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 | 20.1 |
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 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
Patients must be affiliated to a Social Security System (or equivalent)
Patient must have signed a written informed consent prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient’s consent
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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 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
Participation in another therapeutic trial within the 30 days prior to randomization
Persons deprived of their liberty or under protective custody or guardianship
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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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
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 | 6 |
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 |