Clinical Trials /

Neo-Adjuvant Abemaciclib With Fulvestrant in Patients With ER/PR +HER Negative Breast Cancer

NCT04305236

Description:

This is a phase 2 single-arm, open-label determining efficacy of Neo-adjuvant Abemaciclib and Fulvestrant in subjects with Hormone receptor positive patients with localized non-metastatic breast cancer who develop local recurrence while on adjuvant endocrine therapy with molecular evidence of endocrine resistance.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase II Trial on Neo-Adjuvant Abemaciclib With Fulvestrant in Patients With ER/PR +HER Negative Breast Cancer
  • Official Title: A Phase II Open Label Trial of Neo-Adjuvant Abemaciclib With Fulvestrant in Patients Who Develop Localized Recurrence While on Adjuvant Endocrine Therapy With Molecular Evidence of Endocrine Resistance

Clinical Trial IDs

  • ORG STUDY ID: UCI 18-79
  • SECONDARY ID: 2020-5660
  • NCT ID: NCT04305236

Conditions

  • Breast Neoplasm
  • Hormone Receptor Positive Breast Carcinoma

Interventions

DrugSynonymsArms
AbemaciclibVERZENIO™Abemaciclib and Fulvestrant
FulvestrantFASLODEX®Abemaciclib and Fulvestrant

Purpose

This is a phase 2 single-arm, open-label determining efficacy of Neo-adjuvant Abemaciclib and Fulvestrant in subjects with Hormone receptor positive patients with localized non-metastatic breast cancer who develop local recurrence while on adjuvant endocrine therapy with molecular evidence of endocrine resistance.

Trial Arms

NameTypeDescriptionInterventions
Abemaciclib and FulvestrantExperimentalAbemaciclib will be administered orally at the dose of 150 mg twice daily. Fulvestrant will be administered intramuscularly at an initial loading dose of 500mg on days 1 and 15 of the first cycle and then 500 mg intramuscularly every first day of each subsequent cycle. One cycle is 28 days.
  • Abemaciclib
  • Fulvestrant

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have a diagnosis of HR+ breast cancer. To fulfill the requirement of HR+
             disease, a breast cancer must express, by immunohistochemistry (IHC), at least one of
             the hormone receptors (ER, progesterone receptor [PgR]) as defined in the relevant
             American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP)
             Guidelines (Hammond et al. 2010):

             1. For ER and PgR assays to be considered positive, ≥1% of tumor cell nuclei must be
             immunoreactive by immunohistochemistry (IHC) (Hammond et al. 2010).

          -  Patients must have Loco regional breast cancer (Stage I, Stage II and stage III per
             AJCC 8th edition criteria for staging of breast cancer)

          -  Patients must have localized recurrence while on adjuvant endocrine therapy

          -  Patients must have any known molecular evidence of endocrine resistance by next
             generation sequencing

          -  Age ≥ 18 years.

          -  ECOG performance status 0-1

          -  Have post-menopausal status as defined by following:

               1. Prior bilateral oophorectomy

               2. Age ≥ 60 years

               3. Age < 60 and amenorrheic (non-treatment-induced amenorrhea secondary to
                  tamoxifen, toremifene, ovarian suppression, or chemotherapy) for at least 12
                  months. Follicle-stimulating hormone (FSH) and estradiol must be in the
                  postmenopausal range.

          -  Have at least one measurable disease as defined per RECIST 1.1

          -  Adequate organ and marrow function as defined below:

               1. Hemoglobin* > 8 g/dL

               2. Absolute neutrophil count ≥ 1,500/mcL

               3. Total bilirubin ≤ 1.5 X institutional ULN, Patients with Gilbert's syndrome with
                  a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are
                  permitted

               4. AST (SGOT)/ALT (SPGT) ≤ 2.5 X institutional ULN

               5. Creatinine ≤ 1.5 X institutional ULN

                    1. *Patients may receive transfusion of packed red blood cells (PRBC) to
                       achieve this hemoglobin level at the discretion of the investigator;
                       however, initial study drug treatment must not begin earlier than the day
                       after the PRBC transfusion.

          -  Able to swallow oral medications

          -  Patients who received adjuvant radiotherapy must have completed and fully recovered
             from the acute effects of radiotherapy. A washout period of at least 14 days is
             required between end of radiotherapy and screening for the study.

          -  Patients who received chemotherapy must have recovered (Common Terminology Criteria
             for Adverse Events [CTCAE] Grade ≤1) from the acute effects of chemotherapy except for
             residual alopecia or Grade 2 peripheral neuropathy prior to enrollment. A washout
             period of at least 21 days is required between last chemotherapy dose and enrollment
             (provided the patient did not receive radiotherapy).

          -  Any known markers of response or resistance to CDK 4/6 inhibitors to be present in the
             biopsy specimen

          -  If patients have been treated with prior Neo-Adjuvant chemotherapy at the time of
             primary diagnosis and not at the time of recurrence, they will be included in the
             study.

          -  Must be able to sign a written informed consent, are reliable, willing to be available
             for the duration of the study and are willing to follow study procedures

        Exclusion Criteria:

          -  Stage IV metastatic breast cancer

             1. This study will utilize the American Joint Committee on Cancer (AJCC) staging
             system, eight edition that provides a strategy for grouping patients with respect to
             prognosis. The AJCC has designated staging by TNM classification. The researchers will
             also review tumor size, lymph node status, and estrogen-receptor and
             progesterone-receptor levels in the tumor tissue.

          -  Patients with HER2 positive and triple negative breast cancer

             1. To fulfill the requirement of HER2- and Triple negative disease, a breast cancer
             must not demonstrate, at initial diagnosis or upon subsequent biopsy, overexpression
             of HER2 or should not express ER or PR receptors by either IHC or in-situ
             hybridization (ISH) as defined in the relevant ASCO/CAP guidelines (Wolff et al.
             2013).

          -  Inflammatory breast cancer

          -  Newly diagnosed endocrine naïve patients

          -  No molecular evidence of endocrine resistance

          -  Prior treatment with any CDK 4/6 inhibitor and/or Fulvestrant

          -  Pre-menopausal women

          -  Are currently receiving an investigational drug in a clinical trial or participating
             in any other type of medical research judged not to be scientifically or medically
             compatible with this study. If a patient is currently enrolled in a clinical trial
             involving non-approved use of a device, then agreement with the principal investigator
             is required to establish eligibility

          -  Have had major surgery within 14 days prior to enrollment to allow for post-operative
             healing of the surgical wound

          -  Have initiated bisphosphonates or approved RANK ligand therapy for breast cancer with
             osseous metastasis, if patients are received Zolendronic acid or Denosumab in the
             adjuvant manner then such patients will be allowed participate

          -  Have serious preexisting medical conditions that, in the judgment of the investigator,
             would preclude participation in this study (for example, history of major surgical
             resection involving the stomach or small bowel or preexisting Crohn's disease or
             ulcerative colitis , interstitial lung disease, severe dyspnea at rest, any
             pre-existing chronic condition resulting in baseline grade 2 or higher diarrhea)

          -  Have a personal history within the last 12 months of any of the following conditions:
             syncope or cardiovascular etiology, ventricular tachycardia, ventricular fibrillation
             or sudden cardiac arrest

          -  Have a history of any other cancer (except for non-melanoma skin cancer or carcinoma
             in situ of the cervix) unless in complete remission with no therapy for a minimum of
             three years or have received an autologous or allogeneic stem-cell transplant

          -  Have an active bacterial or fungal infection or a detectable viral infection (for
             example HIV or viral hepatitis). Screening is not required for enrollment

          -  Recent therapy with a biologic agent or a monoclonal therapy is excluded. Wash out of
             at least three half-lives of monoclonal antibody would be required to be enrolled.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants with a pathological complete response
Time Frame:From start of study treatment to surgery, on average we expect 6 months.
Safety Issue:
Description:This is defined as the percentage of subjects who achieve a pathological complete response (pCR). A pCR is defined by no evidence of tumor cells in the final surgical specimen.

Secondary Outcome Measures

Measure:Overall Response Rate
Time Frame:From start of study treatment to surgery, on average we expect 6 months.
Safety Issue:
Description:To assess the overall response rate to the combination of Abemaciclib and Fulvestrant. Overall response rate (ORR) is defined as confirmed complete response (CR) and partial response (PR). Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1): Complete Response (CR) is defined as the disappearance of all target lesions; Partial Response (PR) is defined as a 30% decrease in the sum of diameters of target lesions. ORR = CR + PR
Measure:Percentage of Participants who undergo breast conserving surgery
Time Frame:From start of study treatment to surgery, on average we expect 6 months.
Safety Issue:
Description:This is defined as the percentage of subjects who undergo breast conserving surgery after receiving Abemaciclib and Fulvestrant
Measure:Recurrence Disease Free Survival
Time Frame:Up to 5 years
Safety Issue:
Description:Recurrence disease free survival will be defined as the time from surgery until patient develops recurrence.
Measure:Percentage of Grade 3-5 Adverse Events
Time Frame:From start of study treatment to surgery, on average we expect 6 months.
Safety Issue:
Description:To evaluate the safety and tolerability of administering Abemaciclib and Fulvestrant. Toxicity and adverse events are based on the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 5.0.
Measure:Percentage change in Ki 67
Time Frame:From start of study treatment to surgery, on average we expect 6 months.
Safety Issue:
Description:Percentage change in the Ki 67 will be evaluated from baseline to the treated specimen after breast surgery
Measure:Preoperative Endocrine Prognostic Index Score
Time Frame:From start of study treatment to surgery, on average we expect 6 months.
Safety Issue:
Description:The preoperative endocrine prognostic index (PEPI) Score is a score that is used in clinical trials to assess response to Neo-Adjuvant endocrine therapy. The PEPI score takes into account the tumor and nodal stage, level of ER expression and Ki 67 following neoadjuvant endocrine therapy.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of California, Irvine

Last Updated

March 9, 2020