E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
patients with hormone receptor positive / HER2-negative resected isolated locoregional recurrence of breast cancer |
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E.1.1.1 | Medical condition in easily understood language |
Patients with breast cancer in the operated breast, the surgical scar, the chest wall or the regional lymph nodes |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10006198 |
E.1.2 | Term | Breast cancer recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10070575 |
E.1.2 | Term | Estrogen receptor positive breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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. 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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
● 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 ● 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 |
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E.4 | Principal 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 synchromous 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 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 ● 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. History of prior radiation pneumonitis is not an exclusion criterion. ● Pregnant or lactating women; lactation has to stop before randomization |
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E.5 End points |
E.5.1 | Primary end point(s) |
Invasive disease-free survival (iDFS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
from randomization until first appearance of invasive local, regional, or distant recurrence |
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E.5.2 | Secondary end point(s) |
- Tolerability: Adverse events - Breast cancer-free interval (BCFI) - Distant recurrence-free interval (DRFI) - Overall survival (OS) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
-Adverse events: at occurance , from randomization until end of treatment visit - BCFI: time from randomization until first appearance of invasive local, regional, or distant recurrence - DRFI: time from randomization until first appearance of distant recurrence of breast cancer - OS: time from randomization until death from any cause |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
France |
Hungary |
Italy |
Spain |
Switzerland |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 6 |