Breast Cancer
Conditions
Keywords
Advanced breast cancer, Postmenopausal, ER positive, Her2 negative
Brief summary
This study aims to assess the activity of PD0332991 in monotherapy and in combination with the endocrine therapy (anastrozole, letrozole, exemestane or fulvestrant) on which the patient has progressed in the previous line for advanced breast cancer in order to reverse endocrine resistance.
Detailed description
In a clinical context, there is a lack of molecular compounds with demonstrated clinical activity in delaying/reversing resistance to endocrine agents. CDK 4/6 inhibitors may represent a biologically-driven option in this context. With the present study investigators aim to complement the ongoing trial on PD0332991 by acquiring information on its clinical activity in post-menopausal patients with ER positive, Her2 negative advanced breast cancer patients already pretreated with a first-line or second line endocrine therapy.
Interventions
DRUGPalbociclib
Palbociclib 125 mg/day orally in an ongoing 3:1 schedule (3 weeks on/1 week off)
DRUGAnastrozole
Continuation of prior anastrozole 1mg/day orally in a continuous regimen
DRUGLetrozole
Continuation of prior letrozole 2.5mg/day orally in a continuous regimen
DRUGExemestane
Continuation of prior exemestane 25mg/day orally in a continuous regimen
DRUGFulvestrant
Continuation of prior fulvestrant 500mg intramuscular injection every 4 weeks in a continuous regimen
Sponsors
Fondazione Sandro Pitigliani
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically proven diagnosis of adenocarcinoma of the breast with evidence of metastatic disease * ER positive tumor ≥ 10% * HER2 negative breast cancer by FISH or IHC * Progression of advanced breast cancer on first or second line endocrine therapy for advanced breast cancer * Paraffin-embedded tumor available for centralized assessment of biomarkers * Measurable disease according to RECIST 1.1 (bone only disease is allowed only if measurable). * Postmenopausal status * Eastern Cooperative Oncology Group (ECOG) Performance status 0 -2 * Resolution of all acute toxic effects of prior therapy or surgical procedures to CTCAE grade \>1 * Adequate organ function
Exclusion criteria
* Unstable brain metastases * Prior treatment with more than one line of CT or more than two lines of HT advanced breast cancer or any CDK inhibitor * Current treatment with therapeutic doses of anticoagulant * Current use or anticipated need for food or drugs that are known strong CYP3A4 inhibitors / inducers, drugs that are predominantly metabolized by CYP3A with narrow therapeutic indices, drugs with the potential of prolonging QT interval * Diagnosis of any secondary malignancy within the last 3 years * Active inflammatory bowel disease or chronic diarrhea * Known human immunodeficiency virus infection; active hepatitis C, active hepatitis B
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of complete response (CR), partial response (PR) or stable disease (SD) ≥24 weeks (clinical benefit) | Baseline up to 3 years | All randomized patients with adequate baseline disease assessment with measurable disease, the disease under study and who start treatment on the assigned arm will be considered evaluable for clinical benefit (CB). The probability of CB on each randomized treatment arm will be estimated by dividing the number of patients with CB by the number of evaluable patients randomized to the treatment arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival (PFS) | Baseline up to 3 years | PFS is the time from randomization date to date of first documentation of progression or death due to any cause, whichever occurs first. Documentation of progression must be by objective disease assessment as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. All patients randomized will be considered evaluable for PFS. |
| Objective Response (OR) | Baseline up to 3 years | All randomized patients with adequate baseline disease assessment with measurable disease, the disease under study and who start treatment on the assigned arm will be considered evaluable for objective response (CR or PR). The probability of OR on each randomized treatment arm will be estimated by dividing the number of patients with OR by the number of evaluable patients randomized to the respective treatment arm (response rate). |
| Time to Progression (TTP) | Baseline up to 3 years | TTP is the time from randomization date to date of first documentation of objective progression. All patients randomized will be considered evaluable for TTP. |
| Duration of Response (DR) | Baseline up to 3 years | For patients with an objective response (CR or PR), duration of response is the time from first documentation of CR or PR to date of first documentation of objective progression or death. Date of first documentation of progression and date of first documentation of CR or PR will be based on investigator assessment of response. |
| Overall Survival (OS) | Baseline up to 6 years | OS is the time from randomization date to date of death due to any cause. All patients randomized will be considered evaluable for OS. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events | Baseline up to 3 years | All patients treated with at least one dose of trial treatment will be included in safety analyses. Adverse events will be summarized by treatment and by the frequency of patients experiencing treatment emergent adverse events corresponding to body systems and MedDRA preferred term. Adverse events will be graded by worst NCI CTCAE v4.0 grade. |
Countries
Italy
Outcome results
None listed