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

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ClinicalTrials.gov Identifier: NCT02764541
Recruitment Status : Recruiting
First Posted : May 6, 2016
Last Update Posted : November 9, 2018
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Otto Metzger, Dana-Farber Cancer Institute

Brief 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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Letrozole Drug: Tamoxifen Drug: Palbociclib Drug: Endocrine Therapy Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 24, 2016
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : November 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Arm A Tamoxifen followed by Endocrine Therapy
Tamoxifen is given in the Window of Treatment phase for 2 weeks followed by Endocrine Therapy for 24 weeks.
Drug: Tamoxifen
Other Name: Soltanox

Drug: Endocrine Therapy
Other Name: Nolvadex

Experimental: Arm B Letrozole Followed By Endocrine Therapy
Letrozole is given in the Window of Treatment phase for 2 weeks followed by Endocrine Therapy for 24 weeks.
Drug: Letrozole
Other Name: Femara

Drug: Endocrine Therapy
Other Name: Nolvadex

Experimental: Tamoxifen Followed By Endocrine Therapy and Palbociclib
Tamoxifen is given in the Window of Treatment phase for 2 weeks followed by Endocrine Therapy in combination with Palbociclib for 24 weeks.
Drug: Tamoxifen
Other Name: Soltanox

Drug: Palbociclib
Other Name: Ibrance

Drug: Endocrine Therapy
Other Name: Nolvadex

Experimental: Letrozole Followed By Endocrine Therapy and Palbociclib
Letrozole is given in the Window of Treatment phase for 2 weeks followed by Endocrine Therapy in combination with Palbociclib for 24 weeks.
Drug: Letrozole
Other Name: Femara

Drug: Palbociclib
Other Name: Ibrance

Drug: Endocrine Therapy
Other Name: Nolvadex




Primary Outcome Measures :
  1. Window Phase:To evaluate the difference in anti-proliferative activity of letrozole versus tamoxifen within cohorts of hormone receptor positive breast cancer for patients with invasive lobular and ductal carcinoma. [ Time Frame: 2 years ]
    Anti-proliferative activity will be calculated by the fold-change in percent of Ki67 from baseline and Day 15 research biopsy samples.

  2. Treatment Phase: 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 [ Time Frame: 2 Years ]
    Pathologic response will be reported as the Residual Cancer Burden (RCB). RCB will be calculated using the MD Anderson Residual Cancer Burden calculator.


Secondary Outcome Measures :
  1. Overrall Response Rate [ Time Frame: 2 years ]
  2. Progressive Free Survival [ Time Frame: 2 years ]
  3. Overall Survival [ Time Frame: 2 years ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02764541


Contacts
Contact: Otto Metzger, MD 617-632-3352 ometzger@partners.org

Locations
United States, Connecticut
Stamford Hospital Recruiting
Stamford, Connecticut, United States, 06904
Contact: K.M. Steve Lo, MD       slo@stamhealth.org   
United States, Maine
Eastern Maine Medical Center Recruiting
Brewer, Maine, United States, 04412
Contact: Thomas H. Openshaw, MD       topenshaw@emhs.org   
United States, Massachusetts
Dana-Farber at St. Elizabeth's Medical Center Recruiting
Boston, Massachusetts, United States, 02135
Contact: Caroline Block, MD       caroline_block@dfci.harvard.edu   
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Steven Come, MD    617-667-4599    scome@bidmc.harvard.edu   
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Otto F Metzger, MD    617-632-3800    ometzger@partners.org   
Principal Investigator: Otto F Metzger, MD         
DF/BWCC at Milford Regional Medical Center Recruiting
Milford, Massachusetts, United States, 01757
Contact: Michael Constantine, MD       michael_constantine@dfci.harvard.edu   
DF/BWCC in clinical affiliation with South Shore Hospital Recruiting
South Weymouth, Massachusetts, United States, 02190
Contact: Meredith Faggen, MD       meredith_faggen@dfci.harvard.edu   
United States, Rhode Island
Lifespan Recruiting
Providence, Rhode Island, United States, 02903
Contact: Mary Anne Fenton, MD       mfenton@lifespan.org   
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Denise A. Yardley, MD       dyardley@tnonc.com   
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Ingrid Mayer, MD       ingrid.mayer@vanderbilt.edu   
Sponsors and Collaborators
Dana-Farber Cancer Institute
Pfizer
Investigators
Principal Investigator: Otto Metzger, MD Dana-Farber Cancer Institute

Responsible Party: Otto Metzger, Otto Metzger, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT02764541     History of Changes
Other Study ID Numbers: 16-052
First Posted: May 6, 2016    Key Record Dates
Last Update Posted: November 9, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Otto Metzger, Dana-Farber Cancer Institute:
Breast Cancer
Invasive Lobular Carcinoma

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Palbociclib
Tamoxifen
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents
Protein Kinase Inhibitors