PALbociclib CoLlaborative Adjuvant Study:A randomized phase III trial of Palbociclib with standard adjuvantendocrine therapy versus standard adjuvant endocrine therapy alone forhormone receptor positive/HER2-negative early breast cancer
- Conditions
- To determine whether the addition of palbociclib to adjuvant endocrine therapy will improve outcomes over endocrine therapy alone for HR+/HER2- early breast cancer.MedDRA version: 23.0Level: LLTClassification code 10070575Term: Estrogen receptor positive breast cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-005181-30-IT
- Lead Sponsor
- ABCSG GMBH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 5600
1-signed Informed consent(2)Age =18 ys. (3)Pre and postmenopausal women or men with Stage II (Stage IIA limited to a max. of 1000 patients) or Stage III early invasive breast cancer per AJCC Breast Cancer Staging version 7 /UICC.(4) Pts with multicentric and/or multifocal and/or bilateral early invasive breast cancer whose histopathologically examined tumors all meet pathologic criteria for ER+ and/or PR+ and HER2. (5)Pts must have histologically confirmed hormone receptor positive (ER+ and/or PR+), HER2-, early invasive breast cancer. ER, PR and HER2 measurement in a CLIA-approved setting in the US or certified laboratories for Non-US regions. Cut-off values for positive/negative staining should be in accordance with current ASCO/CAP guidelines. Pts with equivocal HER2 in situ hybridization results according to current ASCO/CAP guidelines are eligible, as long as they have not received and are not scheduled to receive anti-HER2 treatment. Testing may occur on diagnostic core or surgical tumor tissue.(6)Pts must have undergone breast surgery for the current malignancy.7)A formalin-fixed paraffin-embedded (FFPE) tumor tissue block must be transmitted to a central sample repository and confirmation of receipt must be available prior to randomization.(8) ECOG performance status 0-1.(9)Pts able and willing to swallow and retain oral medication without a condition that would interfere with enteric absorption.(10) Serum or urine pregnancy test negative within 7 days of randomization. Pregnancy testing does not need to be pursued in pts who are judged as postmenopausal before randomization, or who undergone bilateral ophorectomy, total hysterectomy, or bilateral tubal ligation. Women of childbearing potential and male pts randomized into treatment Arm A or B must use adequate contraception for the duration of protocol treatment and for 6 months after the last treatment with palbociclib if they are in arm A. Pts receiving standard adjuvant endocrine therapy (Arm A and Arm B) should use adequate contraception in accordance with the specific medication requirements.(11)Pts may or may not have received neo/adjuvant therapy, but must be after last dose of chemotherapy and/or biologic therapy and must have sufficient resolution of side effects at randomization.(12)Patients may or not have received breast/axilla/postmastectomy chest wall radiotherapy, but must be after last dose of radiotherapy and must have sufficient resolution of side effects at randomization.(13)Patients must have sufficient resolution of any surgical side effects from the last surgery at the randomization.(14)Patients must either be initiating or have already started adjuvant hormonal treatment. Patients may already have initiated endocrine therapy at the time of randomization, but randomization must take place within 12 months of date of histological diagnosis and within 6 months of initiating standard adjuvant endocrine therapy. Pts who received neoadjuvant endocrine therapy are eligible as long as they are enrolled within 12 months of initial histological diagnosis and after completing no more than 6 months of adjuvant endocrine therapy. Patients may be receiving tamoxifen or aromatase inhibitor. For premenopausal and men, concurrent LHRH agonist use allowable and be ongoing at randomization. If a LHRH agonist used for ovarian protection during neo/adjuvant chemotherapy it is allowable and shall not be taken into account x calculations reg the 6 months standard adjuvant endo
(1) Concurrent therapy with other Investigational Products.
(2) Prior therapy with any CDK inhibitor.
(3) Patients with Stage I or IV breast cancer are not eligible. Baseline staging to document absence of metastatic disease is not required, however is recommended as determined by institutional practice.
(4) History of allergic reactions attributed to compounds of chemical or biologic composition similar to palbociclib.
(5) Patients receiving any medications or substances that are potent inhibitors or inducers of CYP3A isoenzymes within 7 days of randomization.
(6) Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, diabetes, or psychiatric illness/social situations that would limit compliance with study requirements. Ability to comply with study requirements is to be assessed by each investigator at the time of screening for study participation.
(7) Pregnant women, or women of childbearing potential without a negative pregnancy test (serum or urine) within 7 days prior to randomization, irrespective of the method of contraception used, are excluded from this study because the effect of palbociclib on a developing fetus is unknown. Breastfeeding must be discontinued prior to study entry.
(8) Patients with a history of any malignancy are ineligible except for the following circumstances:
• Patients with a malignancy history other than invasive breast cancer are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy.
• Patients with the following cancers are eligible, even if diagnosed and treated within the past 5 years: ductal carcinoma in situ of the breast, cervical cancer in situ, and non-metastatic non-melanomatous skin cancer.
(9) Patients are not eligible if they have previously received endocrine therapy within 5 years prior to diagnosis of the current malignancy. This includes use for prophylactic reasons, including treatment of osteoporosis or cancer prevention with tamoxifen, raloxifene or AI.
Patients may concurrently receive bisphosphonates or rank ligand inhibitors while on this study if necessary for treatment or prevention of osteopenia or osteoporosis. (10) Patients on combination antiretroviral therapy, i.e. those who are
HIV-positive, are ineligible because of the potential for pharmacokinetic interactions or increased immunosuppression with palbociclib.
(11) Patients with clinically significant chronic history of liver disease, including chronic/active viral or other known hepatitis, current alcohol abuse, or cirrhosis, etc.
(12) Patients receiving concurrent exogenous hormone therapy (hormone replacement therapy, oral or any other hormonal contraceptives such as hormonal contraceptive coil, etc.) are not eligible but topical vaginal estrogen therapy is allowable.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method