320 mg twice daily, 4 days on/3 days off, from cycle 1, day 2) or matched placebo to disease progression. Primary endpoint: progression free survival (PFS; comprising PSA, radiographic or clinical progression, new cancer therapy or death; PCWG2 criteria) in the intent to treat (ITT) population. Secondary endpoints included overall survival (OS) and safety. PFS and OS were also assessed by composite biomarker (B) subgroup for PI3K/AKT/PTEN pathway activation status (NGS/IHC on archival tumour, contemporaneous ctDNA). Statistics: designed to detect a 50% increase in median PFS (6 to 9 months (mo)) between the placebo and C arms (90% power, 20% 1-sided alpha) by Cox proportional hazards model. Registration: ISRCTN 69139368. Results: 150 patients were randomised to 01/2019. Median follow up 16.77 months (IQR 12.0-26.5). PFS and OS by ITT and B status, are shown in the table (NR, not reached; CI confidence interval). Grade 3–4 adverse events (AE) were equally common between arms (62.2%). The most common AEs were diarrhoea, fatigue and nausea. Conclusions: Adding C to DP did not extend PFS. The OS secondary endpoint was significantly increased. PFS and OS results were consistent irrespective of PI3K/AKT/PTEN pathway activation status.
Description
Date
2020
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Crabb SJ, Griffiths GO, Marwood E, Dunkley D, Downs N, Martin K, et al. ProCAID: A randomized double-blind phase II clinical trial of capivasertib (C) in combination with docetaxel and prednisolone chemotherapy (DP) in metastatic castration-resistant prostate cancer (mCRPC). Journal of Clinical Oncology. 2020;38(15)