LEE011 (Ribociclib) in Combination With Docetaxel Plus Prednisone in mCRPC

Conditions

• Prostate Cancer

Eligibility Criteria

Sex

MALE

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Docetaxel-PNP — DRUG
  Given IV
• Ribociclib — DRUG
  Given Orally
• Prednisone — DRUG
  Given Orally
• Filgrastim — DRUG
  Given IV

Study Details

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.

Key Dates

Start date

Nov 20, 2015

Status verified

Aug 2022

Primary completion

Jul 30, 2021

Completion

Jul 30, 2021

Study Design

Enrollment

43 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Treatment (Phase 1b)
  The starting cohort dose level (1) for docetaxel will be 75 mg/m2, administered on day 1 of each cycle. Prednisone will be fixed at 5 mg twice a day. The starting dose level and schedule for ribociclib will begin at 200 mg orally once daily, starting on day 1 of the 21-day cycle. If dose level 1 is not tolerated, then alternative dosing schedules of docetaxel will be evaluated, starting with dose level 1A of 60mg/m2 docetaxel.
• Experimental: Treatment (Phase 2)
  Participants in Phase 2 will receive the Recommended Phase 2 Dose for docetaxel and ribociclib

Primary Outcome Measure

Maximally Tolerated Dose (MTD) (Phase 1b) [ Time Frame: Up to 2 years ]

Locations (6)

Find similar trials in San Francisco, CA

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