Palbociclib for HR positive Isolated Local or Regional Recurrence of Breast Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

ETOP IBCSG Partners Foundation

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

25 Oct 2019 → ongoing

Decision date (initial)

2024-04-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Pfizer SRL

External identifiers

EU CT number

2024-510776-20-00

EudraCT number

2018-003553-19

ClinicalTrials.gov

NCT03820830

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

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 objectives 1

1. 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.

Conditions and MedDRA coding

Female or male patients with histologically confirmed HR-positive, HER2-negative resected isolated locoregional recurrence (ILRR) of breast cancer.

Study design 4 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

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 - 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

Exclusion criteria 1

1. - 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 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint iDFS is defined as duration of time from randomization until first appearance of invasive local, regional, or distant recurrence (including invasive ipsilateral breast tumor recurrence), invasive contralateral breast cancer, a second (non-breast) invasive cancer, or death from any cause.

Secondary endpoints 1

1. The secondary endpoints are: - Adverse events, according to CTCAE version 5 - Breast cancer-free interval (BCFI) - Distant recurrence-free interval (DRFI) - Overall survival (OS)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

ETOP IBCSG Partners Foundation

Sponsor organisation

ETOP IBCSG Partners Foundation

Address

Effingerstrasse 33

City

Bern

Postcode

3008

Country

Switzerland

Scientific contact point

Organisation

ETOP IBCSG Partners Foundation

Contact name

ETOP IBCSG Partners Regulatory Office

Public contact point

Organisation

ETOP IBCSG Partners Foundation

Contact name

ETOP IBCSG Partners Regulatory Office

Third parties 4

Locations

5 EU/EEA countries · 38 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 73 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications