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

NCT02764541 | Active Not Recruiting Phase 2 Results DMC

• 1 other identifier: 16-052
• Study Type: interventional
• Target: 195
• Locations: 1 country
• Sites: 11

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.

Conditions

Breast Cancer

Keywords

Breast Cancer; Invasive Lobular Carcinoma

Outcome Measures

Primary Outcomes (2)

• Difference in Anti-proliferative Activity of Patients Given Letrozole Versus Tamoxifen During the Window Phase

  Log fold change in anti-proliferative activity of Letrozole versus Tamoxifen within cohorts of hormone receptor positive breast cancer for patients with invasive lobular and ductal carcinoma during the window phase. Higher absolute value indicates larger change in the anti-proliferative activity

  baseline to day 15

• Pathologic Complete Response (pCR) of Patients Given Endocrine Therapy Plus Palbociclib and of Endocrine Therapy Alone During the Treatment Phase

  Residual Cancer Burden index (RCB) between hormone receptor positive invasive breast cancer patients given endocrine therapy plus palbociclib (Arm C) and endocrine therapy alone (Arm D). RCB score is used to assess the response to neoadjuvant chemotherapy in breast cancer patients and is in a scale of 0 to infinity. Higher RCB score indicates more tumor burden remaining, thus worse outcome.

  day 15 to 24 weeks

Secondary Outcomes (4)

• Odds Ratio of Achieving Cell Cycle Arrest at the End of Window Phase

  baseline to day 15

• Change in RCB Index Between Arm C and Arm D During the Treatment Phase

  day 15 to 24 weeks

• Number of Participants With RCB Response in Arm C and Arm D During the Treatment Phase

  day 15 to 24 weeks

• Percentage of Participants With Clinical Response in Arm C and Arm D in the Treatment Phase

  day 15 to 24 weeks

Study Arms (4)

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.

Drug: Tamoxifen; Drug: 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.

Drug: Letrozole; Drug: 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.

Drug: Tamoxifen; Drug: Palbociclib; Drug: 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.

Drug: Letrozole; Drug: Palbociclib; Drug: Endocrine Therapy

Interventions

Letrozole DRUG

Also known as: Femara

Arm B Letrozole Followed By Endocrine Therapy; Letrozole Followed By Endocrine Therapy and Palbociclib

Tamoxifen DRUG

Also known as: Soltanox

Arm A Tamoxifen followed by Endocrine Therapy; Tamoxifen Followed By Endocrine Therapy and Palbociclib

Palbociclib DRUG

Also known as: Ibrance

Letrozole Followed By Endocrine Therapy and Palbociclib; Tamoxifen Followed By Endocrine Therapy and Palbociclib

Endocrine Therapy DRUG

Also known as: Nolvadex

Arm A Tamoxifen followed by Endocrine Therapy; Arm B Letrozole Followed By Endocrine Therapy; Letrozole Followed By Endocrine Therapy and Palbociclib; Tamoxifen Followed By Endocrine Therapy and Palbociclib

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Pfizer: collaborator

Study Sites (11)

Stamford Hospital

Stamford, Connecticut, 06904, United States

Location

Eastern Maine Medical Center

Brewer, Maine, 04412, United States

Location

Dana-Farber at St. Elizabeth's Medical Center

Boston, Massachusetts, 02135, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

DF/BWCC at Milford Regional Medical Center

Milford, Massachusetts, 01757, United States

Location

DF/BWCC in clinical affiliation with South Shore Hospital

South Weymouth, Massachusetts, 02190, United States

Location

Lifespan

Providence, Rhode Island, 02903, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (3)

• Weiss A, Jin Q, Tayob N, Wrabel E, DeMeo M, Carter J, Constantine M, Faggen M, Block C, Fenton MA, Lo KMS, Openshaw T, Yardley D, Kennedy L, Bedrosian I, Mittendorf EA, Jeselsohn R, Metzger Filho O, King TA. Axillary Management and Outcomes After Neoadjuvant Endocrine Therapy in the Randomized PELOPS Trial. Ann Surg Oncol. 2025 Nov 23. doi: 10.1245/s10434-025-18697-5. Online ahead of print.

  PMID: 41276768 DERIVED

• Weiss A, Revette A, Nava-Coulter B, Mittendorf EA, Filho OM, King TA. Surgeon Perspectives on Axillary Management Following Neoadjuvant Endocrine Therapy: Results from a Qualitative Substudy of the PELOPS Trial. Ann Surg Oncol. 2025 Nov 21. doi: 10.1245/s10434-025-18695-7. Online ahead of print.

  PMID: 41272386 DERIVED

• Hermida-Prado F, Xie Y, Sherman S, Nagy Z, Russo D, Akhshi T, Chu Z, Feit A, Campisi M, Chen M, Nardone A, Guarducci C, Lim K, Font-Tello A, Lee I, Garcia-Pedrero J, Canadas I, Agudo J, Huang Y, Sella T, Jin Q, Tayob N, Mittendorf EA, Tolaney SM, Qiu X, Long H, Symmans WF, Lin JR, Santagata S, Bedrosian I, Yardley DA, Mayer IA, Richardson ET, Oliveira G, Wu CJ, Schuster EF, Dowsett M, Welm AL, Barbie D, Metzger O, Jeselsohn R. Endocrine Therapy Synergizes with SMAC Mimetics to Potentiate Antigen Presentation and Tumor Regression in Hormone Receptor-Positive Breast Cancer. Cancer Res. 2023 Oct 2;83(19):3284-3304. doi: 10.1158/0008-5472.CAN-23-1711.

  PMID: 37450351 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Carcinoma, Lobular

Interventions

Letrozole; Tamoxifen; palbociclib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Ductal, Lobular, and Medullary

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Otto Metzger
• Organization: Dana-Farber Cancer Institute

otto_metzger@dfci.harvard.edu

6176323800

Study Officials

• Otto Metzger, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Otto Metzger, MD

Study Record Dates

• First Submitted: May 4, 2016
• First Posted: May 6, 2016
• Study Start: May 24, 2016
• Primary Completion: February 1, 2022
• Study Completion (Estimated): April 1, 2031
• Last Updated: May 7, 2025
• Results First Posted: August 31, 2023

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)