Overview

This trial is active, not recruiting.

Condition breast neoplasms
Treatments letrozole, afatinib
Phase phase 2
Targets HER2, EGFR, HER, HER4
Sponsor Translational Research in Oncology
Collaborator Boehringer Ingelheim
Start date July 2014
End date March 2017
Trial size 44 participants
Trial identifier NCT02115048, TRIO 020

Summary

The purpose of the study is to compare the efficacy of treatment with afatinib plus letrozole to treatment with letrozole alone in women diagnosed with a specific type of breast cancer.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
Continuous regimen of oral Letrozole 2.5 mg daily
letrozole
(Experimental)
Continuous regimen of oral Letrozole 2.5 mg daily plus oral Afatinib 30 mg daily
letrozole
afatinib

Primary Outcomes

Measure
Progression Free Survival
time frame: Every 12 weeks up to 9 months (average) for subjects in the control arm or up to 14 months (average) for subjects in the experimental arm

Secondary Outcomes

Measure
Overall Survival (OS)
time frame: Under treatment: every 4 wks up to 9 months (average) for subject in the control arm or up to 14 months (average) for subjects in the experimental arm. After documentation of disease progression up to the end of the study: every 6 months up to 42 months
Objective Response Rate (OR)
time frame: Every 12 weeks up to 9 months (average) for subjects in the control arm or up to 14 months (average) for subjects in the experimental arm
Time to tumor progression (TTP)
time frame: Every 12 weeks up to 9 months (average) for subjects in the control arm or up to 14 months (average) for subjects in the experimental arm
Incidence of Adverse Events
time frame: Under treatment: every 4 wks up to 9 months (average) for subjects in the control arm or up to 14 months (average) for subjects in the experimental arm. After documentation of disease progression up to the end of the study: every 6 months up to 42 months
Laboratory Parameters
time frame: every 4 weeks up to 9 months (average) for subjects in the control arm or up to 14 months (average) for subjects in the experimental arm
ECOG Performance Status
time frame: Every 4 weeks up to 9 months (average) for subjects in the control arm or up to 14 months (average) for subjects in the experimental arm
Left Ventricular Ejection Fraction (LVEF)
time frame: Every 12 weeks up to 9 months (average) for subjects in the control arm or up to 14 months (average) for subjects in the experimental arm

Eligibility Criteria

Female participants at least 18 years old.

Inclusion Criteria: - Signed and dated informed consent. - Postmenopausal females, 18 years of age or older. - Histologically or cytologically proven diagnosis of adenocarcinoma of the breast with evidence of locally recurrent disease not amenable to resection or radiation therapy with curative intent, or metastatic disease. - HER2 negative breast cancer. Central testing (required for all subjects) must demonstrate that the tumor is HER2 negative by FISH or Immunohistochemistry (IHC). - ER positive breast cancer. Central testing (required for all subjects) must demonstrate that the tumor is ER+ with low expression (H-score [1-159]). - Paraffin-embedded tumor block(s) or 15 to 20 unstained slides available for centralized assessment of ER, PR, and HER2. - Measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 or bone-only non measurable disease. - Eastern Cooperative Oncology Group (ECOG) Performance status 0 or 1. - Adequate hematological, hepatic and renal functions. - Baseline left ventricular ejection fraction (LVEF) 50%. - Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures. Exclusion Criteria: - Brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease. - Prior treatment with any type of systemic therapy for advanced disease. - Prior treatment with letrozole in (neo)adjuvant setting with disease-free interval ≤ 12 months from completion of treatment until randomization. - Prior treatment with any anti HER-family targeted therapy in (neo)adjuvant setting. - Any concurrent or previous malignancy within 5 years prior to randomization, except for adequately and radically treated basal or squamous skin cancer, or carcinoma in situ of the cervix, or other non-invasive/in-situ neoplasm. - Non-measurable disease according to RECIST 1.1, with the exception of bone-only non-measurable disease. - Known pre-existing interstitial lung disease. - Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom. - History or presence of clinically relevant cardiovascular abnormalities as per investigator assessment. - Any other concomitant serious illness or organ system dysfunction as per investigator assessment - Any contraindication to oral agents. - Active hepatitis B infection, active hepatitis C infection or known HIV carrier. - Known or suspected active drug or alcohol abuse. - Known hypersensitivity to afatinib or letrozole or the excipients of any of the trial drugs. - Concomitant treatment with strong inhibitor of P-gp. - Any ongoing acute clinically significant toxic effect of prior anticancer therapy or any persisting complication of prior surgery. - Subjects with known history of keratitis, ulcerative keratitis or severe dry eye. - Participation in the active phase of other clinical trials of investigational agents in which last study treatment was administered within 2 weeks prior to randomization

Additional Information

Official title A Randomized Open-label Phase II Study of Letrozole Plus Afatinib (BIBW2992) Versus Letrozole Alone in First Line Treatment of Advanced ER+, HER2- Post-menopausal Breast Cancer With Low ER Expression
Description This is an open-label, multicenter, international, randomized, Phase II clinical trial that will assess the efficacy and safety of letrozole in combination with afatinib(oral epidermal growth factor receptor (EGFR ) inhibitor) versus letrozole monotherapy for the first-line treatment of postmenopausal women with ER+, Human Epidermal Growth Factor Receptor 2 (HER2) negative advanced breast cancer with low ER expression. In order to assess the level of estrogen receptor (ER) expression we will use a semi-quantitative scoring system (McClelland, 1990) defined as : H-score = (% of cells stained at intensity category 1x1) + (% of cells stained at intensity category 2x2) + (% of cells stained at intensity category 3x3). This formula results in an H-score in the range of 0-300 where 300 equals 100% of tumor cells stained strongly (i.e., 3+). Low ER expression will be defined as tumor sample with H-score below 160 (Finn, 2009). All subjects who consented for the study must submit a tumor sample to the designated central laboratory for central confirmation of ER / Progesterone receptor (PR) and HER2 statuses and determination of the H-score. This will be assessed prior to randomization. Subjects with HER2 negative, ER+ advanced breast cancer with low ER expression defined as H-score between 1 and 159 will enter screening phase and perform the required screening assessments. Eligible subjects will be randomly assigned in a 1:1 ratio and stratified according to sites of disease (bone only disease vs. other) and prior administration of hormonal therapy in neo/adjuvant setting (Yes vs. No) to either: Arm A : Continuous regimen of oral letrozole 2.5 mg until progression of disease or any other study treatment discontinuation criteria. or Arm B : Continuous regimen of oral letrozole 2.5 mg daily plus oral afatinib 30 mg daily until progression of disease or any other study treatment discontinuation criteria. Once the subject is discontinued from study treatment and has undergone the End of Treatment visit, the subject will enter in the follow-up phase. A total of 150 subjects, 75 per arm, will be randomized over an estimated period of 18 months.
Trial information was received from ClinicalTrials.gov and was last updated in March 2016.
Information provided to ClinicalTrials.gov by Translational Research in Oncology.
Location data was received from the National Cancer Institute and was last updated in March 2016.