Clinical trial NCT02494921: LEE011 (Ribociclib) in Combination With Docetaxel Plus Prednisone in mCRPC
Official title: A Phase 1b/2 Study of the Oral CDK4/6 Inhibitor LEE011 (Ribociclib) in Combination With Docetaxel Plus Prednisone in Metastatic Castration Resistant Prostate Cancer
Conditions: Prostate Cancer
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.
Interventions:
description: Given IV
name: Docetaxel-PNP
other_name: Docetaxel Injection
Taxotere
type: Drug
description: Given Orally
name: Ribociclib
other_name: Kisqali
type: Drug
description: Given Orally
name: Prednisone
other_name: Prednisone Oral
type: Drug
description: Given IV
name: Filgrastim
other_name: Neupogen
type: Drug
Study arms:
design_group_description: 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.
design_group_title: Treatment (Phase 1b)
design_group_type: Experimental
design_group_description: Participants in Phase 2 will receive the Recommended Phase 2 Dose for docetaxel and ribociclib
design_group_title: Treatment (Phase 2)
design_group_type: Experimental
Sponsor: The University of California, San Francisco
Collaborators: Novartis AG
Drug name mappings:
name: 琥珀酸瑞波西利
lang: CN
name: Ribociclib Succinate
lang: EN
name: 泼尼松
lang: CN
name: Prednisone
lang: EN
name: 非格司亭 （安进）
lang: CN
name: Filgrastim (Amgen)
lang: EN
name: フィルグラスチム（遺伝子組換え）
lang: JP
name: 多西他赛
lang: CN
name: Docetaxel
lang: EN
name: ドセタキセル
lang: JP