Neoadjuvant Endocrine Therapy, Palbociclib, Avelumab in Estrogen Receptor Positive Breast Cancer

NCT03573648 | Active Not Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: J1836IRB00164275WI231034
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 4

Brief Summary

Eligible patients with estrogen receptor positive breast cancer will undergo a biopsy and be randomized to receive endocrine therapy (ET) versus endocrine therapy with palbociclib (PET) in a 1:2 ratio. After 1 cycle (28 days) another biopsy will be obtained, and both arms will receive avelumab (A) for 3 additional cycles. Patients will then undergo breast surgery.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Clinical Complete Response

  The number of patients with a response to treatment as assessed by MRI breast imaging

  2 years

Secondary Outcomes (1)

• Safety and Tolerability as determined by number of patients who experience Adverse Events

  2 years

Study Arms (2)

Endocrine Therapy

ACTIVE COMPARATOR

Eligible patients with ER-positive breast cancer will undergo a biopsy and be randomized to receive endocrine therapy (ET) versus endocrine therapy with palbociclib (PET) in a 1:2 ratio. A 1:2 ratio means that twice as many participants will be assigned to the PET arm as compared to the ET arm. After 1 cycle (28 days) another biopsy will be obtained, and both arms will receive avelumab (A) for 3 additional cycles. Patients will then undergo breast surgery.

Drug: Avelumab; Drug: Endocrine therapy

Endocrine Therapy with Palbociclib

ACTIVE COMPARATOR

Eligible patients with ER-positive breast cancer will undergo a biopsy and be randomized to receive endocrine therapy (ET) versus endocrine therapy with palbociclib (PET) in a 1:2 ratio. A 1:2 ratio means that twice as many participants will be assigned to the PET arm as compared to the ET arm. After 1 cycle (28 days) another biopsy will be obtained, and both arms will receive avelumab (A) for 3 additional cycles. Patients will then undergo breast surgery.

Drug: Avelumab; Drug: Endocrine therapy; Drug: Palbociclib

Interventions

Palbociclib DRUG

Palbociclib (125 mg) will be given orally on days 1-21 of each cycle x 4 cycles.

Also known as: Ibrance

Endocrine Therapy with Palbociclib

Avelumab DRUG

Avelumab (10 mg/kg) will be given intravenously on cycles 2 - 4, every 2 weeks.

Also known as: Bavencio

Endocrine Therapy; Endocrine Therapy with Palbociclib

Endocrine therapy DRUG

The endocrine therapy given will depend on menopausal status. Premenopausal women will receive tamoxifen AND either Goserelin or Leuprolide: * Tamoxifen (20mg) will be given orally daily x 4 cycles. (Other Names: Nolvadex) * Goserelin (3.6mg) will be given subcutaneously (under the skin) on Day 1 of each cycle x 4 cycles. (Other Names: Zoladex) * Leuprolide (3.75mg) will be given intramuscularly (in the buttock, thigh, or upper arm) on Day 1 of each cycle x 4 cycles. (Other Names: Leuprorelin, Lupron, Eligard) Postmenopausal women will receive letrozole: \- Letrozole (2.5mg) will be given orally daily each cycle x 4 cycles. (Other Names: Femara)

Also known as: Hormone therapy

Endocrine Therapy; Endocrine Therapy with Palbociclib

Eligibility Criteria

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

You may qualify if:

• Stage II-III ER-positive breast cancer
• Tumor evaluable either by ultrasound or by touch.
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group performance status of 1 or less.
• Adequate organ and bone marrow function within 28 days prior to registration.
• Females of child-bearing potential and males must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 30 days following completion of therapy.
• Females of child-bearing potential must have a negative pregnancy test within 7 days prior to registration on study.
• Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study

You may not qualify if:

• Evidence of metastatic disease or inflammatory breast cancer.
• Patients not felt to be sensitive to endocrine therapy, such that a neoadjuvant endocrine-based approach would not be appropriate (i.e. PR-negative, high grade/Ki67, high gene expression profile, clinically aggressive presentation)
• Previous treatment with endocrine therapy within the last 10 years (i.e. tamoxifen, aromatase inhibitors).
• Previous treatment with CDK4/6 inhibitors, or immune checkpoint inhibitors.
• Use of SSRIs and/or any concomitant use of medications outlined in section 6.5 within 4 days prior to enrollment. If patients are on stable doses and there are no good alternatives, the treating physician may discuss with Study Chair.
• May not be receiving any other investigational agents.
• May not be receiving immunosuppressive therapy within 2 weeks of study entry.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to corresponding endocrine therapy (tamoxifen, aromatase inhibitors, GnRH agonists), palbociclib, and avelumab are not eligible.
• May not have had a prior diagnosis of cancer if it has been \< 3 years since their last treatment (with the exception of squamous cell carcinoma or basal cell carcinoma of the skin or cervical intraepithelial neoplasia). NOTE: Patients with a history of breast cancer or breast cancer treatment within the last 10 years are also excluded. Any previous radiation to affected breast is excluded.
• Autoimmune disease within the last 3 years with the exception of: Vitiligo or alopecia; Hypothyroidism on stable doses of thyroid medication; and Psoriasis not requiring systemic therapy
• Uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible: Ongoing or active infection requiring systemic treatment (including HIV, TB, hepatitis viruses), symptomatic congestive heart failure, cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina pectoris, cardiac arrhythmia, psychiatric illness/social situations that would limit compliance with study requirements, any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints
• Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
• Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines
• Prior organ transplantation including allogenic stem-cell transplantation
• Female patients who are pregnant or nursing are not eligible.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Pfizer: collaborator
• Allegheny Health Network: collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (4)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Allegheny Health Network

Pittsburgh, Pennsylvania, 15224, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

avelumab; palbociclib

Condition Hierarchy (Ancestors)

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

Study Officials

• Cesar A. Santa-Maria, MD, MSCI

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: June 20, 2018
• First Posted: June 29, 2018
• Study Start: November 13, 2018
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)