Clinical Trials /

Neoadjuvant Study of Abemaciclib, Durvalumab, and an Aromatase Inhibitor Early Stage Breast Cancer

NCT04088032

Description:

The purpose of this study is to test the efficacy, safety and tolerability of a combination of immunotherapy and anticancer drugs presurgery in patients with hormone-receptor positive breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Neoadjuvant Study of Abemaciclib, Durvalumab, and an Aromatase Inhibitor Early Stage Breast Cancer
  • Official Title: A Pilot Neoadjuvant Clinical Trial of Combination Therapy With Abemaciclib, Durvalumab (MEDI4736), and an Aromatase Inhibitor in Locally Advanced Hormone Receptor Positive Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 2019-00174 Neoadj Breast Pilot
  • NCT ID: NCT04088032

Conditions

  • Breast Cancer Female
  • Locally Advanced Breast Cancer
  • Hormone Receptor Positive Malignant Neoplasm of Breast

Interventions

DrugSynonymsArms
Abemaciclib, durvalumab and aromatase inhibitorActive

Purpose

The purpose of this study is to test the efficacy, safety and tolerability of a combination of immunotherapy and anticancer drugs presurgery in patients with hormone-receptor positive breast cancer.

Detailed Description

      The primary hypothesis is that a Programmed death-ligand 1 (PD-L1) immune checkpoint
      inhibitor combined with a Cyclin-dependent kinase 4/6 (CDK4/6) inhibitor will be well
      tolerated in early stage, hormone receptor positive (HR+) breast cancer patients treated with
      neoadjuvant endocrine therapy (NET). The secondary hypothesis and biomarker based endpoint is
      that patients with HR positive locally advanced breast cancer with low to intermediate
      stromal tumor-infiltrating lymphocytes (TILs) will demonstrate an increase in stromal TILs
      following NET when combined with abemaciclib and durvalumab for 4 cycles (16 weeks).
    

Trial Arms

NameTypeDescriptionInterventions
ActiveExperimentalExperimental treatment
  • Abemaciclib, durvalumab and aromatase inhibitor

Eligibility Criteria

        Inclusion Criteria:

          1. A signed, written informed consent will be obtained from the subject prior to
             performing any protocol-related procedures, including screening evaluations.

          2. Postmenopausal women age ≥ 18 years at time of study entry. Women will be considered
             post-menopausal if they have been amenorrheic for 12 months without an alternative
             medical cause. The following age-specific requirements apply:

               -  Women <50 years of age would be considered post-menopausal if they have been
                  amenorrheic for 12 months or more following cessation of exogenous hormonal
                  treatments and if they have luteinizing hormone and follicle-stimulating hormone
                  levels in the post-menopausal range for the institution or underwent surgical
                  sterilization (bilateral oophorectomy or hysterectomy).

               -  Women <50 years of age receiving luteinising hormone-releasing hormone (LHRH)
                  agonist for ovarian suppression are also eligible for the study but must initiate
                  LHRH agonist therapy at least 2 weeks prior to starting on study intervention.

               -  Women ≥ 50 years of age would be considered post-menopausal if they have been
                  amenorrheic for 12 months or more following cessation of all exogenous hormonal
                  treatments, had radiation-induced menopause with last menses >1 year ago, had
                  chemotherapy-induced menopause with last menses >1 year ago, or underwent
                  surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or
                  hysterectomy).

          3. Histologically confirmed estrogen and/or progesterone positive invasive breast cancer,
             defined as either estrogen and/or progesterone receptor (ER/PR) staining >10%, AND
             Human Epidermal Growth Factor Receptor 2 (HER2) negative by either
             Immunohistochemistry (IHC) or Fluorescent in situ Hybridization (FISH).

          4. Clinical stage II-III disease with no clinical or radiologic evidence of metastatic
             disease. Patients must have a measurable primary breast lesion as per Response
             Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines.

          5. Eastern Cooperative Oncology Group (ECOG) status < 1.

          6. Patient must be able to swallow pills.

          7. Adequate organ and marrow function as defined below and in Table 1:

               -  Hemoglobin ≥ 9 g/deciliter

               -  Absolute neutrophil count ≥ 1,500/mm3

               -  Platelet count ≥ 100,000/mm3

               -  Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2 ×
                  institutional upper limit of normal (ULN)

               -  Bilirubin ≤ 1.5 × ULN; for subjects with documented/suspected Gilbert's disease,
                  bilirubin ≤ 2 × ULN

               -  Creatinine clearance ≥ 50 mL/min as determined by the Cockcroft-Gault equation,
                  or creatinine ≤1.5 x ULN

          8. Patient is 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.

          9. Must have a life expectancy of at least 12 weeks.

        Exclusion Criteria:

          1. Any serious preexisting medical condition(s) that would place the patient at increased
             risk for toxicities including interstitial lung disease, severe dyspnea at rest or
             requiring oxygen therapy, history of major surgical resection involving the stomach or
             small bowel.

          2. Body weight < 30 kg (or 66.5 lbs.). If during the study, the patient's weight drops to
             < 30 Kg (or 66.5 lbs), they will be withdrawn from the study.

          3. Females who are pregnant or lactating.

          4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
             angina pectoris, cardiac arrhythmia, severe active peptic ulcer disease or gastritis,
             or psychiatric illness/social situations that would limit compliance with study
             requirement or compromise the ability of the subject to give written informed consent

          5. Active or prior documented autoimmune disease within the past 2 years. NOTE: Subjects
             with vitiligo, Grave's disease, Hashimoto's disease, or psoriasis not requiring
             systemic treatment (within the past 2 years) are eligible

          6. History of significant cardiac disease including heart failure, ventricular
             arrhythmia, or prolonged QT syndrome.

          7. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease,
             ulcerative colitis, or a preexisting chronic condition resulting in baseline ≥ Grade 2
             diarrhea.)

          8. History of primary immunodeficiency, or subjects who are known to be HIV (Human
             Immunodeficiency Virus ) positive

          9. History of organ transplant that requires use of immunosuppressives

         10. Known allergy or reaction to any of the study drugs.

         11. Other invasive malignancy within 2 years except for noninvasive malignancies such as
             cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma
             in situ of the breast that has/have been surgically cured

         12. Major surgical procedure (as defined by the investigator) within 30 days prior to the
             first dose of study drugs or still recovering from prior surgery

         13. Known history of tuberculosis

         14. Subjects who are known to be hepatitis B or C positive

         15. History of prior therapy with a checkpoint (PD-L1/PD-1) including durvalumab or CDK4/6
             inhibitor

         16. History of prior ipsilateral radiation therapy to the cancer-affected breast

         17. History of prior therapy with an investigational anticancer therapy within 6 weeks
             prior to the first dose of study drugs

         18. Prior chemotherapy or aromatase inhibitor therapy for breast cancer

         19. Current or prior use of immunosuppressive medication within 28 days before the first
             dose of durvalumab, with the exceptions of intranasal, topical, and inhaled
             corticosteroids or systemic corticosteroids at physiologic doses not to exceed 10
             mg/day of prednisone or equivalent

         20. Patients who must take strong cytochrome cytochrome P450 (CYP3A) inhibitors such as
             clarithromycin, diltiazem, verapamil, itraconazole, or ketoconazole

         21. Receipt of live attenuated vaccination within 30 days prior to study entry or within
             30 days of receiving durvalumab

         22. Concurrent enrollment in another therapeutic clinical study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time Frame:Through study completion, up to 24 weeks
Safety Issue:
Description:The primary endpoints will be safety and tolerability of the study intervention

Secondary Outcome Measures

Measure:Pathologic response at surgery
Time Frame:At the time of definitive surgery
Safety Issue:
Description:Pathologic response at surgery by Preoperative Endocrine Prognostic Index (PEPI) score
Measure:Pathologic response at surgery
Time Frame:At the time of definitive surgery
Safety Issue:
Description:Pathologic response at surgery by change in Ki-67% from pre and surgical biopsies

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Alison Stopeck

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