LEE011 (Ribociclib) in Combination With Docetaxel Plus Prednisone in mCRPC
Status:
Completed
Trial end date:
2021-07-30
Target enrollment:
Participant gender:
Summary
This is a Phase Ib/II open label clinical trial in patients with metastatic castration
resistant prostate cancer. The objective of the phase Ib portion of the study is to establish
the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of docetaxel (75 mg/m2 IV
q21 days) and prednisone (5mg orally BID) in combination with ribociclib in escalating oral
daily doses in patients with metastatic castrate resistant prostate cancer (mCRPC) with prior
resistance to abiraterone and/or enzalutamide who have not undergone prior chemotherapy for
metastatic disease. Up to three cohorts will be enrolled to determine the MTD and DLT profile
of this combination during Phase 1b. Dose escalation will follow the standard 3+3 design. The
dosing schedule is being chosen to allow patients to be exposed to the most efficacious
dosing schedule of docetaxel (75 mg/m2 every 3 weeks). If there is excess toxicity observed
with the treatment combination at the first dose level (dose level I), an alternative dosing
schema may be pursued with weekly docetaxel treatment (35 mg/m2 weekly), which has
demonstrated activity in mCRPC and decreased risk of cytopenias compared with every 3 week
dosing schedule.
The Phase II portion (N = 29) of the study is a single arm, two stage, open-label study of
ribociclib (dosed at the RP2D) in combination with docetaxel and prednisone to determine the
efficacy and further define the safety of the treatment combination. Patients will be treated
with the combination of ribociclib plus docetaxel + prednisone for up to 9 cycles. If there
is no evidence of radiographic or clinical disease progression after 9 cycles of protocol
therapy, patients may continue on single agent maintenance ribociclib until the time of
disease progression. Patients will have the option of starting maintenance ribociclib after 6
cycles of docetaxel if stable disease or better on re-staging scans. The dose of ribociclib
used during maintenance will be the same dose as that immediately preceding cessation of
docetaxel treatment.