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
Overview
- Phase
- Phase 2
- Intervention
- Tamoxifen
- Conditions
- Breast Cancer
- Sponsor
- Dana-Farber Cancer Institute
- Enrollment
- 195
- Locations
- 11
- Primary Endpoint
- Difference in Anti-proliferative Activity of Patients Given Letrozole Versus Tamoxifen During the Window Phase
- Status
- Active, not recruiting
- Last Updated
- 12 months ago
Overview
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.
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.
Investigators
Otto Metzger, MD
Otto Metzger, MD
Dana-Farber Cancer Institute
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
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.
Arms & Interventions
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.
Intervention: Tamoxifen
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.
Intervention: Endocrine Therapy
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.
Intervention: Letrozole
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.
Intervention: Endocrine Therapy
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.
Intervention: Tamoxifen
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.
Intervention: Palbociclib
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.
Intervention: Endocrine Therapy
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.
Intervention: Letrozole
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.
Intervention: Palbociclib
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.
Intervention: Endocrine Therapy
Outcomes
Primary Outcomes
Difference in Anti-proliferative Activity of Patients Given Letrozole Versus Tamoxifen During the Window Phase
Time Frame: baseline to day 15
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
Pathologic Complete Response (pCR) of Patients Given Endocrine Therapy Plus Palbociclib and of Endocrine Therapy Alone During the Treatment Phase
Time Frame: day 15 to 24 weeks
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.
Secondary Outcomes
- 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)
- Percentage of Participants With Clinical Response in Arm C and Arm D in 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)