A phase III study comparing the concurrent versus the sequential administration of chemotherapy and aromatase inhibitors, as adjuvant treatment of post-menopausal patients with endocrine-responsive early breast cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

IRCCS Ospedale Policlinico San Martino

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2025-02-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

ITALIAN MINISTRY OF HEALTH

External identifiers

EU CT number

2024-519087-41-00

EudraCT number

2013-001629-23

ClinicalTrials.gov

NCT02918084

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate the relative efficacy of sequential as compared to concurrent administration of chemotherapy and aromatase inhibitors in patients with early breast cancer in the prevention of disease recurrence.

Secondary objectives 1

1. To evaluate the relative efficacy of the two treatment strategies on overall mortality, local relapses, distant relapses, and to compare their toxicity.

Conditions and MedDRA coding

Breast cancer is the most common form of cancer among women in North America, Europe and Latin America. Beacause nearly 80% of breast cancers are endocrine-responsive tumors, the majority of patients candidates for adjuvant chemotherapy (CT) are also candidates for endocrine therapy (ET).The optimal timing (i.e. concomitant vs sequential administration) for the integration of these two treatments has not been clearly defined yet.

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. - Women with histological diagnosis of invasive breast cancer completely removed by surgery, any T, any N. - Postmenopausal status defined by at least one of the following conditions: 1. Aged = 60 2. Aged 45-59 and satisfying one or more of the following criteria • amenorrhea for =12 months and intact uterus; • amenorrhea for <12 months and FSH within the postmenopausal range, including: > pts with hysterectomy > pts who have received HRT > pts with chemotherapy-induced amenorrhea 3. bilateral oophorectomy at any age >18 years. - Primary tumor positive for ER and/or PgR (=1% tumor cells positive by immunohistochemistry or = 10 fmol/mg cytosol protein by ligand binding assay). - Patients who are prescribed 5 years of endocrine therapy with an AI - Indication for adjuvant chemotherapy- Patients with HER-2 positive tumors are eligible provided that they are prescribed trastuzumab according to registered schedule. - Signed informed consent.

Exclusion criteria 1

1. - HRT currently assumed or during the month before randomization - Recurrent or metastatic disease - HER-2 positive tumors if treatment with trastuzumab is considered not appropriate/feasible - Concurrent illness that contraindicate adjuvant endocrine treatment and/or chemotherapy - Patients who have received TAM as part of any breast cancer prevention trial - Previous history of invasive breast cancer or other invasive malignancy within the previous 10 years, other than squamous or basal cell carcinoma of the skin or carcinoma in situ of the cervix, adequately cone biopsied - Concomitant severe disease which would place the patient at unusual risk - Concurrent treatment with experimental drugs - Patients treated with systemic investigational drugs within the past 30 days

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. According to the STEEP system (Hudis et al. J Clin Oncol 2007; 25:2127-2132) the primary endpoint will be the so called DFS, defined as time elapsing between the date of randomization and the date of one of the following events, whichever occurs first - Local Recurrence of disease - Regional recurrence of disease - Distant recurrence of disease - Contralateral invasive or intraductal breast cancer - Second primary malignancy other than breast - Death for any cause

Secondary endpoints 3

1. the OS defined as time elapsing between the date of randomization and the date of death for any cause
2. all the other outcomes defined within the STEEP system
3. safety: clinical and laboratory toxicities will be graded according to NCI criteria CTCAE

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

IRCCS Ospedale Policlinico San Martino

Sponsor organisation

IRCCS Ospedale Policlinico San Martino

Address

Largo Rosanna Benzi 10

City

Genoa

Postcode

16132

Country

Italy

Scientific contact point

Organisation

IRCCS Ospedale Policlinico San Martino

Contact name

Lucia Del Mastro

Public contact point

Organisation

IRCCS Ospedale Policlinico San Martino

Contact name

Lucia Del Mastro

Locations

1 EU/EEA country · 50 investigational sites

By country

Investigational sites

Results and documents

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

Documents 10 files

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

Application history

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