A Phase II Randomized Study Evaluating the Biological and Clinical Effects of the Combination of Palbociclib With Letrozole as Neoadjuvant Therapy in Post-Menopausal Women With Estrogen-Receptor Positive Primary Breast Cancer

Official Title

A Phase II Randomized Study Evaluating the Biological and Clinical Effects of the Combination of Palbociclib With Letrozole as Neoadjuvant Therapy in Post-Menopausal Women With Estrogen-Receptor Positive Primary Breast Cancer

Summary:

This study will look at effects the combination of palbociclib and letrozole may have on estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer tumours which have not yet been treated. Letrozole is a type of endocrine therapy called an aromatase inhibitor (AI) and is standard treatment for post-menopausal women with ER-positive/HER2-negative breast cancer.

Trial Description

Primary Outcome:

• Measurement of the proliferation marker Ki67 (% positive tumour cells)
• Clinical Complete Response (cCR): Number of patients who have resolution of measurable lesions or no new lesions or other signs of disease progression compared to baseline.

Secondary Outcome:

• Pathological Complete Response (pCR): Number of patients with no lesions in breast and nodes at time of surgery
• Preoperative Endocrine Prognostic Index (PEPI) score:
• Number and severity of adverse events
• Molecular and genetic profiles of samples collected.
• Measurement of Ki67 marker

The FB-11 study is a Phase II, randomized, open label, four arm study to examine the biological and clinical effect of neoadjuvant letrozole with or without palbociclib in the first-line treatment of estrogen-receptor (ER) positive, HER2-negative early invasive breast cancer. The co-primary aims of this study are to to compare the changes in the proliferation marker Ki67, and to compare clinical response after 14 weeks of therapy with letrozole with or without palbociclib. The FB-11 study initiative is a joint partnership between the NSABP Foundation, Inc. (NSABP) Department of Site and Study Management (DSSM) and United Kingdom (UK) co-investigators at the Royal Marsden NHS Foundation Trust and the Institute of Cancer Research (ICR). Parallel protocols will be conducted in the US and Canada (FB-11), and the UK (PALLET) with joint analysis of interim and final data. Postmenopausal women, newly diagnosed with ER-positive/HER2-negative early breast cancer, who are suitable candidates for neoadjuvant endocrine therapy will be invited to join the FB-11/PALLET trial. Approximately 306 patients will be accrued to this study. Each collaborative group will recruit at least 1/3 and no more than 2/3 of the target accrual. Patients will be randomized to one of four treatment arms (3:2:2:2 ratio). Treatment in the first 14 weeks of neoadjuvant therapy will be:Arm A Letrozole alone; Arm B Letrozole for 2 weeks followed by letrozole + palbociclib to week 14; Arm C Palbociclib for 2 weeks followed by letrozole + palbociclib to week 14; Arm D Letrozole + palbociclib to week 14. Letrozole will be administered orally as a 2.5mg daily tablet. Palbociclib will be administered orally as 125mg capsules, daily on a schedule of 3 weeks (21 days) on, 1 week (7 days) off of a 4 week [28 day] cycle. The end of study therapy for patients in Arm A will be completion of week 14. Patients in Arms B, C, and D will complete study therapy following 14 days of palbociclib in the final treatment cycle past 14 weeks if treatment delays have occurred. Note: After week 14 (end of study therapy) all patients should continue letrozole until surgery. Letrozole is not considered study therapy beyond completion of week 14 for Arm A or after 14 days of palbociclib in the final treatment cycle for patients in Arms B, C, and D. Following completion of study therapy, surgery will be scheduled for 15-18 weeks post-randomization. Post-surgical treatment will be at discretion of treating clinician, following local protocols, and not influenced by allocation of treatment within the FB-11/PALLET study. Toxicity will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0).

View this trial on ClinicalTrials.gov