Clinical Trials /

Biological and Clinical Effects of Palbociclib With Ovarian Suppression and Letrozole in the Neoadjuvant Treatment of Breast Cancer

NCT03628066

Description:

This study will look at the safety and effectiveness of the combination of palbociclib and letrozole and ovarian suppression for premenopausal patients who have ER-positive/HER2-negative breast cancer that has not yet been treated.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Biological and Clinical Effects of Palbociclib With Ovarian Suppression and Letrozole in the Neoadjuvant Treatment of Breast Cancer
  • Official Title: An Assessment of the Biological and Clinical Effects of Palbociclib (PD 0332991) With Ovarian Suppression and Letrozole in the Neoadjuvant Treatment of Patients With Premenopausal Estrogen-Receptor Positive/HER2-Negative Primary Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: NSABP FB-13
  • NCT ID: NCT03628066

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
LetrozoleFemaraArm 1
PalbociclibIbranceArm 1
GoserelinZoladexArm 1

Purpose

This study will look at the safety and effectiveness of the combination of palbociclib and letrozole and ovarian suppression for premenopausal patients who have ER-positive/HER2-negative breast cancer that has not yet been treated.

Detailed Description

      NSABP FB-13 is a phase II, open label study to examine the biological and clinical effect of
      neoadjuvant endocrine therapy with letrozole, palbociclib and ovarian suppression in
      premenopausal patients with estrogen-receptor (ER) positive, HER2-negative, early invasive
      breast cancer.

      Premenopausal women newly diagnosed with ER-positive/HER2-negative early breast cancer who
      are suitable candidates for neoadjuvant endocrine therapy will be invited to join the FB-13
      trial. A screening Oncotype DX Breast Recurrence Score® will be performed by Genomic Health,
      Inc. (GHI) on the diagnostic tissue of consenting patients to verify eligibility.

      Patients will be stratified into one of two approximately equal sized cohorts based on
      baseline Breast Recurrence Score (RS) (cohort 1: patients with RS less than 11 or cohort 2:
      patients with RS 11 to less than 26).

      Patients in both cohorts will receive letrozole 2.5 mg by mouth daily, palbociclib 125 mg by
      mouth daily for 21 days of a 28 day cycle, and goserelin 3.6 mg subcutaneous injection on Day
      1 of each 28 day cycle. At Week 6 of study therapy, patients will have two core-cut biopsies.
      Patients from both cohorts who have a Ki67 less than 10% level will continue receiving study
      therapy for a total of 6 cycles. Patients with a persistent Ki67 greater than or equal to 10%
      at week 6 will permanently discontinue study therapy and begin neoadjuvant chemotherapy or
      proceed to surgery at the discretion of the treating physician.

      Pre-treatment samples and post-surgical samples will be collected and analysed to identify
      subgroups of patients who may derive the most clinical benefit. The results of the biological
      analyses may allow a target sensitive population to be selected for future trials. The tissue
      collected in FB-13 will form an integral part of the primary analyses; so all core biopsies
      in this trial will be mandated for patients.

      Two core-cut biopsies will be collected from each patient at baseline, after 6 weeks of study
      therapy, and upon completion of study therapy (24 weeks) at the time of definitive surgery.

      Blood samples will be collected at baseline, 4 weeks, and at 24 weeks for estrone and
      estradiol levels to demonstrate ovarian suppression. A 4-week estradiol level in the
      postmenopausal range will be required to receive further treatment on study.
    

Trial Arms

NameTypeDescriptionInterventions
Arm 1ExperimentalOncotype DX Breast recurrence score on diagnostic tissue Daily Letrozole for 24 weeks + Palbociclib daily for 24 weeks + Goserelin weekly for 24 weeks
  • Letrozole
  • Palbociclib
  • Goserelin

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must be premenopausal. Patients with a hysterectomy: menopausal status must
             be confirmed by estradiol and FSH.

          -  Operable hormonal receptor (HR) positive (ER/PR greater than or equal to 10%), HER2-
             negative, invasive early breast cancer, suitable for neoadjuvant AI treatment and
             ovarian suppression; HR- positive and HER2-negative as determined by American Society
             of Clinical Oncology/College of American Pathologists (ASCO-CAP ) guidelines.

          -  Diagnostic breast tissue must have an Oncotype DX Breast Recurrence Score® of less
             than 26 as determined by Genomic Health, Inc.

          -  No known severe hypersensitivity reactions to compounds similar to palbociclib or
             palbociclib excipients or to endocrine treatments.

          -  A breast tumor with an ultrasound size of at least 2.0 cm.

          -  Patients must have the ability to swallow oral medication.

          -  ECOG performance status of 0 or 1.

          -  At the time of randomization, blood counts performed within 2 weeks prior to
             randomization must meet the following criteria:

               -  ANC must be greater than or equal to 1500/mm3

               -  Platelet count must be greater than or equal to 100,000/mm3

               -  Hemoglobin must be greater than or equal to 10g/dL.

          -  INR must be within normal limits of the local laboratory ranges. For laboratories that
             do not report an ULN for the INR assay, use less than or equal to 1.2 as the value for
             the ULN.

          -  The following criteria for evidence of adequate hepatic function performed within 2
             weeks prior to study entry must be met:

               -  Total bilirubin must be less than or equal to ULN for the lab unless the patient
                  has a bilirubin elevation greater than ULN to 1.5 x ULN due to Gilbert's disease
                  or similar syndrome involving slow conjugation of bilirubin; and

               -  Alkaline phosphatase must be must be less than or equal to 1.5 x ULN for the lab;
                  and

               -  AST and ALT must be less than or equal to 1.5 x ULN for the lab.

          -  Serum creatinine performed within 2 weeks prior to study entry must be less than or
             equal to 1.25 x ULN or estimated creatinine clearance greater than or equal to 60
             mL/min (as calculated using the method standard for the institutions).

        Exclusion Criteria:

          -  Active hepatitis B or hepatitis C with abnormal liver function tests.

          -  HIV positive patients receiving antivirals.

          -  Inflammatory/inoperable breast cancer.

          -  HER2-positive as determined using ASCO-CAP Guidelines.

          -  Oncotype Dx Breast Recurrence Score® result on diagnostic breast tissue greater than
             or equal to 26.

          -  Prior endocrine therapy for breast cancer.

          -  Any invasive malignancy within previous 5 years (other than basal cell carcinoma or
             cervical carcinoma in situ).

          -  Other nonmalignant systemic disease that would preclude the patient from receiving
             study treatment or would prevent required follow up such as:

               -  Active infection or chronic infection requiring chronic suppressive antibiotics;

               -  Malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, resection
                  of the stomach or small bowel, or other disease or condition significantly
                  affecting gastrointestinal function;

               -  Chronic daily treatment with corticosteroids with a dose of greater than or equal
                  to 10 mg/day methylprednisolone equivalent (excluding inhaled steroids);

               -  Seizure disorders requiring medication.

          -  Diagnosis by fine needle aspiration (FNA) alone or excisional biopsy or lumpectomy
             performed prior to study entry.

          -  Surgical axillary staging procedure prior to study procedure (with exception of FNA or
             core biopsy).

          -  Definitive clinical or radiologic evidence of metastatic disease.

          -  History of ipsilateral invasive breast cancer regardless of treatment or ipsilateral
             DCIS treated with radiotherapy or contralateral invasive breast cancer at any time.

          -  Any treatment, including radiotherapy, chemotherapy, and/or targeted therapy,
             administered for the currently diagnosed breast cancer prior to study entry.

          -  Use of any medication or substances that are strong inhibitors or inducers of CYP3A
             isoenzymes. Class III or Class IV myocardial disease as described by the New York
             Heart Association; a recent history (within 6 months) of myocardial infarction, or
             symptomatic arrhythmia at the time of randomization.

               -  Class III: Patients with cardiac disease resulting in marked limitation of
                  physical activity. Such patients are comfortable at rest. Less than ordinary
                  physical activity that causes fatigue, palpitation, dyspnea, or anginal pain.

               -  Class IV: Patients with cardiac disease resulting in inability to perform any
                  physical activity without discomfort. Symptoms of cardiac insufficiency or
                  anginal syndrome may be present even at rest.

          -  The investigator should assess the patient to determine if she has any psychiatric or
             addictive disorder or other condition that, in the opinion of the investigator, would
             preclude her from meeting the study requirements.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete Cell cycle arrest
Time Frame:From study entry to the time of the 6 week tumor biopsy to assess Ki67, approximately 6 weeks
Safety Issue:
Description:Percentage of patients with a Ki67 less than 2.7%

Secondary Outcome Measures

Measure:Objective response rate
Time Frame:From study entry to the 24 week clinical assessment/ultrasound, approximately 24 weeks
Safety Issue:
Description:Objective response rate determined by breast tumor assessment measured by clinical exam and ultrasound
Measure:Pathologic complete response to study therapy (breast)
Time Frame:From study entry to time of surgery, generally 3 to 4 weeks after completion of study therapy at approximately 28 weeks
Safety Issue:
Description:Percentage of patients with absence of invasive cancer in surgical specimens
Measure:Pathologic complete response to study therapy (breast with nodes)
Time Frame:From study entry to time of surgery, generally 3 to 4 weeks after completion of study therapy at approximately 28 weeks
Safety Issue:
Description:Percentage of patients with absence of invasive cancer in surgical specimens
Measure:Correlation between Oncotype DX Breast Recurrence Score® and clinical Complete Response (cCR)
Time Frame:From study entry to the 24 week clinical assessment/ultrasound, approximately 24 weeks
Safety Issue:
Description:Correlation of the Oncotype DX Breast Recurrence Score® with clinical Complete Response
Measure:Correlation between Oncotype DX Breast Recurrence Score® and pathologic Complete Response (pCR)
Time Frame:From study entry to time of surgery, generally 3 to 4 weeks after completion of study therapy at approximately 28 weeks
Safety Issue:
Description:Correlation of the Oncotype DX Breast Recurrence Score® with pathologic Complete Response
Measure:Correlation between Oncotype DX Breast Recurrence Score® and Complete Cell cycle arrest rate (CCAR)
Time Frame:From the time of study entry to time of the 6-week tumor biopsy to assess Ki67, approximately 6 weeks
Safety Issue:
Description:Correlation of the Oncotype DX Breast Recurrence Score® with Complete Cell cycle arrest rate
Measure:Comparison between surgical intent and surgery received
Time Frame:From study entry to time of surgery, generally 3 to 4 weeks after completion of study therapy at approximately 28 weeks
Safety Issue:
Description:Changes between surgical intent declared at study start and actual surgery received after treatment
Measure:Comparison of estrone levels
Time Frame:From study entry to the 4 week blood draw, approximately 4 weeks
Safety Issue:
Description:Compare the estrone level at baseline to that after neoadjuvant treatment
Measure:Comparison of estradiol levels
Time Frame:From study entry to the 4 week blood draw, approximately 4 weeks
Safety Issue:
Description:Compare the estradiol level after neoadjuvant treatment

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:NSABP Foundation Inc

Trial Keywords

  • Ovarian Suppression
  • Neoadjuvant
  • Premenopausal
  • Estrogen-Receptor Positive
  • HER2-Negative
  • Primary
  • Palbociclib
  • Letrozole
  • Goserelin
  • Ki67
  • Oncotype DX Breast Recurrence Score
  • Open-Label

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