Phase 2,Open-label,Multicenter,Randomized Study of PD0332991 (Oral CDK4/6 Inhibitor) Monotherapy and in Combination With the HT to Which the pt Has Progressed in the Previous Line for ER+,Her2- Post-menopausal Advanced Breast Cancer Pts
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Enrollment
- 115
- Locations
- 6
- Primary Endpoint
- Incidence of complete response (CR), partial response (PR) or stable disease (SD) ≥24 weeks (clinical benefit)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts 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
Arms & Interventions
Arm B
Palbociclib + HT (Anastrozole, Letrozole, Exemestane, Fulvestrant)
Intervention: Anastrozole (Drug)
Arm A
Palbociclib monoterapy
Intervention: Palbociclib (Drug)
Arm B
Palbociclib + HT (Anastrozole, Letrozole, Exemestane, Fulvestrant)
Intervention: Palbociclib (Drug)
Arm B
Palbociclib + HT (Anastrozole, Letrozole, Exemestane, Fulvestrant)
Intervention: Letrozole (Drug)
Arm B
Palbociclib + HT (Anastrozole, Letrozole, Exemestane, Fulvestrant)
Intervention: Exemestane (Drug)
Arm B
Palbociclib + HT (Anastrozole, Letrozole, Exemestane, Fulvestrant)
Intervention: Fulvestrant (Drug)
Outcomes
Primary Outcomes
Incidence of complete response (CR), partial response (PR) or stable disease (SD) ≥24 weeks (clinical benefit)
Time Frame: 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 Outcomes
- Overall Survival (OS)(Baseline up to 6 years)
- Progression free survival (PFS)(Baseline up to 3 years)
- Time to Progression (TTP)(Baseline up to 3 years)
- Objective Response (OR)(Baseline up to 3 years)
- Duration of Response (DR)(Baseline up to 3 years)