- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03650894
Nivolumab, Ipilimumab, and Bicalutamide in Human Epidermal Growth Factor (HER) 2 Negative Breast Cancer Patients
A Phase II Study of Nivolumab Combined With Bicalutamide and Ipilimumab in Metastatic HER2-negative Breast Cancer
Study Overview
Status
Intervention / Treatment
Detailed Description
This is a phase II trial to assess the clinical efficacy and safety of nivolumab (anti-Programmed Death receptor-1, or anti-PD-1) combined with bicalutamide (Androgen Receptor (AR) inhibitor) and ipilimumab (anti-cytotoxic T-lymphocyte-associated protein 4, or anit-CTLA4) in patients with advanced breast cancer.
This study will include adult women with metastatic or locally advanced unresectable Human Epidermal Growth Factor (HER2)-negative breast cancer (by National Comprehensive Cancer Network (NCCN) criteria). Triple-negative breast cancer tumors will require confirmation of AR positivity at screening. Participants will have had no more than one line of previous chemotherapy in non-curative setting; subjects with metastatic progression within 1 year following completion of curative-intent chemotherapy are eligible if they have not received any additional lines of systemic therapy in the non-curative setting.
Women who meet all of the study inclusion criteria, none of the study exclusion criteria, and agree to participate will receive a combination of the following:
- Intravenous nivolumab 240mg, every 2 weeks until progression or unacceptable toxicity
- Intravenous ipilimumab 1mg/kg, every 6 weeks until progression or unacceptable toxicity
- Oral bicalutamide 150mg, daily until progression or unacceptable toxicity
Participants are to be treated for up to 24 months. Patients who have ongoing response will discontinue ipilimumab and nivolumab after 24 months, but at the discretion of the investigator may continue bicalutamide, and will continue assessments as per standard of care. Any patient who subsequently progresses will have the option to resume treatment upon disease progression.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Larisa Lundgren
- Phone Number: (503) 215-2614
- Email: Larisa.Lundgren@providence.org
Study Contact Backup
- Name: Nicole Moxon, RN
- Phone Number: (503) 215-2619
- Email: Nicole.Moxon@providence.org
Study Locations
-
-
New York
-
New York, New York, United States, 10065
- Memorial Sloan Kettering Cancer Center
-
-
Oregon
-
Portland, Oregon, United States, 97213
- Providence Oncology & Hematology Care Clinic - Eastside
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- ECOG performance status of 0-1;
- Metastatic or locally advanced unresectable HER2-negative breast cancer (by NCCN criteria);
- Triple Negative Breast Cancer tumors will require confirmation of androgen-receptor (AR) positivity at screening (refer to laboratory manual for guidelines). Local testing permitted for eligibility if reviewed by a designated study pathologist;
- RECIST1.1 measurable disease;
- Participants must be willing (if clinically feasible) to provide a fresh tumor biopsy (or archived tissue). For archived tissue, a tissue block from the most recent biopsy is acceptable if no intervening anti-neoplastic therapies have been administered since the time of biopsy.
- Previous systemic chemotherapy: no greater than one line of previous chemotherapy in non-curative setting; subjects with metastatic progression within 1 year following completion of curative-intent chemotherapy are eligible if they have not received any additional lines of systemic therapy in the non-curative setting.
- Participants must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal patient care.
- Participants must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, tumor biopsies, and other requirements of the study
- Adequate hematologic and liver function (using CTCAE v4). (All baseline laboratory requirements will be assessed and should be obtained within 14 days prior to enrollment): WBC≥2000/μL; Neutrophils≥1500/μL; Platelets≥100 × 103/μL; Hemoglobin ≥9.0 g/dL; AST≤3 × ULN; ALT ≤3 × ULN; Total bilirubin ≤1.5 × ULN (except in participants with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL). Subjects with elevations in LFTs related to underlying hepatic cancer involvement may be considered for enrollment (after discussion with lead PI) if ALT/AST is ≤5 x ULN and Total bilirubin ≤3 × ULN.
- Female and Age ≥18 years. (Men are excluded because of potential confounding effects of sex on correlative analyses)
- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study treatment.
- Women must not be breastfeeding
- Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of birth regulation for the duration of treatment with study treatment(s) for a total of 5 months post-treatment completion.
Exclusion Criteria:
- Active brain metastases or leptomeningeal metastases. Participants with brain metastases are eligible if these have been treated and there is no magnetic resonance imaging (MRI except where contraindicated in which CT scan is acceptable) evidence of progression for at least 2 weeks after treatment is complete and within 28 days prior to first dose of study drug administration. Cases must be discussed with the lead PI, Dr. Page. Brain lesions are not considered measurable disease.
- Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, or carcinoma in situ of the cervix. Subjects with prior history of unrelated breast cancer not requiring active therapy may be considered for enrollment, but require discussion with and approval of PI;
- Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the participant to receive protocol therapy, or interfere with the interpretation of study results.
- Participants must have recovered from the effects of major surgery requiring general anesthetic or significant traumatic injury at least 14 days before enrollment.
- Participants with active, known or suspected autoimmune disease. Participants with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
- Uncontrolled adrenal insufficiency.
- New York Heart Association (NYHA) Functional Classification of Heart Failure: Class III or Class IV
- All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to Grade 1 (NCI CTCAE version 4) or baseline before administration of study drug. Participants with toxicities attributed to prior anti-cancer therapy which are not expected to resolve and result in long lasting sequelae, such as peripheral neuropathy grade 2 or less, are permitted to enroll
- Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, or psychiatric illness/social situations that would limit obtaining informed consent or compliance with study requirements.
- Participants who have had a history of acute diverticulitis, intra-abdominal abscess, GI obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation.
- Participants with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
- Has known active hepatitis B (e.g. HBsAg reactive) or Hepatitis C (e.g. HCV RNA is detected);
- History of allergy or hypersensitivity to study drug components
- Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody in the metastatic setting, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. Previous treatment with anti-PD-1/L1 in the curative setting is allowed if subjects have not received such therapy within one year of screening.
- Prior treatment with bicalutamide, enzalutamide, or any other androgen receptor blocker.
- Use of an investigational agent within 4 weeks of Day 1 visit
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Nivolumab, Ipilimumab, and bicalutamide
Participants will receive nivolumab plus ipilimumab combination therapy.
Participants should receive nivolumab at a dose of 240 milligrams (mg) fixed dose as a 30-minute intravenous (IV) infusion prepared in 50 milliliter (ml) normal saline (NS) every 2 weeks until progression.
Participants should receive ipilimumab at a dose of 1 mg/kilogram as a 30-minute IV infusion prepared in 50 ml NS every 6 weeks.
All subjects will take bicalutamide 150mg (3 x 50mg tablets) daily.
|
Nivolumab 240 mg IV every 2 weeks
Other Names:
Ipilimumab 1 mg/kg IV every 6 weeks.
Other Names:
Oral bicalutamide 150mg (3 x 50mg tablets) daily
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
iRECIST Clinical Benefit Rate (the number of patients with objective response or ongoing stable disease at week 24 using iRECIST guidelines)
Time Frame: 24 weeks
|
To assess the 24-week clinical benefit rate of nivolumab combined with bicalutamide and ipilimumab in advanced HER2-negative breast cancers assessed by radiographic criteria (computed tomography (CT) scan or magnetic resonance imaging (MRI) according to iRECIST criteria.
|
24 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Assess best overall objective response rate (proportion of patients who achieve a complete or partial response)
Time Frame: 24 months
|
Best overall objective response rate will be assessed by radiographic criteria from CT or MRI scans and will be based on RECIST 1.1 and iRECIST criteria
|
24 months
|
Duration of progression free survival
Time Frame: From first patient enrolled through last patient's progression or 24 months following last patient enrolled, whichever comes first.
|
Average length of time between study entry and disease progression or death
|
From first patient enrolled through last patient's progression or 24 months following last patient enrolled, whichever comes first.
|
Overall survival rate
Time Frame: 24 months.
|
Number of patients who are alive
|
24 months.
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: David B. Page, MD, Providence Health & Services
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Immunological
- Hormone Antagonists
- Immune Checkpoint Inhibitors
- Androgen Antagonists
- Nivolumab
- Bicalutamide
- Ipilimumab
Other Study ID Numbers
- CA209-8H3
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Breast Cancer
-
Northwestern UniversityEisai Inc.UnknownMale Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-negative Breast Cancer | Progesterone Receptor-negative Breast Cancer | HER2-negative...United States
-
University of Southern CaliforniaNational Cancer Institute (NCI)WithdrawnStage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast Cancer
-
Rutgers, The State University of New JerseyNational Cancer Institute (NCI); Rutgers Cancer Institute of New JerseyActive, not recruitingStage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-negative Breast Cancer | Progesterone Receptor-negative Breast Cancer | HER2-negative Breast CancerUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)TerminatedMale Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast CancerUnited States
-
University of California, IrvineNational Cancer Institute (NCI); National Institutes of Health (NIH)CompletedBreast Cancer | HER2-positive Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast Cancer | HER2-negative Breast CancerUnited States
-
University of WashingtonNational Cancer Institute (NCI)CompletedHER2-positive Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-positive Breast CancerUnited States
-
Joseph Baar, MD, PhDCompletedBreast Cancer | Stage I Breast Cancer | Inflammatory Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IIIC Breast CancerUnited States
-
Baylor Breast Care CenterRecruitingBreast Cancer | Breast Neoplasm | Triple Negative Breast Cancer | Triple Negative Breast Neoplasms | HER2-positive Breast Cancer | Breast Cancer Stage II | Breast Cancer Female | Breast Cancer Stage III | Estrogen Receptor-positive Breast Cancer | Hormone Receptor-positive Breast Cancer | Breast Cancer InvasiveUnited States
-
Innocrin PharmaceuticalCompletedBreast Cancer | Advanced Breast Cancer | Metastatic Breast Cancer | Triple Negative Breast Cancer | Male Breast Cancer | ER+ Breast Cancer | Cancer of the BreastUnited States
-
University of WashingtonTerminatedBreast Cancer | Breast Cancer Stage I | Breast Cancer Stage II | Breast Cancer Stage III | Breast Cancer Stage IIB | Breast Cancer Stage IIA | Breast Cancer Stage IIIA | Breast Cancer Stage IIIB | Breast Cancer Stage IIIcUnited States
Clinical Trials on Nivolumab
-
Universitair Ziekenhuis BrusselNot yet recruiting
-
Brown UniversityBristol-Myers Squibb; The Miriam Hospital; Rhode Island Hospital; Women and Infants...Terminated
-
Bristol-Myers SquibbRecruitingMelanomaSpain, United States, Italy, Chile, Greece, Argentina
-
Baptist Health South FloridaBristol-Myers Squibb; NovoCure Ltd.TerminatedRecurrent GlioblastomaUnited States
-
HUYABIO International, LLC.Bristol-Myers SquibbRecruitingUnresectable or Metastatic Melanoma | Progressive Brain MetastasisSpain, United States, Italy, Japan, Belgium, France, New Zealand, Brazil, Korea, Republic of, Australia, Germany, Singapore, Czechia, Austria, South Africa, United Kingdom, Puerto Rico
-
Michael B. Atkins, MDBristol-Myers Squibb; Hoosier Cancer Research NetworkActive, not recruitingAdvanced Renal Cell CarcinomaUnited States
-
Jason J. Luke, MDArray BioPharmaActive, not recruitingMelanoma | Renal Cell Carcinoma | Solid Tumor | Non-small Cell Lung Cancer | Head and Neck Squamous Cell CarcinomaUnited States
-
Bristol-Myers SquibbCompletedLung CancerItaly, United States, France, Russian Federation, Spain, Argentina, Belgium, Brazil, Canada, Chile, Czechia, Germany, Greece, Hungary, Mexico, Netherlands, Poland, Romania, Switzerland, Turkey, United Kingdom
-
National Health Research Institutes, TaiwanNational Taiwan University Hospital; Mackay Memorial Hospital; China Medical... and other collaboratorsRecruitingHepatocellular Carcinoma (HCC)Taiwan
-
IRCCS San RaffaeleBristol-Myers SquibbRecruiting