Breast Neoplasm FemalePhase 2NCT03650894
Nivolumab, Ipilimumab, and Bicalutamide in Human Epidermal Growth Factor (HER) 2 Negative Breast Cancer Patients
A Phase 2 study testing Nivolumab, Ipilimumab and Bicalutamide in people with Breast Neoplasm Female and Breast Cancer, run by Providence Health & Services at 2 sites in United States.
Trial summary
The goal of this protocol is to evaluate the safety and efficacy of an alternative systemic combination approach that omits or delays the use of chemotherapy in metastatic disease, while improving efficacy and durability of response. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Neoplasm Female, Breast Cancer, Breast Carcinoma
- What is being tested?
- Nivolumab, Ipilimumab and Bicalutamide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesUnited States
- Study dates
- 3 Apr 2019to Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Providence Oncology & Hematology Care Clinic - Eastside
Portland, Oregon, 97213
About this study
Official title: A Phase II Study of Nivolumab Combined With Bicalutamide and Ipilimumab in Metastatic HER2-negative Breast Cancer
The goal of this protocol is to evaluate the safety and efficacy of an alternative systemic combination approach that omits or delays the use of chemotherapy in metastatic disease, while improving efficacy and durability of response. The approach combines two potentially effective and previously studied strategies: androgen receptor blockade and immune checkpoint therapy.
Read the 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.
- Conditions
- Breast Neoplasm Female, Breast Cancer, Breast Carcinoma, Breast Tumor
- Being tested
- Nivolumab, Ipilimumab, Bicalutamide
- Keywords
- Breast Cancer, Her2 negative breast cancer, Immunotherapy, Opdivo, Nivolumab, Yervoy, Ipilimumab, Bicalutamide, Casodex
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called Opdivo
Nivolumab 240 mg IV every 2 weeks
IpilimumabDrug
Also called Yervoy
Ipilimumab 1 mg/kg IV every 6 weeks.
BicalutamideDrug
Also called Casodex
Oral bicalutamide 150mg (3 x 50mg tablets) daily
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab, Ipilimumab, and bicalutamide | Experimental | 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. Receives: Drug: Nivolumab; Drug: Ipilimumab; Drug: Bicalutamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
iRECIST Clinical Benefit Rate (the number of patients with objective response or ongoing stable disease at week 24 using iRECIST guidelines)
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.
Measured: 24 weeks
Secondary outcomes (3)
Assess best overall objective response rate (proportion of patients who achieve a complete or partial response)
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
Measured: 24 months
Duration of progression free survival
Average length of time between study entry and disease progression or death
Measured: From first patient enrolled through last patient's progression or 24 months following last patient enrolled, whichever comes first.
Overall survival rate
Number of patients who are alive
Measured: 24 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2018
- Study start3 Apr 2019
- Primary completion10 Mar 2023
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast Neoplasm FemaleStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a phase II open-label study of nivolumab combined with ipilimumab and bicalutamide for HER2-negative metastatic or unresectable breast cancer.
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Providence Health & Services
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb, Memorial Sloan Kettering Cancer Center
- Responsible party
- Sponsor
- Investigators
- David B. Page, MD, Principal investigator, Providence Health & Services
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03650894
- Sponsor's protocol ID
- CA209-8H3
- Status last verified
- Apr 2026
- First submitted
- 27 Aug 2018
- Last updated
- 13 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Nivolumab Combined With Bicalutamide and Ipilimumab in Metastatic HER2-negative Breast Cancer
- ClinicalTrials.gov ID
- NCT03650894
- Acronym / sponsor ID
- CA209-8H3
- Conditions
- Breast Neoplasm Female, Breast Cancer, Breast Carcinoma, Breast Tumor
- Keywords
- Breast Cancer, Her2 negative breast cancer, Immunotherapy, Opdivo, Nivolumab, Yervoy, Ipilimumab, Bicalutamide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Providence Health & ServicesUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb, Memorial Sloan Kettering Cancer Center
- Study start
- 3 Apr 2019 (actual)
- Primary completion
- 10 Mar 2023 (actual)
- Study completion
- Dec 2026 (estimated)
- First posted
- 29 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this protocol is to evaluate the safety and efficacy of an alternative systemic combination approach that omits or delays the use of chemotherapy in metastatic disease, while improving efficacy and durability of response. The approach combines two potentially effective and previously studied strategies: androgen receptor blockade and immune checkpoint therapy.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a phase II open-label study of nivolumab combined with ipilimumab and bicalutamide for HER2-negative metastatic or unresectable breast cancer.
| Arm | Type | Receives |
|---|---|---|
| Nivolumab, Ipilimumab, and bicalutamide | Experimental | Drug: Nivolumab, Drug: Ipilimumab, Drug: BicalutamideParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NivolumabAlso: OpdivoNivolumab 240 mg IV every 2 weeks | Drug | Nivolumab, Ipilimumab, and bicalutamide |
| IpilimumabAlso: YervoyIpilimumab 1 mg/kg IV every 6 weeks. | Drug | Nivolumab, Ipilimumab, and bicalutamide |
| BicalutamideAlso: CasodexOral bicalutamide 150mg (3 x 50mg tablets) daily | Drug | Nivolumab, Ipilimumab, and bicalutamide |
Primary outcome
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.
3 secondary outcomes
Assess best overall objective response rate (proportion of patients who achieve a complete or partial response)
Time frame: 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.
Overall survival rate
Time frame: 24 months.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2026.
- Providence Cancer InstituteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David B. Page, MD principal investigator
Providence Health & Services
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab, Ipilimumab and Bicalutamide in people with Breast Neoplasm Female and Breast Cancer, run by Providence Health & Services at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 13 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2026.