Palbociclib and Endocrine Therapy for LObular Breast Cancer Preoperative Study (PELOPS)
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Letrozole; Tamoxifen; Palbociclib; Endocrine Therapy
Intervention MeSH terms: Tamoxifen; Letrozole; Palbociclib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 195.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Breast Cancer; Invasive Lobular Carcinoma

Summary:

      This research study is evaluating how well Breast Cancer responds to preoperative treatment
      with Endocrine treatment in combination with a drug called Palbociclib or Endocrine treatment
      alone as possible treatments for Hormone Receptor Positive Breast Cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have Stage I to III histologically confirmed invasive carcinoma of the
             breast. A minimum tumor size of at least 1.5 cm determined by physical exam or imaging
             (whichever is larger) is required.

          -  Patients must have histologically confirmed hormone receptor positive (ER and/or PR),
             HER2 negative, invasive breast cancer. ER, PR and HER2 measurements should be
             performed according to institutional guidelines, in a CLIA-approved setting in the US
             or certified laboratories for Non-US regions. Cut-off values for positive/negative
             staining should be in accordance with current ASCO/CAP (American Society of Clinical
             Oncology/College of American Pathologists) guidelines. Central confirmation is not
             required for ER, PR, or HER statuses.

          -  Patients with equivocal HER2 in situ hybridization results according to current
             ASCO/CAP guidelines are allowed, as long as the clinician has determined that they
             should be treated as HER2 negative.

          -  For the window phase: Patients must have histologically confirmed invasive lobular
             carcinoma or invasive ductal carcinoma. No central confirmation of histological
             subtype is necessary for enrollment.

          -  For the treatment phase: Patients with any histological subtype are eligible.

          -  Women 18 years of age. Men are not eligible.

          -  ECOG performance status 0 or 1

          -  Required laboratory values:

               -  Absolute neutrophil count ≥ 1,500/mm3

               -  Platelets ≥ 100,000/mm3

               -  Hemoglobin ≥ 10g/dL

               -  Total serum bilirubin ≤ ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin
                  within normal range in patients with documented Gilbert's Syndrome

               -  Aspartate amino transferase (AST or SGOT) and alanine amino transferase (ALT or
                  SGPT) ≤ 2.0 × institutional ULN

               -  Serum creatinine within normal institutional limits or creatinine clearance ≥ 60
                  mL/min/1.73 m2 for patients with serum creatinine levels above institutional ULN

          -  Postmenopausal patients defined as no spontaneous menses ≥1 year (12 months) or post
             bilateral surgical oophorectomy. Premenopausal patients are eligible to participate
             provided they are considered in chemical menopause. Premenopausal patients should
             receive ongoing treatment with LHRH agonists (goserolin or leuprolide). Premenopausal
             patients must be enrolled directly into the treatment phase of the study.

          -  Patient must agree to the required research biopsies at baseline and after the
             two-week treatment with endocrine therapy in the initial part of the study ("window
             phase"); or at baseline and after two-week treated with endocrine therapy plus or
             minus palbociclib for those patients enrolled directly into the treatment phase of the
             study.

          -  Patients must be able and willing to swallow and retain oral medication without a
             condition that would interfere with enteric absorption.

          -  Breast imaging should include imaging of the ipsilateral axilla. For subjects with a
             clinically negative axilla, a sentinel lymph node biopsy will be performed either
             before or after preoperative therapy at the discretion of the subject's physicians.
             For subjects with a clinically positive axilla, a needle aspiration, core biopsy or
             SLN procedure will be performed to determine the presence of metastatic disease in the
             lymph nodes.

          -  Patients with multifocal or multicentric disease are eligible if the treating
             clinician has determined the patient should be treated as ER+ and HER2- negative.

          -  Bilateral breast cancers are allowed if the treating clinician has determined the
             patient should be treated as ER+ and HER2- negative.

          -  Serum or urine pregnancy test must be negative in women judged premenopausal within 7
             days of randomization, or in women with amenorrhea of less than 12 months at time of
             randomization. Pregnancy testing does not need to be pursued in patients who are
             judged as postmenopausal before randomization, as determined by local practice, or who
             have undergone bilateral oophorectomy, total hysterectomy, or bilateral tubal
             ligation.

          -  Premenopausal patients must agree to use adequate contraception for the duration of
             protocol treatment and for 6 months after the last treatment with palbociclib.
             Adequate contraception is defined as one highly effective form (i.e. abstinence, male
             or female sterilization) OR two effective forms (e.g. non-hormonal IUD and
             condom/occlusive cap with spermicidal foam / gel / film / cream/ suppository).
             Hormonal contraceptive methods are not allowed.

          -  Patients with a history of ipsilateral or contralateral DCIS are eligible.

          -  Patients may concurrently receive bisphosphonates or rank ligand inhibitors while on
             this study if necessary for treatment or prevention of osteopenia or osteoporosis.
             Prior treatment with LHRH agonists is allowed for premenopausal women. Topical vaginal
             estrogen therapy is allowable.

          -  Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  Concurrent therapy with other Investigational Products.

          -  Prior therapy with any CDK inhibitor.

          -  Patients with Stage IV breast cancer are not eligible. Baseline staging to document
             absence of metastatic disease is not required, however is recommended as determined by
             institutional practice (in patients where there may be a reasonable suspicion of
             advanced disease e.g., large tumors, clinically positive axillary lymph nodes, signs
             and symptoms). If performed, reports of these examinations must be available.
             Examination type for staging, i.e. X-ray, sonography, bone scans, CT, MRI, and/or
             PET-CT, is at the discretion of the investigator.

          -  History of allergic reactions attributed to compounds of chemical or biologic
             composition similar to palbociclib.

          -  Patients receiving any medications or substances that are potent inhibitors or
             inducers of CYP3A isoenzymes within 7 days of randomization

          -  Uncontrolled illness including, but not limited to, ongoing or active infection,
             symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia,
             diabetes, or psychiatric illness/social situations that would limit compliance with
             study requirements. Ability to comply with study requirements is to be assessed by
             each investigator at the time of screening for study participation.

          -  Pregnant women, or women of childbearing potential without a negative pregnancy test
             (serum or urine) within 7 days prior to randomization, irrespective of the method of
             contraception used, are excluded from this study because the effect of palbociclib on
             a developing fetus is unknown. Breastfeeding must be discontinued prior to study
             entry.

          -  Patients with a history of any malignancy are ineligible except for the following
             circumstances:

               -  Patients with a malignancy history other than invasive breast cancer are eligible
                  if they have no active malignancy and are deemed by the investigator to be at low
                  risk for recurrence of that malignancy.

               -  Patients with the following cancers are eligible: ductal carcinoma in situ of the
                  breast, cervical cancer in situ, and non-metastatic non-melanomatous skin
                  cancers.

          -  Patients on combination antiretroviral therapy, i.e. those who are HIV-positive, are
             ineligible because of the potential for pharmacokinetic interactions or increased
             immunosuppression with palbociclib. HIV testing is not required, but patients must not
             be known to be HIV-positive.

          -  Patients receiving concurrent exogenous hormone therapy (hormone replacement therapy,
             oral or any other hormonal contraceptives such as hormonal contraceptive coil are not
             eligible.

          -  Patients are not eligible if they have previously received endocrine therapy within 5
             years prior to diagnosis of the current malignancy. This includes use for prophylactic
             reasons, including treatment of osteoporosis or cancer prevention with tamoxifen,
             raloxifene, or AI.