Ribociclib and Bicalutamide in AR+ TNBC

NCT03090165 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: BTCRC BRE15-024
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 6

Brief Summary

This is an open label, multi-institutional, single arm phase II trial of ribociclib in combination with bicalutamide in advanced AR+ triple-negative breast cancer. No randomization or blinding is involved.

Conditions

Triple Negative Breast Cancer

Keywords

Triple Negative Breast Neoplasms; ribociclib; LEE011; CDK 4/6 inhibitor; bicalutamide

Outcome Measures

Primary Outcomes (2)

• Phase I: Maximum Tolerated Dose

  Phase I: Maximum tolerated dose (MTD) for subjects receiving ribociclib and bicalutamide without experiencing dose-limiting toxicity(s) (DLT) per Common Terminology Criteria for Adverse Events (CTCAE) v4

  D1 of treatment to end of cohort cycle (assessed at 28 days)

• Phase II: Clinical benefit rate (CBR) of treatment combination

  Compare sum of confirmed complete plus partial responses plus stable disease per response evaluation criteria in solid tumors (RECIST) 1.1 criteria

  D1 of treatment to end of 4 treatment cycles (assessed at 16 weeks)

Secondary Outcomes (9)

• Phase I: Objective Response Rate (ORR)

  2 years

• Phase I: Duration of Response

  2 years

• Phase I: Assess Safety and Tolerability By summarizing counts and percentages grade 3-5 adverse events (NCI CTCAE Version 4)

  2 years

• Phase I: Ribociclib pharmacokinetics

  2 months

• Phase II: Progression Free Survival (PFS)

  2 years

Study Arms (1)

Arm A - Phase I

EXPERIMENTAL

Dose Escalation Cohort 1 will consist of 3-6 patients who will receive bicalutamide 150mg PO daily on days 1-28 of a 28 day cycle and ribociclib 400mg PO daily on days 1-21 of a 28 day cycle. Cohort 2 will consist of 3-6 patients who will receive bicalutamide 150mg PO daily on days 1-28 of a 28 day cycle and ribociclib 400mg PO daily on days 1-28 of a 28 day cycle. Cohort 3 will consist of 3-6 patients who will receive bicalutamide 150mg PO daily on days 1-28 of a 28 day cycle and ribociclib 600mg PO daily on days 1-21 of a 28 day cycle. Experimental: Arm B - Phase II Investigational Treatment The maximum safe dose of ribociclib in combination with bicalutamide will be given to up to 25 patients.

Drug: ribociclib; Drug: Bicalutamide

Interventions

ribociclib DRUG

400mg PO

Also known as: LEE011

Arm A - Phase I

Bicalutamide DRUG

150mg PO

Arm A - Phase I

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological or cytological confirmed, metastatic or unresectable triple-negative breast cancer (TNBC). TNBC will be defined as expression of ER\<10%, PR\< 10% and HER2 negative either by IHC (0, 1+ are negative, 2+ equivocal) or in situ hybridization method (ratio \<2.0 is negative).
• Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Up to 3 prior line of systemic therapy for metastatic disease is allowed. Combination therapy will be considered 1 line.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0, 1 or 2 within 28 days prior to registration.
• Life expectancy of \> 12 weeks as determined by the treating physician.
• Measurable disease according to RECIST 1.1 within 28 days prior to registration.
• No active central nervous system (CNS) metastatic disease. NOTE: Subjects with CNS involvement must meet ALL of the following to be eligible:
• At least 28 days from prior definitive treatment of their CNS disease by surgical resection, stereotactic body radiation therapy (SBRT) or whole brain radiation treatment (WBRT) at the time of registration
• AND asymptomatic and off systemic corticosteroids and/or enzyme-inducing anti-epileptic medications for brain metastases for \>14 days prior to registration.
• Prior cancer treatment must be completed at least 14 days prior to registration and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to ≤grade 1 or to baseline prior to initiation of that therapy.
• Screening rate-corrected QT interval (QTc) must be \<450msec and a resting heart rate of at least 50-90 bpm via a standard 12-lead ECG within 28 days prior to registration.
• Demonstrate adequate bone marrow and organ function as defined in the protocol; all screening labs to be obtained within 28 days prior to registration.
• Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), or they are naturally postmenopausal for at least 12 consecutive months, or her male partner has had a vasectomy at least 6 months prior to screening (The sterilized male partner must be her only sexual partner.).
• Females of childbearing potential and males must be willing to abstain from heterosexual activity or must agree to use adequate contraception (hormonal or barrier method) for the duration of study participation and for 3 weeks after discontinuation of study treatment.

You may not qualify if:

• Prior therapy with AR antagonists including but not limited to bicalutamide, enzalutamide, abiraterone and orteronel.
• Prior therapy with any CDK 4/6 inhibitors with the exception of participation in a window or preoperative study for Stage I-III operable breast cancer..
• Active infection requiring systemic therapy.
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• Known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least three years.
• Treatment with any investigational drug within 14 days prior to registration or within 5 half-lives of the investigational product, whichever is longer. Immunotherapies such as PD-L1 or PD-1 inhibitors only require a 14 day window, regardless of half-life. Investigational imaging agents are not included in this definition and are allowed.
• Subject who has received radiotherapy \<14 days prior to registration, and who has not recovered to grade 1 or better from related side effects of such therapy (exceptions include alopecia and any adverse events deemed by the investigator to be unlikely to interfere with the study drug safety).
• Subject has had major surgery within 14 days prior to registration or has not recovered from major side effects of the surgery (tumor biopsy is not considered as major surgery).
• Known hypersensitivity to any of the excipients of ribociclib or bicalutamide.
• Any impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
• Known history of HIV infection (testing not mandatory).
• Any concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate subject participation in the clinical study or compromise compliance with the protocol (e.g. chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled fungal, bacterial or viral infections, etc.).
• Subjects with any of the following conditions are excluded:
• Serious or non-healing wound, ulcer, or bone fracture.
• History of abdominal fistula, gastrointestinal perforation, or intra- abdominal abscess within 28 days prior to registration.

Sponsors & Collaborators

• Kari Wisinski: lead
• Novartis: collaborator
• Big Ten Cancer Research Consortium: collaborator
• University of Wisconsin, Madison: collaborator

Study Sites (6)

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

Location

Michigan State University

Lansing, Michigan, 48910, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Penn State Cancer Institute

Hershey, Pennsylvania, 17033, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Related Links

• Big Ten Cancer Research Consortium Website

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

ribociclib; bicalutamide

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Kari Wisinski, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: March 1, 2017
• First Posted: March 24, 2017
• Study Start: May 7, 2018
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: January 2, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)