A Study of Anti-PD-1 (Pembrolizumab) + Hormonal Therapy in HR-positive Localized IBC Patients With Non-pCR to Neoadjuvant Chemotherapy

• Status: Not yet recruiting
• Trial end date: 0000-00-00
• Target enrollment: 37
• Participant gender: Both

Summary

The goal of this clinical research study is to learn if pembrolizumab in combination with standard hormone therapy can help to control and prevent inflammatory breast cancer (IBC). The safety of this drug combination will also be studied.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Pembrolizumab
• Last Updated: 2016-11-22

Criteria

Inclusion Criteria:

1. Is willing and able to provide written informed consent for the trial.

2. Is a female or male and >/= 18 years of age

3. Has histological confirmation of breast carcinoma.

4. Has confirmed inflammatory breast cancer by using international consensus criteria:

(1) Onset: Rapid onset of breast erythema, edema and/or peau d'orange, and/or warm breast, with/without an underlying breast mass. (2) Duration: History of such findings no more than 6 months (3) Extent: Erythema occupying at least 1/3 of whole breast. (4) Pathology: Pathologic confirmation of invasive carcinoma

5. Did not achieve pathological complete response (pCR) to any chemotherapy that was given with the intention to induce best response prior surgery. pCR is defined as the current American Joint Committee on Cancer (AJCC) breast cancer staging

6. Is HER2 normal, defined as HER2 0 or 1+ by IHC and negative by FISH if performed; or HER2 is 2+ by IHC and negative by FISH; or HER2 negative by FISH if IHC is not performed.

7. Has positive ER or PR status. ER or PR >/= 10%

8. Has a performance status of 0-1 on the ECOG Performance Scale.

9. Has adequate organ function as determined by the following laboratory values: ANC >/= 1,500 /mcL, Platelets >/=100,000 /mcL, Hgb >/= 9 g/dL, creatinine levels < 1.5 x ULN, Total bilirubin

10. Subjects of reproductive potential must agree to avoid becoming pregnant or impregnating a partner, respectively, while receiving study drug and for 120 days after the last dose of study drug by complying with one of the following: (1) practice abstinence† from heterosexual activity; OR (2) use (or have their partner use) acceptable contraception during heterosexual activity.

11. Has negative serum or urine pregnancy test for subjects of childbearing potential within 10 days before first dose.

12. If patient has already started hormonal blockade therapy after radiation as adjuvant therapy, patient is eligible as long as the patient has been on hormonal blockade therapy within 2 months by the time of screening and can start the study drug within 4 weeks since the completion of screening

Exclusion Criteria:

1. Is currently participating in a study of an investigational anti-cancer agent.

2. Has a diagnosis of immunodeficiency or any other form of immunosuppressive therapy.

3. Has not recovered from adverse events due to prior therapies, i.e. monoclonal antibody, chemotherapy, targeted small molecule therapy, radiation therapy, or surgery. - Note: Subjects with ≤ Grade 2 neuropathy, alopecia and general disorders and administration site conditions (per CTCAE version 4.0) are an exception to this criterion and may qualify for the study.

4. Has a known malignancy (other than breast cancer) except basal cell carcinoma or squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.

5. 5. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators, inhaled steroid or local steroid injections to the skin would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjögren's syndrome will not be excluded from the study.

6. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.

7. Has an active infection requiring systemic therapy.

8. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

9. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).

10. Has a known history of Human Immunodeficiency Virus (HIV).

11. Has a known active Hepatitis B or Hepatitis C

12. Have received a live vaccine within 30 days prior to the first dose of trial treatment.

13. Gastrointestinal tract disease or defect or previous history of colitis

14. Distant metastasis that involves occurrence of breast cancer outside of locoregional breast and lymph nodes area

15. Subjects requiring daily corticosteroids either via po or infusion

16. Myocardial infarction within 6 months before starting therapy, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or unstable cardiac arrhythmia requiring medication.