A phase III clinical trial, which tests the safety and efficacy of the combination of palbociclib and endocrine therapy to learn whether the combination of these drugs works for a specific form of breast cancer (hormone receptor positive / HER2-negative isolated locoregional recurrent breast cancer).

Phase 1

Conditions: patients with hormone receptor positive / HER2-negative resected isolated locoregional recurrence of breast cancer
MedDRA version: 20.0Level: PTClassification code 10006198Term: Breast cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.1Level: LLTClassification code 10070575Term: Estrogen receptor positive breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2018-003553-19-HU

Lead Sponsor: International Breat Cancer Study Group (IBCSG)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 400

Inclusion Criteria

? Histologically confirmed invasive breast cancer, defined as first proven ipsilateral local and/or regional recurrence in at least one of the sites below:
– Breast
– 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 hematological, renal, and liver function
? 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 for ipsilateral isolated locoregional recurrence
? Written Informed Consent (IC) prior to randomization
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 200

Exclusion Criteria

? 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 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 cancers
? Previous treatment with palbociclib or any other CDK 4/6 inhibitors
? Previous or planned chemotherapy or planned radiotherapy for the ipsilateral isolated locoregional recurrence (radiotherapy is allowed, but must be completed more than 2 weeks prior to randomization)
? Concurrent disease or condition that would make the patient inappropriate for study participation or any serious medical disorder that would interfere with the patient’s safety
? Contraindications or known hypersensitivity to the palbociclib or excipients
? Pregnant or lactating women; lactation has to stop before randomization

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine whether treatment with 3 years of palbociclib plus standard endocrine therapy for at least 3 years prolongs iDFS compared to treatment with standard endocrine therapy alone for at least 3 years in patients with HR-positive / HER2-negative resected isolated locoregional recurrence (ILRR) of breast cancer.;Secondary Objective: To assess the tolerability of 3 years of palbociclib in combination with standard endocrine therapy compared to standard endocrine therapy alone, as measured by adverse events.<br>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.;Primary end point(s): Invasive disease-free survival (iDFS);Timepoint(s) of evaluation of this end point: from randomization until first appearance of invasive local, regional, or distant recurrence

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Tolerability: Adverse events<br>- Breast cancer-free interval (BCFI)<br>- Distant recurrence-free interval (DRFI)<br>- Overall survival (OS);Timepoint(s) of evaluation of this end point: -Adverse events: at occurance , from randomization until end of treatment visit<br>- BCFI: time from randomization until first appearance of invasive local, regional, or distant recurrence<br>- DRFI: time from randomization until first appearance of distant recurrence of breast cancer<br>- OS: time from randomization until death from any cause

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