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Trial record 1 of 1 for:    NCT03573648
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Neoadjuvant Endocrine Therapy, Palbociclib, Avelumab in Estrogen Receptor Positive Breast Cancer (ImmunoADAPT)

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ClinicalTrials.gov Identifier: NCT03573648
Recruitment Status : Recruiting
First Posted : June 29, 2018
Last Update Posted : February 24, 2021
Sponsor:
Collaborators:
Pfizer
Allegheny Health Network
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Tracking Information
First Submitted Date  ICMJE June 20, 2018
First Posted Date  ICMJE June 29, 2018
Last Update Posted Date February 24, 2021
Actual Study Start Date  ICMJE November 13, 2018
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 20, 2018)
Clinical Complete Response [ Time Frame: 2 years ]
The number of patients with a response to treatment as assessed by MRI breast imaging
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 20, 2018)
Safety and Tolerability as determined by number of patients who experience Adverse Events [ Time Frame: 2 years ]
Adverse events will be assessed by CTCAE at each treatment visit and 30 days after completion of therapy.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Neoadjuvant Endocrine Therapy, Palbociclib, Avelumab in Estrogen Receptor Positive Breast Cancer
Official Title  ICMJE A Pilot Study of IMMUNe mOdulation in Early Stage Estrogen Receptor Positive Breast Cancer Treated With neoADjuvant Avelumab, Palbociclib, and Endocrine Therapy: The ImmunoADAPT Study
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Drug: Avelumab
    Avelumab (10 mg/kg) will be given intravenously on cycles 2 - 4, every 2 weeks.
    Other Name: Bavencio
  • 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)

    Other Name: Hormone therapy
  • Drug: Palbociclib
    Palbociclib (125 mg) will be given orally on days 1-21 of each cycle x 4 cycles.
    Other Name: Ibrance
Study Arms  ICMJE
  • Active Comparator: 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.
    Interventions:
    • Drug: Avelumab
    • Drug: Endocrine therapy
  • Active Comparator: 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.
    Interventions:
    • Drug: Avelumab
    • Drug: Endocrine therapy
    • Drug: Palbociclib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 20, 2018)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Hopkins Breast Trials 410-614-1361 hopkinsbreasttrials@jhmi.edu
Contact: Sidney Kimmel Cancer Center Clinical Research Office 410-955-8866 jhcccro@jhmi.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03573648
Other Study ID Numbers  ICMJE J1836
IRB00164275 ( Other Identifier: JHM-IRB )
WI231034 ( Other Identifier: Pfizer Inc )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Sponsor  ICMJE Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators  ICMJE
  • Pfizer
  • Allegheny Health Network
  • National Institutes of Health (NIH)
Investigators  ICMJE
Study Chair: Cesar A. Santa-Maria, MD, MSCI Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
PRS Account Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP