Randomized Short-term Pre-surgical Study to Assess the Effects of PD 0332991 in Early Breast Cancer Patients
Overview
- Phase
- Phase 2
- Intervention
- PD0332991
- Conditions
- Untreated Operable Early Breast Cancer
- Sponsor
- Gustave Roussy, Cancer Campus, Grand Paris
- Enrollment
- 132
- Locations
- 1
- Primary Endpoint
- Anti proliferative response
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
This is a Phase II study trying to identify whether short term treatment with PD0332991 yields anti-proliferative response -defined by a low level of Ki67 expression (IHC) at surgery- or induces senescence as determined by SABG expression (IHC) in tumors from patients with early breast cancer non-candidates for neoadjuvant hormonotherapy or chemotherapy, as compared to no treatment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed written informed consent
- •Female patients aged 18 years or older.
- •Histologically or cytologically confirmed untreated invasive carcinoma of the breast irrespective of HER2 and ER status
- •No personal history of breast cancer within the last 5 years
- •Candidates for initial breast surgery, with a minimum size of 15 mm measured by breast US. Bilateral and multifocal tumors are allowed, assuming tumor evaluations and pre- and post-treatment biopsies are performed in the same target lesion.
- •High proliferative tumor as defined by either Grade 3 or Ki67 ≥20%
- •No evidence of metastatic disease.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0/
- •Left ventricular ejection fraction (LVEF) of at least 50%
- •Negative pregnancy test in women of childbearing potential within 14 days prior to treatment initiation (premenopausal or less than 12 months of amenorrhea post-menopause, and who have not undergone surgical sterilization).
Exclusion Criteria
- •Patients non-candidate for upfront breast surgery or candidate for neoadjuvant chemotherapy or hormonotherapy.
- •Patients with previously treated breast cancer during the last 5 years or receiving another concomitant anticancer treatment like chemotherapy, immunotherapy, endocrine
- •Known hypersensibility to PD0332991 or any of its components.
- •Difficulty to swallow oral medication
- •Serious uncontrolled concomitant disease that would put the patient at high risk for treatment-related complications.
- •Patient whose general clinical condition does not consider postponing surgery
- •Inadequate organ function, evidenced by the following laboratory results:
- •Absolute neutrophil count \<1,500 cells/mm3
- •Platelet count \<100,000 cells/mm3
- •Hemoglobin \<9 g/dL
Arms & Interventions
PD0332991
Patients will be randomized 3:1 to be treated with PD0332991 125mg/day orally for a total duration of 14 days (or 100 mg/day for a total duration of 21 days depending on results of interim analysis) with last treatment taken the day previous to the surgical procedure.
Intervention: PD0332991
Outcomes
Primary Outcomes
Anti proliferative response
Time Frame: Assessed at Day 15 after randomization
percentage of patients who at Day 15 have a natural logarithm of percentage positive IHC staining Ki67 of \<1 for each study drug (Ki67 "absolute" antiproliferative responders).
Secondary Outcomes
- Dose Limiting Toxicity(Assessed at Day 8 and 15 after randomization)
- Ki67(Assessed at Day15 after randomization)