Clinical Trials /

Aromatase Inhibitor and Durvalumab in Postmenopausal Breast Cancer

NCT03874325

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Ductal Carcinoma In Situ
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Aromatase Inhibitor and Durvalumab in Postmenopausal Breast Cancer
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: MCC-19803
  • SECONDARY ID: ESR-17-13182
  • NCT ID: NCT03874325

Conditions

  • Breast Cancer
  • Hormone Receptor Positive Tumor

Interventions

DrugSynonymsArms
DurvalumabMEDI4736Safety Run In: Durvalumab + Aromatase Inhibitor
Anastrozole 1mgArimidexSafety Run In: Durvalumab + Aromatase Inhibitor
Letrozole 2.5mgFemaraSafety Run In: Durvalumab + Aromatase Inhibitor
Exemestane 25 MGAromasinSafety Run In: Durvalumab + Aromatase Inhibitor

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Safety Run In: Durvalumab + Aromatase InhibitorExperimentalParticipants 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.
  • Durvalumab
  • Anastrozole 1mg
  • Letrozole 2.5mg
  • Exemestane 25 MG
Expansion: Durvalumab + Aromatase InhibitorExperimentalParticipants 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.
  • Durvalumab
  • Anastrozole 1mg
  • Letrozole 2.5mg
  • Exemestane 25 MG

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of Modified Preoperative Endocrine Prognostic Index (mPEPI) score of 0
Time Frame:6 months
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Clinical Complete Response (CR)
Time Frame:6 months
Safety Issue:
Description: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.
Measure:Clinical Partial Response (PR)
Time Frame:6 months
Safety Issue:
Description:Clinical Partial response: A reduction in the product of the two largest perpendicular diameters of the primary tumor by 50% or more.
Measure:Clinical Progression of Disease (PD)
Time Frame:6 months
Safety Issue:
Description: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.
Measure:Clinical Stable Disease (SD)
Time Frame:6 months
Safety Issue:
Description: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).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Trial Keywords

  • HR+

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