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
(national): 10/2020
Coordinating Investigator: Balic, Marija; Graz
Patient Accrual: 400 (global), 50 (national)
Study Design:
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Arm A

  • 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

Arm B

  • 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.

Primary Objective:

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.

Secondary Objectives:

  • 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.

Inclusion Criteria:

  1. 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:
    – Breast
    – Chest wall including mastectomy scar and/or skin
    – Axillary or internal mammary lymph nodes
  2. 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
  3. Negative or microscopically involved margins
  4. Female or male aged 18 years or older
  5. ECOG performance status 0 or 1
  6. Recurrent tumor must be hormone receptor positive: ER+ and/or PgR+ ≥1% by IHC
  7. 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
  8. Normal hematologic status:
    – Absolute neutrophil count ≥1000/mm3 (1.0× 109/L)
    – Platelets ≥100× 109/L
    – Hemoglobin ≥9 g/dL (≥90 g/L)
  9. Normal renal function:
    – Serum creatinine ≤1.5 ULN
  10. 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
  11. 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).
  12. The patient has been informed of and agrees to data transfer and handling, in accordance with national data protection guidelines.
  13. The patient agrees to make tumor (diagnostic core biopsy or surgical specimen of ILRR) available for submission for central pathology review
  14. Patients must either be planned to initiate, or have already started, endocrine therapy
  15. 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).

Exclusion Criteria:

  1. Recurrence of any size with direct extension to the chest wall and/or to the skin (ulceration or skin nodules) not surgically removable
  2. 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)
  3. Bilateral synchronous or metachronous invasive breast cancer (in situ carcinoma of the contralateral breast is allowed)
  4. Inflammatory breast cancer
  5. 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.
  6. Previous treatment with palbociclib or any other CDK 4/6 inhibitors
  7. Previous or planned chemotherapy or radiotherapy for the ipsilateral isolated locoregional recurrence (radiotherapy must be completed more than 2 weeks prior to randomization).
  8. 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.
  9. Pregnant or lactating women; lactation has to stop before randomization
  10. Patients with psychiatric illness/social situations that would limit compliance with study requirements.
  11. Contraindications or known hypersensitivity to the palbociclib or excipients
  12. 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

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