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

NCT ID: NCT03573648

Last Updated: 2025-09-22

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-13
• Study Completion Date: 2026-06-30

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.

Detailed Description

Patients will be treated with endocrine therapy +/- palbociclib (125mg, taken orally, daily for 21 days, 7 days off ) for 1 cycle (1 cycle =28 days) and undergo a repeat biopsy, MRI, and blood draw at Cycle 2, Day 1. Afterwards avelumab will be added to both arms. Avelumab will be administered 10mg/kg IV every 14 days (1 cycle = 2 doses = 28 days). Patients will be treated for 3 cycles of avelumab with endocrine therapy +/- palbociclib (thus 4 cycles total, including run-in without avelumab).

The kind of endocrine therapy given will depend on menopausal status and will be a standard treatment. For premenopausal women, the endocrine therapy will be daily tamoxifen (20mg taken orally daily for 28 days), plus either Leuprolide (3.75mg taken intramuscularly) or Goserelin (3.6mg taken subcutaneously) on Day 1 of each cycle. For postmenopausal women, it will be daily letrozole (2.5mg taken orally).

Patients will be treated so long as there is no clinical evidence of progression and therapy is tolerated. Patients who experience progressive disease (25% increase) of their tumor will cease study treatment and undergo end-of-study assessment (including repeat MRI) and surgery. Otherwise, patients completing all 4 cycles of therapy will undergo MRI and surgery.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Endocrine Therapy

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.

Group Type: ACTIVE_COMPARATOR

Avelumab

Intervention Type: DRUG

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

Endocrine therapy

Intervention Type: 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)

Endocrine Therapy with Palbociclib

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.

Group Type: ACTIVE_COMPARATOR

Avelumab

Intervention Type: DRUG

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

Endocrine therapy

Intervention Type: 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)

Palbociclib

Intervention Type: DRUG

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

Interventions

Avelumab

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

Intervention Type: DRUG

Endocrine therapy

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)

Intervention Type: DRUG

Palbociclib

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

Intervention Type: DRUG

Other Intervention Names

Bavencio; Hormone therapy; Ibrance

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Allegheny Health Network

OTHER

Sponsor Role: collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cesar A. Santa-Maria, MD, MSCI

Role: STUDY_CHAIR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Sibley Memorial Hospital

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

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Allegheny Health Network

Pittsburgh, Pennsylvania, United States

Countries

United States

Other Identifiers

IRB00164275

Identifier Type: OTHER

Identifier Source: secondary_id

WI231034

Identifier Type: OTHER

Identifier Source: secondary_id

J1836

Identifier Type: -

Identifier Source: org_study_id