ER-positive, HER2-negative breast cancer MedDRA version: 20.0 Level: PT Classification code 10070577 Term: Oestrogen receptor positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Ibrance 125mg
Product Name: Ibrance 125mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Palbociclib
CAS Number: 571190-30-2
Concentration unit: mg milligram(s)
Concentration type
Sponsors
The University of Liverpool
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • 18 years of age or older • Histologically confirmed invasive breast cancer • ER positive (Allred =3) • HER2 negative per the 2013 ASCO/CAP guidelines • Axillary node negative or positive • Tumour measuring =15mm in longest diameter as measured clinically or radiologically* or any size tumour with axillary node involvement • Candidate for neoadjuvant endocrine therapy or chemotherapy • Pre- or postmenopausal women Postmenopausal status will be defined by the presence of any one of the following criteria: ?=55 years of age with an intact uterus and amenorrhoea =12 months at the time of diagnosis ?18 years with prior hysterectomy with intact ovaries and with a documented or current FSH and oestradiol level within the postmenopausal range (as per local institutional/laboratory standard) ?>18 years with prior bilateral oophorectomy • Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 • Adequate bone marrow function defined by Hb=10 g/dl, ANC >1.5 x109, PLT=100 x109/L. • Adequate renal function defined by a serum creatinine =1.5 x ULN. Adequate liver function defined by total bilirubin = 1.5 ULN (patients with Gilbert’s syndrome exempted), either ALT or AST =1.5 ULN and ALP =1.5 ULN • No contraindications to receiving palbociclib • Written informed consent, able to comply with treatment and follow-up. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 118 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: • Inflammatory breast cancer • Evidence of metastatic disease prior to 21-gene recurrence score assay testing • Any history of invasive malignancy within 5 years of starting study treatment (other than adequately treated basal cell carcinoma or squamous cell carcinoma of the skin and cervical carcinoma in situ) • Surgical axillary staging procedure prior to study procedure (with the exception of FNA or core biopsy) • Evidence of bleeding diathesis • Prior endocrine therapy or chemotherapy for breast cancer • Concomitant use (defined as use within 4 weeks prior to entry) of HRT or any other oestrogen-containing medication or supplement (including vaginal oestrogens and phytoestrogens) • Uncontrolled abnormalities of serum potassium, sodium, calcium or magnesium levels • Use of CYP3A inhibitors or inducers • Evidence of uncontrolled active infection • Evidence of significant medical condition or laboratory findings which, in the opinion of the investigator, makes it undesirable for the patient to participate in the trial • Pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to compare the changes in Ki67 proliferation index after 24 weeks treatment with oestrogen suppression therapy with or without palbociclib for patients with an intermediate RS score.;Secondary Objective: Secondary objectives for the randomised group: 1. To compare the objective radiological response rate as measured by ultrasound after 24 weeks treatment with oestrogen suppression therapy with or without palbociclib. 2. To compare the objective clinical response rate after 24 weeks treatment with oestrogen suppression therapy with or without palbociclib. 3. To compare the proportion of patients who undergo breast conservation after 24 weeks of treatment with oestrogen suppression therapy with or without palbociclib. 4. To compare the proportion of patients with improved surgical outcome after 24 weeks of treatment with oestrogen suppression therapy with or without palbociclib. 5. To compare the pathological complete response (pCR) rate after 24 weeks treatment with oestrogen suppression therapy with or without palbociclib. 6. To compare the proportion of tumours with a Preoperative Endocrine Prognostic Index (PEPI) score of 0 or 1 after 24 weeks of treatment with oestrogen suppressio;Primary end point(s): For the RCT the primary outcome is the change in level of proliferation marker Ki67 from baseline to 24 weeks. Note that for the observational cohort all outcomes are secondary, although the change in level of proliferation marker Ki67 will be assessed.;Timepoint(s) of evaluation of this end point: Baseline tissue sample taken from diagnostic biopsy (up to 28 days prior to study registration/randomisation) and a further tissue sample taken the end of treatment at 24 weeks. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints for the RCT interventional cohort i.e. the intermediate recurrence score group treated with oestrogen suppression therapy or oestrogen suppression plus palbociclib are as follows: • Objective of radiological response as measured by ultrasound after 24 weeks of treatment according to the ECOG criteria. • Objective clinical response after 24 weeks of treatment according to the ECOG criteria. • Breast conservation after 24 weeks of treatment. • Improved surgical outcome after 24 weeks of treatment. • Pathological complete response (pCR) after 24 weeks of treatment. • Preoperative Endocrine Prognostic Index (PEPI) score after 24 weeks. • Adjuvant chemotherapy after surgery. • Safety and tolerability in terms of: o grade 3+ toxicity classified by NCI-CTCAE v 4.0. o serious adverse events o withdrawal from trial treatment due to toxicity o experience of delay to scheduled surgery due to treatment related toxicities Secondary endpoints for the observational cohort i.e. low recurrence score group treated with oestrogen suppression therapy and high recurrence score group treated with chemotherapy: • Objective of radiological response as measured by ultrasound after 24 weeks of treatment according to the ECOG criteria. • Objective clinical response after 24 weeks of treatment according to the ECOG criteria. • Breast conservation after 24 weeks of treatment. • Improved surgical outcome after 24 weeks of treatment. • Pathological complete response (pCR) after 24 weeks of treatment. • Preoperative Endocrine Prognostic Index (PEPI) score after 24 weeks. • Adjuvant chemotherapy after surgery. • Level of Ki67 proliferation marker at baseline and at 24 weeks. ;Timepoint(s) of evaluation of this end point: Baseline and end of treatment at 24 weeks/surgery | — |
Countries
United Kingdom
Contacts
Public ContactEdiri O'Brien
Liverpool Clinical Trials Unit
Outcome results
None listed