Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Aromatase Inhibitor and Durvalumab in Postmenopausal Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03874325
Recruitment Status : Recruiting
First Posted : March 14, 2019
Last Update Posted : March 14, 2019
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Tracking Information
First Submitted Date  ICMJE March 12, 2019
First Posted Date  ICMJE March 14, 2019
Last Update Posted Date March 14, 2019
Actual Study Start Date  ICMJE March 11, 2019
Estimated Primary Completion Date March 11, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 13, 2019)
Rate of Modified Preoperative Endocrine Prognostic Index (mPEPI) score of 0 [ Time Frame: 6 months ]
mPEPI score of 0 indicates a tumor size of 5 cm or less, negative lymph nodes, and Ki67 (proliferation index) or less than or equal to 2.7%. Drug combination will be determined to be efficacious if 7 or more participants achieve an mPEPI of 0.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: March 13, 2019)
  • Clinical Complete Response (CR) [ Time Frame: 6 months ]
    Clinical Complete response: Palpable lesion(s) identified at baseline are no longer palpable and there are no new lesion(s) or other signs of disease progression.
  • Clinical Partial Response (PR) [ Time Frame: 6 months ]
    Clinical Partial response: A reduction in the product of the two largest perpendicular diameters of the primary tumor by 50% or more.
  • Clinical Progression of Disease (PD) [ Time Frame: 6 months ]
    Clinical Progression of Disease (PD): An increase in the product of the two largest perpendicular diameters of the primary tumor by 25% or more or the presence of a new lesion.
  • Clinical Stable Disease (SD) [ Time Frame: 6 months ]
    Clinical Stable Disease (SD): Neither sufficient shrinkage to qualify for Clinical Partial Response (PR) nor sufficient increase to qualify for Clinical Progression of Disease (PD).
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 Aromatase Inhibitor and Durvalumab in Postmenopausal Breast Cancer
Official Title  ICMJE A Phase II Trial With Safety Run-in of Neoadjuvant Therapy With an Aromatase Inhibitor in Combination With Durvalumab (MEDI4736) in Postmenopausal Patients With Hormone-Receptor-Positive Breast Cancer
Brief Summary This study is to find out if an investigational drug called Durvalumab (MEDI4736) given together with a standard of care aromatase inhibitor drug can help people with breast cancer.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Breast Cancer
  • Hormone Receptor Positive Tumor
Intervention  ICMJE
  • Drug: Durvalumab
    1500 mg Durvalumab will be administered intravenously every 4 weeks for 6 months.
    Other Name: MEDI4736
  • Drug: Anastrozole 1mg
    Participants will self administer 1 mg anastrozole by mouth daily for 6 months.
    Other Name: Arimidex
  • Drug: Letrozole 2.5mg
    Participants intolerant to anastrozole will self administer 2.5 mg letrozole by mouth daily for 6 months. Exemestane may be substituted.
    Other Name: Femara
  • Drug: Exemestane 25 MG
    Participants intolerant to anastrozole will self administer 25 mg exemestane by mouth daily for 6 months. Letrozole may be substituted.
    Other Name: Aromasin
Study Arms  ICMJE
  • Experimental: Safety Run In: Durvalumab + Aromatase Inhibitor
    Participants will be administered 1500 mg Durvalumab intravenously every 4 weeks for 6 cycles. Participants will also take standard of care 1 mg anastrozole daily by mouth for 6 months. Letrozole 2.5 mg or exemastane 25 mg may be substituted for anastrozole if an intolerance to anastrozole is exhibited. Six participants will be enrolled in the safety run in stage. If 1 or fewer of six participants have a DLT, expansion stage will open to enrollment.
    Interventions:
    • Drug: Durvalumab
    • Drug: Anastrozole 1mg
    • Drug: Letrozole 2.5mg
    • Drug: Exemestane 25 MG
  • Experimental: Expansion: Durvalumab + Aromatase Inhibitor
    Participants will be administered 1500 mg Durvalumab intravenously every 4 weeks for 6 cycles. Participants will also take standard of care 1 mg anastrozole daily by mouth for 6 months. Letrozole 2.5 mg or exemastane 25 mg may be substituted for anastrozole if an intolerance to anastrozole is exhibited.
    Interventions:
    • Drug: Durvalumab
    • Drug: Anastrozole 1mg
    • Drug: Letrozole 2.5mg
    • Drug: Exemestane 25 MG
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: March 13, 2019)
46
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 11, 2025
Estimated Primary Completion Date March 11, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Postmenopausal, defined as meeting criteria per protocol.
  • Clinical T2-T4c, any N, MO by American Joint Committee on Cancer staging, 8th edition, with the goal being definitive surgery after completion of neoadjuvant therapy. Tumor is palpable and its size can be measured bidimensionally by tape, ruler or caliper technique. Largest tumor diameter over 2.0 cm.
  • Pathologic confirmation of invasive breast cancer that is estrogen receptor (ER) positive as defined in the protocol.
  • Invasive breast cancer is Human Epidermal Growth Factor Receptor 2 (HER2) negative as defined in the protocol protocol.
  • Documentation of mammogram and ultrasound [including ductal carcinoma in situ (DCIS) and invasive cancer] of the diseased breast performed within 60 days prior to enrollment. Mammograms for the unaffected contralateral breast is required within 12 months prior to enrollment.
  • Adequate organ and marrow function, as defined in the protocol.
  • Participants must be willing to undergo a research biopsy at baseline and after one cycle of treatment and to provide tissue obtained at surgery for biomarker and correlative studies.
  • Participants must be willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
  • If taking herbal or natural remedies that may have immune modulatory effects, participants must be willing to discontinue use prior to first dose of durvalumab.
  • Body weight over 30 kg.

Exclusion Criteria:

  • Participation in another clinical study with an investigational product during the last 4 weeks.
  • Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow up period of an interventional study.
  • Inflammatory breast cancer defined as clinically significant erythema of the breast and/or documented dermal lymphatic invasion (not direct skin invasion by tumor or peau d'orange without erythema).
  • An excisional biopsy of this breast cancer. Hormone replacement therapy of any type, megestrol acetate, or raloxifene within one week prior to registration.
  • Surgical axillary staging procedure prior to study entry. Note: Fine needle aspiration (FNA) or core needle biopsy of axillary node is permitted.
  • Treatment for this cancer including surgery, radiation therapy, chemotherapy, biotherapy, hormonal therapy or investigational agent prior to study entry.
  • Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
  • History of another primary malignancy except for malignancy treated with curative intent and with no known active disease ≥ 5 years or adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease or adequately treated carcinoma in situ without evidence of disease e.g., cervical cancer in situ.
  • History of ipsilateral invasive breast cancer regardless of treatment or ipsilateral ductal carcinoma in situ (DCIS) treated with radiotherapy or endocrine therapy or contralateral invasive breast cancer at any time.
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab, with the exceptions of intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra-articular injection); systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid; or steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). Some exceptions apply.
  • History of primary immunodeficiency.
  • History of allogeneic organ transplant.
  • Known allergy or history of hypersensitivity to durvalumab, or any excipient.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses, , or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
  • Known active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved hepatitis B infection are eligible. Patients positive for hepatitis C antibody are eligible only if polymerase chain reaction is negative for hepatitis C RNA. Note: This is applied only to patients with known infection. Screening tests for TB, hepatitis B and C, or HIV are not required.
  • Receipt of live attenuated vaccination within 30 days prior to receiving durvalumab. Note: Patients, if enrolled, should not receive live vaccine while receiving durvalumab and up to 30 days after the last dose of durvalumab.
  • Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.
  • Participants with uncontrolled seizures.
  • Participants with multi-centric breast cancer (defined as more than one lesion is invasive breast cancer in the same breast separated by ≥ 2 cm of normal breast tissue).
  • Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of investigational product.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Gender Eligibility Description: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03874325
Other Study ID Numbers  ICMJE MCC-19803
ESR-17-13182 ( Other Identifier: AstraZeneca )
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
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party H. Lee Moffitt Cancer Center and Research Institute
Study Sponsor  ICMJE H. Lee Moffitt Cancer Center and Research Institute
Collaborators  ICMJE AstraZeneca
Investigators  ICMJE
Principal Investigator: Hung Khong, MD H. Lee Moffitt Cancer Center and Research Institute
PRS Account H. Lee Moffitt Cancer Center and Research Institute
Verification Date March 2019

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