Study of Pembrolizumab and Mifepristone in Patients With Advanced HER2-negative Breast Cancer

NCT03225547 | Terminated Phase 2 FDA Drug

• 1 other identifier: IRB17-0721
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase II study of pembrolizumab plus mifepristone in advanced breast cancer patients. The study will include a safety lead in of ten patients. Patients who are deemed eligible and have signed informed consent will be treated with pembrolizumab at a fixed dose of 200 mg intravenously on day 1 of each 21 day cycle for each dose level. Mifepristone 300mg PO be administered daily starting the week prior to pembrolizumab. Once the safety of the combination is confirmed (study will be paused at least 6 weeks after first 10 patients are enrolled for safety evaluation), dose expansion cohorts will be performed in parallel for two cohorts: cohort 1 in triple-negative breast cancer and cohort 2 in hormone receptor positive breast cancer.

Conditions

Triple Negative Breast Neoplasms; Breast Cancer

Keywords

breast cancer; pembrolizumab; mifepristone

Outcome Measures

Primary Outcomes (1)

• Rate of overall response based on RECIST 1.1

  Determine the overall response rate (ORR) based on RECIST 1.1 of the combination of pembrolizumab and mifepristone in the different subtypes of breast cancer (hormone receptor positive and triple-negative)

  From the time of first documented complete response or appearance of one or more new lesions, until the first documented date of recurrent or progressive disease, whichever came first, assessed up to 100 months.

Secondary Outcomes (2)

• Number of patients with adverse events

  Up to 3 years

• Rate of overall response based on irRECIST

  From the time of first documented complete response or appearance of one or more new lesions, until the first documented date of recurrent or progressive disease, whichever came first, assessed up to 100 months.

Study Arms (2)

Cohort 1

EXPERIMENTAL

Enrollment will be paused after the first 10 patients are enrolled in the study for a safety evaluation. Once safety is confirmed, patients with hormone receptor positive, hormone refractory advanced breast cancer will be enrolled in cohort 1. Regardless of cohort, all eligible patients will be treated with pembrolizumab (on day 1 of every 21 day cycle), and mifepristone (administered daily starting the week prior to pembrolizumab).

Drug: Pembrolizumab; Drug: Mifepristone

Cohort 2

EXPERIMENTAL

Enrollment will be paused after the first 10 patients are enrolled in the study for a safety evaluation. Once safety is confirmed, patients with triple-negative advanced breast cancer will be enrolled in cohort 2. Regardless of cohort, all eligible patients will be treated with pembrolizumab (on day 1 of every 21 day cycle), and mifepristone (administered daily starting the week prior to pembrolizumab).

Drug: Pembrolizumab; Drug: Mifepristone

Interventions

Pembrolizumab DRUG

Pembrolizumab 200mg will be administered to all patients on day 1 of every 21 day cycle.

Also known as: Keytruda

Cohort 1; Cohort 2

Mifepristone DRUG

Mifepristone 300mg will be administered to all patients daily starting the week prior to pembrolizumab.

Also known as: Mifeprex

Cohort 1; Cohort 2

Eligibility Criteria

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

You may qualify if:

• Common to both cohorts
• Patients must have histologically confirmed breast cancer that is metastatic or locally advanced and unresectable.
• Patients must have evaluable disease as defined by RECIST 1.1 with tumor lesion \> 10 mm by CT scan or caliper measurement on clinical exam or lymph node ≥ 15mm in short axis.
• ECOG performance status of 0 or 1.
• Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of pembrolizumab in combination with mifepristone in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
• Patients must have normal organ and marrow function as defined below:
• absolute neutrophil count ≥ 1,000/mcL
• platelets ≥ 80,000/mcL
• total bilirubin within normal institutional limits
• AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional upper limit of normal
• creatinine clearance ≥ 60 mL/min/1.73 m2
• INR ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use on anticoagulant.
• Females of child-bearing potential (defined as a sexually mature woman who has not undergone hysterectomy, bilateral oophorectomy, or who has not been naturally postmenopausal for at least 24 consecutive months prior to study enrollment) must:
• Commit to abstinence from heterosexual contact or agree to use effective contraception without interruption beginning at least 28 days prior to starting protocol therapy, while on study medication, and for 6 months following the last dose of therapy.
• Have a negative serum pregnancy test (β -hCG) result at screening.

You may not qualify if:

• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
• Patients who have had chemotherapy or radiotherapy prior to entering the study must have recovered from adverse events to Grade 1. Radiation within 3 months of study treatment initiation is prohibited, as serious rashes have been observed in patients who have recently received radiation therapy.
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 agent, or mifepristone
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging at least 4 weeks prior to first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to treatment.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab or mifepristone
• Uncontrolled intercurrent medical or psychiatric illness that would limit compliance with study requirements.
• Pregnant women are excluded from this study because Mifepristone is an abortifacient agent with the potential for teratogenic effects.
• Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Mifepristone, breastfeeding should be discontinued if the mother wishes to participate in this study.
• HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with pembrolizumab and/or mifepristone. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has evidence of active, non-infectious pneumonitis
• Has an active infection requiring intravenous systemic therapy
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to first dose of therapy. Administration of killed vaccines is allowed.
• Has a known human immunodeficiency virus (HIV), known active Hepatitis B (e.g. HBsAg reactive), or Hepatitis C (e.g. HCV RNA \[qualitative\] is detected) infection.

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

University of Chicago

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

pembrolizumab; Mifepristone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Rita Nanda, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The first 10 patients will receive the same treatment. Enrollment will be paused to undergo a safety evaluation. After which, enrollment will continue and two cohorts will be preformed in parallel.

Study Record Dates

• First Submitted: July 17, 2017
• First Posted: July 21, 2017
• Study Start: February 12, 2018
• Primary Completion: September 30, 2025
• Study Completion: September 30, 2025
• Last Updated: December 23, 2025

Record last verified: 2025-12

Locations

US (1)