Clinical Trials /

Neoadjuvant Tamoxifen, Palbociclib, Avelumab in Estrogen Receptor Positive Breast Cancer

NCT03573648

Description:

Eligible patients with estrogen receptor positive breast cancer will undergo a biopsy and be randomized to receive tamoxifen (T) versus tamoxifen with palbociclib (PT) in a 1:1 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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Neoadjuvant Tamoxifen, Palbociclib, Avelumab in Estrogen Receptor Positive Breast Cancer
  • Official Title: A Pilot Study of IMMUNe mOdulation in Early Stage Estrogen Receptor Positive Breast Cancer Treated With neoADjuvant Avelumab, Palbociclib, and Tamoxifen: The ImmunoADAPT Study

Clinical Trial IDs

  • ORG STUDY ID: J1836
  • SECONDARY ID: IRB00164275
  • NCT ID: NCT03573648

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
AvelumabBavencioTamoxifen
TamoxifenNolvadexTamoxifen
PalbociclibIbranceTamoxifen with Palbociclib

Purpose

Eligible patients with estrogen receptor positive breast cancer will undergo a biopsy and be randomized to receive tamoxifen (T) versus tamoxifen with palbociclib (PT) in a 1:1 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 tamoxifen (20mg PO daily) +/- palbociclib (125mg PO 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 tamoxifen +/- palbociclib (thus 4 cycles total,
      including run-in without avelumab). 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.
    

Trial Arms

NameTypeDescriptionInterventions
TamoxifenActive ComparatorEligible patients with ER-positive breast cancer will undergo a biopsy and be randomized to receive tamoxifen (T) versus tamoxifen with palbociclib (PT) in a 1:1 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.
  • Avelumab
  • Tamoxifen
Tamoxifen with PalbociclibActive ComparatorEligible patients with ER-positive breast cancer will undergo a biopsy and be randomized to receive tamoxifen (T) versus tamoxifen with palbociclib (PT) in a 1:1 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.
  • Avelumab
  • Tamoxifen
  • Palbociclib

Eligibility Criteria

        Inclusion Criteria:

          -  Stage II-III ER-positive breast cancer.

          -  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 benefit from endocrine therapy (i.e. 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.

          -  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 tamoxifen, 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, 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

        - Female patients who are pregnant or nursing are not eligible.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Clinical Complete Response
Time Frame:2 years
Safety Issue:
Description:The number of patients with a response to treatment as assessed by MRI breast imaging

Secondary Outcome Measures

Measure:Safety and Tolerability as determined by number of patients who experience Adverse Events
Time Frame:2 years
Safety Issue:
Description:Adverse events will be assessed by CTCAE at each treatment visit and 30 days after completion of therapy.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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