Study Stopped
Sponsor-PI decision. An analysis of the primary endpoint concluded that the addition of ribociclib to standard of care enzalutamide did not demonstrate benefit, an all active subjects were removed from the study.
Enzalutamide With Ribociclib in Treating Patients With Metastatic Castrate-Resistant, Chemotherapy Naive Prostate Cancer That Retains Retinoblastoma Expression
Phase IB/II Study of Enzalutamide With Ribociclib in Patients With Metastatic Castrate Resistant, Chemotherapy Naïve Prostate Cancer That Retains RB Expression
4 other identifiers
interventional
52
1 country
4
Brief Summary
This phase Ib/II trial studies the safety, side effects, best dose, and effectiveness of ribociclib when given with enzalutamide in treating patients with castrate-resistant prostate cancer that has spread from the primary site (place where it started) to other places in the body (metastatic), is chemotherapy naive, and retains retinoblastoma expression. Testosterone can cause the growth of prostate cancer cells. Hormone therapy using enzalutamide may fight prostate cancer by blocking the use of testosterone by the tumor cells. Ribociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Enzalutamide with ribociclib may be safe, tolerable and/or effective in treating metastatic, castrate-resistant, chemotherapy naive prostate cancer that retains retinoblastoma expression.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Dec 2015
Longer than P75 for phase_1
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 14, 2015
CompletedFirst Posted
Study publicly available on registry
September 21, 2015
CompletedStudy Start
First participant enrolled
December 1, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 7, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2023
CompletedResults Posted
Study results publicly available
April 22, 2026
CompletedApril 22, 2026
March 1, 2026
7 years
September 14, 2015
September 25, 2025
March 31, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Number of Dose Limiting Toxicity of Ribociclib (Phase IB)
Will be defined as an adverse event or clinically significant abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications. All analysis will be descriptive.
28 days
Number of Patients With a >= 50% Reduction in Prostate Specific Antigen (PSA) (Phase II)
The primary objective for the phase II component of this study is to determine efficacy with respect to the proportion of subjects that achieve a ≥ 50% reduction in PSA at 12 weeks.
12 weeks
Secondary Outcomes (3)
PSA Progression Free Survival (PFS)
Time of first dose until progression (25% increase in PSA from nadir) or death, assessed up to 2 years
Radiographic PFS (rPFS)
From first dose to disease progression in bone or soft-tissue, or death, whichever occurs first, assessed up to 40 months
Overall Survival
From first dose until death from any cause, assessed up to 60 months
Other Outcomes (3)
Number of Patients With RB Positive Tumors
Baseline
Number of Participants With Samples Where RB Status Can Successfully be Obtained
Baseline
Androgen Profiles
Up to 2 years
Study Arms (5)
Phase I: 200 mg Ribociclib + Enzalutamide
EXPERIMENTALEnzalutamide will be administered at a dose of 160 mg (40 mg X 4 pills) once daily. 200 mg Ribociclib will be given daily for 21 out of 28 days. The phase I portion of this study will follow a traditional 3+3 design, escalating to the next higher dose cohort if 3 patients are treated and no DLTs are observed in the first cycle of therapy.
Phase I: 400 mg Ribociclib + Enzalutamide
EXPERIMENTALEnzalutamide will be administered at a dose of 160 mg (40 mg X 4 pills) once daily. 400 mg Ribociclib will be given daily for 21 out of 28 days. The phase I portion of this study will follow a traditional 3+3 design, escalating to the next higher dose cohort if 3 patients are treated and no DLTs are observed in the first cycle of therapy.
Phase I: 600 mg Ribociclib + Enzalutamide
EXPERIMENTALEnzalutamide will be administered at a dose of 160 mg (40 mg X 4 pills) once daily. 600 mg Ribociclib will be given daily for 21 out of 28 days. The phase I portion of this study will follow a traditional 3+3 design, escalating to the next higher dose cohort if 3 patients are treated and no DLTs are observed in the first cycle of therapy.
Phase II: Enzalutamide Only
ACTIVE COMPARATORPatients receive Enzalutamide 160mg PO QD once daily on Days 1-28 of each 28-day cycle. This is one of two randomized arms in the Phase II portion. Treatment continues until disease progression or unacceptable toxicity. Patients also undergo blood sample collection, tumor biopsy, ECHO or MUGA, bone scan, and CT or MRI on study.
Ribociclib at RP2D + Enzalutamide
EXPERIMENTALPatients receive Ribociclib 600mg PO QD once daily on Days 1-21 of each 28-day cycle in combination with Enzalutamide 160mg PO QD once daily. This is one of two randomized arms in the Phase II portion. Patients will continue treatment until disease progression or unacceptable toxicity. Patients also undergo blood sample collection, tumor biopsy, ECHO or MUGA, bone scan, and CT or MRI on study.
Interventions
Given PO
Given PO
Correlative studies
Correlative studies
Undergo blood sample collection
Undergo tumor biopsy
Undergo ECHO
Undergo MUGA
Undergo bone scan
Undergo CT
Undergo MRI
Eligibility Criteria
You may qualify if:
- Willing and able to provide written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for the release of personal health information; NOTE: HIPAA authorization may be either included in the informed consent or obtained separately; consent and HIPPA authorization must be obtained prior to any screening procedures
- Histological or cytological proof of prostate cancer
- Documented progressive metastatic (m)CRPC based on at least one of the following criteria:
- PSA progression defined as 25% increase over baseline value with an increase in the absolute value of at least 2 ng/mL that is confirmed by another PSA level with a minimum of a 1 week interval and a minimum PSA of 2 ng/mL
- Soft-tissue progression defined as an increase \>= 20% in the sum of the longest diameter (LD) of all target lesions based on the smallest sum LD since treatment started or the appearance of one or more new lesions
- Progression of bone disease (evaluable disease) or (new bone lesion\[s\]) by bone scan
- Have testosterone \< 50 ng/dL; patients must continue primary androgen deprivation with an luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist) if they have not undergone orchiectomy
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Patients on long term (\> 6 months) anti-androgen therapy (e.g., flutamide, bicalutamide, nilutamide) will need to be off anti-androgen for 4 weeks (wash out period) and show evidence of disease progression off the anti-androgen; patients that have been on an anti-androgen 6 months or less will need to discontinue anti-androgen therapy prior to treatment start (no wash out period required)
- Absolute neutrophil count \>= 1.5 × 10\^9/L (obtained within 14 days prior to treatment start)
- Platelets (UNVPLT) \>= 100 x 10\^9/L (obtained within 14 days prior to treatment start)
- Hemoglobin (HGB) \>= 9 g/dl (obtained within 14 days prior to treatment start)
- Potassium (K) within normal limits for the institution or corrected to within normal limits with supplements before first dose of study medication (obtained within 14 days prior to treatment start)
- Total calcium (CA) (corrected for serum albumin) within normal limits for the institution or corrected to within normal limits with supplements before first dose of study medication (obtained within 14 days prior to treatment start)
- Magnesium within normal limits for the institution or corrected to within normal limits with supplements before first dose of study medication (obtained within 14 days prior to treatment start)
- +7 more criteria
You may not qualify if:
- Prior exposure to abiraterone acetate or other specific cytochrome P450 (CYP)-17 inhibitors; abiraterone acetate given in the castration-sensitive setting is permissible if stopped at least 6 months prior to initial protocol treatment
- Prior exposure to enzalutamide, apalutamide, or other investigational AR directed therapy
- Prior chemotherapy for castration resistant disease; chemotherapy given in the castration-sensitive setting is permissible if stopped at least 4 weeks prior to treatment start
- Prior isotope therapy with strontium-89, samarium or radium-223 within 12 weeks of treatment start
- Administration of antifungal agents (itraconazole, fluconazole, etc) within 4 weeks of treatment start or unrecovered adverse events (AEs) due to agents administered more than 4 weeks of treatment start
- History of pituitary or adrenal dysfunction, active or symptomatic viral hepatitis or chronic liver disease
- Known symptomatic brain metastases
- Use of any prohibited concomitant medications: immunotherapy, 5 alpha reductase inhibitors, spironolactone, diethystilbestrol (DES), ketoconazole, newer medications targeting ARs; NOTE: the concurrent use of all other drugs, over-the-counter medications, or alternative therapies must be documented; the principal investigator should be alerted if the patient is taking any agent that interacts with CYP450 system
- Treatment-related toxicity from prior therapy \> grade 2
- Peripheral neuropathy \>= 2
- History of hypersensitivity to ribociclib or compounds of similar chemical or biologic composition to ribociclib including to peanut and soy or other drugs formulated with polysorbate 80; or enzalutamide
- Currently taking any herbal, alternative or food supplements (i.e., prostate cancer \[PC\]-Spes, saw palmetto, St John wort, etc.); all herbal, alternative and food supplements must be discontinued prior to treatment start; patients may continue on a daily multi-vitamin, calcium and vitamin D
- Planned surgery or radiation therapy during protocol treatment
- Hormonal-acting agents (including DES, aldosterone, and spironolactone but not including gonadotropin-releasing hormone \[GnRH\] agonists or antagonists) are forbidden during the trial and must be stopped prior to treatment start; no washout period will be required for any of these agents
- Initiation of bisphosphonate/denosumab therapy during protocol treatment; patients on stable doses of bisphosphonates or denosumab which have been started no less than 4 weeks prior to treatment start may continue on this medication; NOTE: initiation of bisphosphonate/denosumab therapy will be allowed for the treatment of osteoporosis or prevention of skeletal-related events (SRE) during protocol treatment
- +33 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (4)
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- William Kevin Kelly, DO
- Organization
- Thomas Jefferson University
Study Officials
- PRINCIPAL INVESTIGATOR
William Kevin Kelly, MD
Thomas Jefferson University
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 14, 2015
First Posted
September 21, 2015
Study Start
December 1, 2015
Primary Completion
December 7, 2022
Study Completion
September 1, 2023
Last Updated
April 22, 2026
Results First Posted
April 22, 2026
Record last verified: 2026-03