POP: Randomized Phase II Study to Assess PD 0332991 in Breast Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| No Intervention: Control
|
|
| Experimental: 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. |
Drug: PD0332991
|
Outcome Measures
Primary Outcome Measures
- Anti proliferative response [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 Outcome Measures
- Dose Limiting Toxicity [Assessed at Day 8 and 15 after randomization]
Using NCI CTCAE 4.0
- Ki67 [Assessed at Day15 after randomization]
Relative change from baseline to surgery in Ki67 IHC expression ("relative" antripoliferative responders)
Eligibility Criteria
Criteria
Inclusion Criteria:
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Signed written informed consent
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Female patients aged 18 years or older.
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Histologically or cytologically confirmed untreated invasive carcinoma of the breast irrespective of HER2 and ER status
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No personal history of breast cancer within the last 5 years
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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.
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High proliferative tumor as defined by either Grade 3 or Ki67 ≥20% 8. No evidence of metastatic disease. 9. Eastern Cooperative Oncology Group (ECOG) performance status 0/1.
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Left ventricular ejection fraction (LVEF) of at least 50% 11. 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).
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For women of childbearing potential who are sexually active, agreement to use a highly effective, non-hormonal form of contraception or two effective forms of non-hormonal contraception during and for at least 6 months post-treatment.
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Patients must be affiliated to a social security system
Exclusion Criteria:
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Patients non-candidate for upfront breast surgery or candidate for neoadjuvant chemotherapy or hormonotherapy.
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Patients with previously treated breast cancer during the last 5 years or receiving another concomitant anticancer treatment like chemotherapy, immunotherapy, endocrine
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Known hypersensibility to PD0332991 or any of its components. 5. Difficulty to swallow oral medication 6. Serious uncontrolled concomitant disease that would put the patient at high risk for treatment-related complications.
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Patient whose general clinical condition does not consider postponing surgery 8.
Inadequate organ function, evidenced by the following laboratory results:
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Absolute neutrophil count <1,500 cells/mm3
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Platelet count <100,000 cells/mm3
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Hemoglobin <9 g/dL
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Total bilirubin greater than 1,5 times the upper limit of normal (ULN) (unless the patient has documented Gilbert's syndrome)
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Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) >2.5 x ULN
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Serum creatinine >2.0 mg/dL and/or 177 μmol/L clearance creatinine <50mL/min (calculated by Cockcroft-Gault method)
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International normalized ratio (INR) and activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) >1.5 x ULN (unless on therapeutic coagulation) 9. Uncontrolled hypertension (systolic >150 mmHg and/or diastolic > 100 mmHg) or clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident/stroke or myocardial infarction within 6 months prior to first study medication; unstable angina; CHF of New York Heart Association (NYHA) Grade II or higher; or serious cardiac arrhythmia requiring medication.
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Patients with a history of long-QT syndrome or documented family history of long-QT syndrome.
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QTc >470 12. serum potassium level < LLN 13. Uncontrolled intercurrent illness including but not limited to, known active infection with human immunodeficiency virus (HIV), hepatitis B or C virus or psychiatric illness/social situations that would limit compliance with study requirements.
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Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.
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Pregnant or breastfeeding patients
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Gustave Roussy | Villejuif | Val de Marne | France | 94805 |
Sponsors and Collaborators
- Gustave Roussy, Cancer Campus, Grand Paris
Investigators
- Principal Investigator: Monica Arnedos, MD, Gustave Roussy, Cancer Campus, Grand Paris
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 2013-002967-24
- 2013/2016