Optimizing Extended Adjuvant Endocrine Therapy in Patients With Breast Cancer

NCT06223698 | Not Yet Recruiting Phase 3

• 1 other identifier: 280050
• Study Type: interventional
• Target: 3,832
• Locations: 1 country
• Sites: 15

Brief Summary

Based on the risk of late recurrence in breast cancer patients with luminal disease with high-risk for recurrence, extended adjuvant endocrine therapy beyond 5 years is recommended as a valid treatment option. In premenopausal women at diagnosis converted to postmenopausal after the first five years of tamoxifen, two treatment strategies for extended adjuvant endocrine therapy are available, namely continuing with tamoxifen or switching to aromatase inhibitors (AI). No randomized evidence does exist and both treatment strategies are used in clinical practice. In postmenopausal women with higher recurrence risk initially treated with AI for five years, extended adjuvant therapy with additional two years of AI has shown to be as effective as additional five years of AI. However, no randomized evidence on whether a switching strategy of five-year extended tamoxifen is better compared to two-year extended AI is available. Both treatment strategies are used in clinical practice. The primary objective of this register-based randomized trial is to investigate the overall survival between patients treated with switching strategy for extended adjuvant endocrine therapy compared to continuing with the same treatment as the initial 5 years in two different clinical scenarios:

• In premenopausal women at diagnosis who converted to postmenopausal after 5 years of tamoxifen.
• In postmenopausal women at diagnosis.

Conditions

Breast Cancer

Keywords

breast cancer; adjuvant therapy; endocrine treatment; extended therapy

Outcome Measures

Primary Outcomes (1)

• Overall survival

  120 months

Secondary Outcomes (8)

• Invasive disease-free survival

  36 months; 60 months; 120 months

• Distant disease-free survival

  36 months; 60 months; 120 months

• Breast cancer-specific survival

  36 months; 60 months; 120 months

• Overall survival

  36 months; 60 months

• Frequency of selected grade 3/4 toxicities

  36 months; 60 months; 120 months

Study Arms (4)

Cohort 1: Aromatase inhibitors for 5 years

EXPERIMENTAL

Cohort 1 (premenopausal at diagnosis =\> postmenopausal at randomization) 5-year tamoxifen =\> Randomized to Arm A (switching to aromatase inhibitors for 5 years).

Drug: Letrozole; Drug: Anastrozole; Drug: Exemestane

Cohort 1: Tamoxifen for 5 years

ACTIVE COMPARATOR

Cohort 1 (premenopausal at diagnosis =\> postmenopausal at randomization) 5-year tamoxifen =\> Randomized to Arm B (continuing with tamoxifen for 5 years).

Drug: Tamoxifen

Cohort 2: Tamoxifen for 5 years

EXPERIMENTAL

Cohort 2 (postmenopausal at diagnosis) 5-year aromatase inhibitors =\> Randomized to Arm A (switching to tamoxifen for 5 years).

Drug: Tamoxifen

Cohort 2: Aromatase inhibitors for 2 years

ACTIVE COMPARATOR

Cohort 2 (postmenopausal at diagnosis) 5-year aromatase inhibitors =\> Randomized to Arm B (continuing with AI for 2 years).

Drug: Letrozole; Drug: Anastrozole; Drug: Exemestane

Interventions

Letrozole DRUG

Letrozole 2.5 mg daily

Cohort 1: Aromatase inhibitors for 5 years; Cohort 2: Aromatase inhibitors for 2 years

Anastrozole DRUG

Anastrozole 1 mg daily

Cohort 1: Aromatase inhibitors for 5 years; Cohort 2: Aromatase inhibitors for 2 years

Exemestane DRUG

Exemestane 25 mg daily

Cohort 1: Aromatase inhibitors for 5 years; Cohort 2: Aromatase inhibitors for 2 years

Tamoxifen DRUG

Tamoxifen 20 mg daily

Cohort 1: Tamoxifen for 5 years; Cohort 2: Tamoxifen for 5 years

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cohort 1 (premenopausal women at diagnosis converted to postmenopausal)
• Women who were pre- or perimenopausal at diagnosis
• Luminal breast cancer (defined as estrogen-receptor positive \>/=10%, HER2-negative disease).
• Treated with tamoxifen for at least 80% of a 5-year period (+/- 6 months from treatment completion).
• No clinical signs of metastasis after 5 years tamoxifen treatment.
• cN+ breast cancer at diagnosis indicating the need for extended adjuvant endocrine therapy.
• Postmenopausal status at study entry defined according to the National Comprehensive Cancer Network Guidelines.
• Cohort 2 (postmenopausal women at breast cancer diagnosis)
• Women who were postmenopausal at diagnosis.
• Luminal breast cancer (defined as estrogen-receptor positive \>/=10%, HER2-negative disease).
• Treated with AI for at least 80% of a 5-year period (+/- 6 months from treatment completion).
• No clinical signs of metastasis after 5 years AI treatment.
• cN+ breast cancer at diagnosis indicating the need for extended adjuvant endocrine therapy.

You may not qualify if:

• Cohort 1
• Prior invasive breast cancer diagnosis.
• Other invasive malignancy within 5 years before or after breast cancer diagnosis
• Non-luminal breast cancer (defined as estrogen-receptor \< 10%).
• Patients who were unable to complete at least 80% of 5-year initial treatment with tamoxifen.
• Uncertain menopausal status (unable to evaluate menopausal status according to aforementioned definitions).
• Recurrent or metastatic breast cancer within or after 5-year initial treatment with tamoxifen (DCIS-only is allowed at any time before or after breast cancer diagnosis).
• \) Unable to give informed consent in Swedish. Cohort 2
• Prior invasive breast cancer diagnosis.
• Other invasive malignancy within 5 years before or after breast cancer diagnosis; non-Luminal breast cancer (defined as estrogen-receptor \< 10%).
• Patients who were unable to complete at least 80% of 5-year initial treatment with AI.
• Recurrent or metastatic breast cancer within or after 5-year initial treatment with AI (DCIS-only is allowed at any time before or after breast cancer diagnosis).
• \) No contraindication for tamoxifen therapy. 7) Unable to give informed consent in Swedish.

Sponsors & Collaborators

• Region Örebro County: lead
• Mid-Sweden Regional Cancer Centre: collaborator
• Akademiska University Hospital, Uppsala, Sweden: collaborator

Study Sites (15)

Visby Hospital

Visby, Gotland County, Sweden

Location

General Hospital of Eskilstuna

Eskilstuna, Sweden

Location

Falun County Hospital

Falun, Sweden

Location

Gävle Hospital

Gävle, Sweden

Location

Sahlgrenska University Hospital

Gothenburg, Sweden

Location

Ryhov County Hospital

Jönköping, Sweden

Location

Kalmar Hospital

Kalmar, Sweden

Location

Lund University Hospital

Lund, Sweden

Location

Örebro University Hospital

Örebro, Sweden

Location

Karolinska University Hospital

Stockholm, Sweden

Location

St Göran Capio Hospital

Stockholm, Sweden

Location

University Hospital of Umeå

Umeå, Sweden

Location

Akademiska University Hospital Uppsala

Uppsala, Sweden

Location

Växjö Hospital

Vaxjo, Sweden

Location

Västerås General Hospital

Västerås, Sweden

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Letrozole; Anastrozole; exemestane; Tamoxifen

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Central Study Contacts

Antonis Valachis, MD, PhD

CONTACT

0046 196021000; antonios.valachis@oru.se

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two separate cohorts will be randomized (two arms in each study cohort)

Study Record Dates

• First Submitted: December 29, 2023
• First Posted: January 25, 2024
• Study Start: May 2, 2025
• Primary Completion (Estimated): May 2, 2032
• Study Completion (Estimated): May 2, 2035
• Last Updated: April 20, 2025

Record last verified: 2025-01

Locations

SE (15)