Clinical Trials /

Palbociclib and Endocrine Therapy for LObular Breast Cancer Preoperative Study (PELOPS)

NCT02764541

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Palbociclib</span> and <span class="go-doc-concept go-doc-intervention">Endocrine Therapy</span> for LObular Breast Cancer Preoperative Study (PELOPS)

Title

  • Brief Title: Palbociclib and Endocrine Therapy for LObular Breast Cancer Preoperative Study (PELOPS)
  • Official Title: Palbociclib and Endocrine Therapy for LObular Breast Cancer Preoperative Study (PELOPS): A Randomized Phase II Study of Palbociclib With Letrozole Versus Letrozole Alone for Invasive Lobular Carcinoma and Invasive Ductal Carcinoma
  • Clinical Trial IDs

    NCT ID: NCT02764541

    ORG ID: 16-052

    Trial Conditions

    Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Letrozole Femara Arm B Letrozole Followed By Endocrine Therapy, Letrozole Followed By Endocrine Therapy and Palbociclib
    Tamoxifen Soltanox Arm A Tamoxifen followed by Endocrine Therapy, Tamoxifen Followed By Endocrine Therapy and Palbociclib
    Palbociclib Ibrance Tamoxifen Followed By Endocrine Therapy and Palbociclib, Letrozole Followed By Endocrine Therapy and Palbociclib
    Endocrine Therapy Nolvadex Arm A Tamoxifen followed by Endocrine Therapy, Arm B Letrozole Followed By Endocrine Therapy, Tamoxifen Followed By Endocrine Therapy and Palbociclib, Letrozole Followed By Endocrine Therapy and Palbociclib

    Trial Purpose

    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.

    Detailed Description

    This is an open label phase II neoadjuvant clinical trial of Palbociclib in combination with
    endocrine therapy for hormone receptor positive early-stage breast cancer. The planned
    sample size is 180 participants. The study includes a "window treatment" phase followed by a
    treatment phase. In the window phase, participants will be treated with a two-week course of
    tamoxifen (Arm A) or letrozole (Arm B). In the treatment phase participants will be
    randomized to receive endocrine therapy in combination with palbociclib (Arm C) or endocrine
    therapy alone (Arm D) for a total duration of 24 weeks. Premenopausal patients with either
    invasive lobular or ductal carcinoma will be eligible to enroll directly into the treatment
    phase of the study. The study has two co-primary objectives: 1) To evaluate the difference
    in anti-proliferative activity of letrozole versus tamoxifen measured by changes in Ki67
    from baseline to research biopsy (day 15) within cohorts of hormone receptor positive breast
    cancer for patients with invasive lobular and ductal carcinoma. 2) To evaluate the
    pathologic complete response (pCR) of endocrine therapy plus palbociclib and of endocrine
    therapy alone in breast cancer patients diagnosed with hormone receptor positive invasive
    breast cancer.

    Trial Arms

    Name Type Description Interventions
    Arm A Tamoxifen followed by Endocrine Therapy Experimental Tamoxifen is given in the Window of Treatment phase for 2 weeks followed by Endocrine Therapy for 24 weeks. Tamoxifen, Endocrine Therapy
    Arm B Letrozole Followed By Endocrine Therapy Experimental Letrozole is given in the Window of Treatment phase for 2 weeks followed by Endocrine Therapy for 24 weeks. Letrozole, Endocrine Therapy
    Tamoxifen Followed By Endocrine Therapy and Palbociclib Experimental Tamoxifen is given in the Window of Treatment phase for 2 weeks followed by Endocrine Therapy in combination with Palbociclib for 24 weeks. Tamoxifen, Palbociclib, Endocrine Therapy
    Letrozole Followed By Endocrine Therapy and Palbociclib Experimental Letrozole is given in the Window of Treatment phase for 2 weeks followed by Endocrine Therapy in combination with Palbociclib for 24 weeks. Letrozole, Palbociclib, Endocrine Therapy

    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 all
    pathology-evaluated tumors meet the criteria outlined above

    - Bilateral breast cancers are allowed if all pathology-evaluated tumors meet the
    criteria outlined above

    - 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.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    To evaluate the difference in anti-proliferative activity of letrozole versus tamoxifen from baseline to research biopsy within cohorts of hormone receptor positive breast cancer for patients with invasive lobular and ductal carcinoma.

    To evaluate the pathologic response of endocrine therapy plus palbociclib and of endocrine therapy alone in breast cancer patients diagnosed with hormone receptor positive invasive breast cancer

    Secondary Outcome Measures

    Overrall Response Rate

    Progressive Free Survival

    Overall Survival

    Trial Keywords

    Breast Cancer

    Invasive Lobular Carcinoma