ABCSG 49 Study Details *
A phase III open-label, multicenter, randomized trial of adjuvant palbociclib in combination with endocrine therapy versus endocrine therapy alone for patients with hormone receptor positive / HER2-negative resected isolated locoregional recurrence of breast cancer
|Study start :||(global): 08/2019
|Coordinating Investigator:||Balic, Marija; Graz|
|Patient Accrual:||400 (global), 50 (national)|
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- Palbociclib 125 mg/day orally for 21 days, followed by 7 days rest for 3 years from randomization.
- Standard endocrine therapy for at least 3 years from randomization
- Standard endocrine therapy for at least 3 years from randomization
Randomization must take place within 6 months from the complete gross excision of the locoregional recurrence.
Radiotherapy (if given) for the ipsilateral locoregional recurrence must be completed more than 2 weeks prior to randomization.
To determine whether treatment with 3 years of palbociclib plus standard endocrine therapy for at least 3 years prolongs invasive disease-free survival (iDFS) compared to treatment with standard endocrine therapy alone for at least 3 years in patients with hormone receptor positive, HER2-negative resected isolated locoregional recurrence (ILRR) of breast cancer.
- To assess tolerability of 3 years of palbociclib in combination with standard endocrine therapy compared to standard endocrine therapy alone, as measured by adverse events.
- To assess whether treatment with 3 years of palbociclib plus standard endocrine therapy for at least 3 years prolongs other measures of efficacy as compared to treatment with standard endocrine therapy alone for at least 3 years in this patient population.
- Histologically confirmed invasive breast cancer, defined as first proven ipsilateral local and/or regional recurrence of a primary invasive breast cancer in at least one of the sites below:
– Chest wall including mastectomy scar and/or skin
– Axillary or internal mammary lymph nodes
- Completion of locoregional therapy:
– Completion of gross excision of recurrence within 6 months prior to randomization
– Completion of radiotherapy (if given) more than 2 weeks prior to randomization
- Negative or microscopically involved margins
- Female or male aged 18 years or older
- ECOG performance status 0 or 1
- Recurrent tumor must be hormone receptor positive: ER+ and/or PgR+ ≥1% by IHC
- Recurrent tumor must be HER2-negative (0, 1+, 2+ by IHC and/or ISH/FISH not amplified)
Tumor with HER2 status 2+ by IHC must also be negative (not amplified) by ISH/FISH
- Normal hematologic status:
– Absolute neutrophil count ≥1000/mm3 (1.0× 109/L)
– Platelets ≥100× 109/L
– Hemoglobin ≥9 g/dL (≥90 g/L)
- Normal renal function:
– Serum creatinine ≤1.5 ULN
- Normal liver function:
– Serum total bilirubin ≤1.5× upper limit of normal (ULN). In the case of known Gilbert’s syndrome, a higher serum total bilirubin (<2× ULN) is allowed
– AST and ALT ≤2.5× ULN
– Alkaline phosphatase ≤2.5× ULN
- Women of childbearing potential must have a documented negative pregnancy test within 7 calendar days prior to randomization.
Women of childbearing potential, and sexually active men must agree to effective non-hormonal contraception after the pregnancy test and during the protocol treatment phase (see Section 9.6 for highly effective contraception methods).
- The patient has been informed of and agrees to data transfer and handling, in accordance with national data protection guidelines.
- The patient agrees to make tumor (diagnostic core biopsy or surgical specimen of ILRR) available for submission for central pathology review
- Patients must either be planned to initiate, or have already started, endocrine therapy
- Written Informed Consent (IC) must be signed and dated by the patient and the Investigator prior to randomization (may be obtained more than 28 calendar days prior to randomization).
- Recurrence of any size with direct extension to the chest wall and/or to the skin (ulceration or skin nodules) not surgically removable
- Evidence of distant metastasis as based on conventional staging examinations (physical, chest X-ray or CT, abdominal ultrasound or CT, bone scintigraphy or FDG-PET-CT)
- Bilateral synchronous or metachronous invasive breast cancer (in situ carcinoma of the contralateral breast is allowed)
- Inflammatory breast cancer
- Patients with a history of malignancy, other than invasive breast cancer with the following exceptions:
– Patients diagnosed, treated and disease-free for at least 5 years and deemed by the investigator to be at low risk for recurrence of that malignancy are eligible
– Patients with the following malignancies are eligible, even if diagnosed and treated within the past 5 years: ductal carcinoma in situ of the breast; cervical cancer in situ; thyroid cancer in situ; non-metastatic, non-melanomatous skin cancer.
- Previous treatment with palbociclib or any other CDK 4/6 inhibitors
- Previous or planned chemotherapy or radiotherapy for the ipsilateral isolated locoregional recurrence (radiotherapy must be completed more than 2 weeks prior to randomization).
- Concurrent disease or condition that would make the patient inappropriate for trial participation or any serious medical disorder that would interfere with the patient’s safety, such as: known history of uncontrolled or symptomatic angina, clinically significant arrhythmias, congestive heart failure, transmural myocardial infarction, uncontrolled hypertension (≥180/110), unstable diabetes mellitus, dyspnea at rest, or chronic therapy with oxygen, etc.
– Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association (NYHA) Functional Classification. To be eligible for this trial, patients should be class 2B or better.
– Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
– For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
– Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
- Pregnant or lactating women; lactation has to stop before randomization
- Patients with psychiatric illness/social situations that would limit compliance with study requirements.
- Contraindications or known hypersensitivity to the palbociclib or excipients
- History of extensive disseminated/bilateral or known presence of interstitial fibrosis or interstitial lung disease, including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, obliterative bronchiolitis, and pulmonary fibrosis. A history of prior radiation pneumonitis is not considered an exclusion criterion.
* studyinformation based on protocol version 2.0