Breast Cancer
Conditions
Brief summary
The purpose of this study is to determine if the combination of endocrine therapy and Palbociclib at a daily dose of 100 mg will result in a better response to therapy with fewer dose interruptions than the proposed dosing regimen of 125 mg daily for 21 days out of a 28 day cycle in combination with endocrine therapy.
Detailed description
The standard or usual treatment of this type of breast cancer is endocrine therapy. Palbociclib is a new type of drug for breast cancer. Laboratory tests as well as studies in animals and people show that it may help slow the growth of breast cancer. The most widely tested regimen of Palbociclib for patients with metastatic/advanced breast cancer is 125 mg every day for 21 days out of a 28 day cycle in combination with standard endocrine (hormone) therapy. This study explores if administering a lower dose of palbociclib - 100 mg given every day of a 28 day cycle in combination with standard endocrine (hormone) therapy - may result in more tumour shrinkage and be better tolerated.
Interventions
100mg PO daily
125mg PO daily 3 weeks out of 4
DRUGFulvestrant or Tamoxifen or Aromatase Inhibitor
given at the standard doses/schedules
Sponsors
Pfizer
Canadian Cancer Trials Group
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
* Premenopausal and postmenopausal women 18 years of age or older. * Histologically confirmed adenocarcinoma of the breast, with ER positive and HER2 negative status based on local testing on most recent pathological tumour specimen. * Patients must satisfy the following criteria for prior therapy: * Progressed during treatment or within 12 months of completion of adjuvant endocrine therapy or * Progressed during prior endocrine therapy for advanced/metastatic disease. Note: 'Progressed during endocrine therapy' means that the patient progressed while on or within 1 month after discontinuation of endocrine therapy. * One line of chemotherapy for advanced/metastatic disease (regardless of prior adjuvant chemotherapy use) is allowed in addition to endocrine therapy. * Patients must have evidence of disease to be eligible for the study, but measurable disease is not mandatory. * For those patient with measureable disease who will be included in the response assessment, the following criteria must apply: * X-ray ≥ 20 mm * Spiral CT scan or physical exam ≥ 10 mm (lymph nodes must be ≥ 15 mm in the short axis) * Conventional CT scan, MRI ≥ 20 mm * Measurable lesions must be outside a previous radiotherapy field if they are the sole site of disease, unless disease progression has been documented. Tumor lesions previously irradiated or subjected to other loco regional therapy will only be deemed measurable if progression at the treated site after completion of therapy is clearly documented. * Eastern Cooperative Oncology Group (ECOG) 0-2. * Adequate organ and bone marrow function as defined by: * ANC ≥ 1,500/mm3 (1.5 x 109/L) * Platelets ≥ 100,000/mm3 (100 x 109/L) * Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥60 ml/min as calculated using the method standard for the institution; * Total serum bilirubin ≤ 1.5 x ULN (\<3 ULN if Gilbert's disease). * Patient must agree to provide tumour tissue from the most recent pathological tumour specimen. * Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires in either English or French * Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate * Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating centre. This implies there must be reasonable geographical limits placed on patients being considered for this trial. * In accordance with NCIC CTG policy, protocol treatment is to begin within 2 working days of patient randomization. * Women of childbearing potential must have agreed to use a highly effective contraceptive method.
Exclusion criteria
* Patients with advanced, symptomatic, visceral spread that are at risk of life threatening complication in the short term. * Patients with symptomatic CNS involvement, meningeal or parenchymal, that is uncontrolled or requires steroids. * Prior treatment with any CDK 4/6 inhibitor. * Prior treatment with mTOR inhibitors. * Active second malignancy, regardless of ongoing treatment. * Any concurrent medical condition that in the opinion of the investigator would interfere with the safe administration of the study drug and participation in the study. * Participation in a prior anti-cancer investigational study within 30 days prior to enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival Using the RECIST 1.1 Criteria | 2 years | progression free survival (PFS) is defined as time from randomization to progression or death from any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Response or No Response | 2 years | Response rate = Number of (Complete response + partial response) / total treated patients. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
| Duration of Response | 2 years | For patients with complete or partial response, duration of response is defined as days from first recorded response to the first date of recurrent or progression or death. |
| Overall Survival | 2 years | Time from randomization to death of any cause. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Palbociclib (100mg) Palbociclib 100mg PO daily plus Fulvestrant or Tamoxifen or another Aromatase Inhibitor at the standard doses/schedules
Palbociclib 100mg: 100mg PO daily
Fulvestrant or Tamoxifen or Aromatase Inhibitor: given at the standard doses/schedules | 90 |
| Palbociclib (125mg) Palbociclib 125mg PO daily 3 out of 4 weeks plus Fulvestrant or Tamoxifen or another Aromatase Inhibitor at the standard doses/schedules
Palbociclib 125mg: 125mg PO daily 3 weeks out of 4
Fulvestrant or Tamoxifen or Aromatase Inhibitor: given at the standard doses/schedules | 90 |
| Total | 180 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | No receive treatment | 0 | 1 |
Baseline characteristics
| Characteristic | Palbociclib (100mg) | Total | Palbociclib (125mg) |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 38 Participants | 68 Participants | 30 Participants |
| Age, Categorical Between 18 and 65 years | 52 Participants | 112 Participants | 60 Participants |
| Age, Continuous | 61.5 years | 60.5 years | 59.5 years |
| Menopausal Status Postmenopausal | 83 Participants | 163 Participants | 80 Participants |
| Menopausal Status Premenopausal | 7 Participants | 17 Participants | 10 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 10 Participants | 16 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 8 Participants | 6 Participants |
| Race (NIH/OMB) White | 76 Participants | 151 Participants | 75 Participants |
| Region of Enrollment Canada | 90 participants | 180 participants | 90 participants |
| Sex: Female, Male Female | 90 Participants | 180 Participants | 90 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 29 / 90 | 32 / 89 |
| other Total, other adverse events | 89 / 90 | 88 / 89 |
| serious Total, serious adverse events | 9 / 90 | 12 / 89 |
Outcome results
Primary
Progression Free Survival Using the RECIST 1.1 Criteria
progression free survival (PFS) is defined as time from randomization to progression or death from any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: 2 years
Population: Intend to treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Palbociclib (100mg) | Progression Free Survival Using the RECIST 1.1 Criteria | 9.33 months |
| Palbociclib (125mg) | Progression Free Survival Using the RECIST 1.1 Criteria | 11.30 months |
90% CI: [0.66, 1.3]
Secondary
Duration of Response
For patients with complete or partial response, duration of response is defined as days from first recorded response to the first date of recurrent or progression or death.
Time frame: 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Palbociclib (100mg) | Duration of Response | 126 days |
| Palbociclib (125mg) | Duration of Response | 169 days |
Secondary
Number of Participants With Response or No Response
Response rate = Number of (Complete response + partial response) / total treated patients. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: 2 years
Population: Only patients received protocol treatment were included in this analysis
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Palbociclib (100mg) | Number of Participants With Response or No Response | Response | 10 Participants |
| Palbociclib (100mg) | Number of Participants With Response or No Response | No response | 80 Participants |
| Palbociclib (125mg) | Number of Participants With Response or No Response | Response | 11 Participants |
| Palbociclib (125mg) | Number of Participants With Response or No Response | No response | 78 Participants |
Secondary
Overall Survival
Time from randomization to death of any cause.
Time frame: 2 years
Population: Intend to treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Palbociclib (100mg) | Overall Survival | 20.73 months |
| Palbociclib (125mg) | Overall Survival | 21.39 months |
90% CI: [0.67, 1.69]