Clinical Study for the Treatment of Breast Cancer: the Patient Will Receive Afatinib Plus Letrozole or Letrozole Alone

NCT ID: NCT02115048

Last Updated: 2019-12-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-31
• Study Completion Date: 2018-11-30

Brief 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.

Detailed 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.

IN ADDITION the following applies whichever comes first:

• If the patients treated with the combination of afatinib and letrozole (arm B) discontinue the trial treatment (whatever the reason) before 30 November 2018, the patients from the other arm (arm A, letrozole alone) still on treatment will also be discontinued from the trial at the same time. They may continue receiving letrozole using commercial drug as standard of care according to their treating physician discretion.
• If the patients treated with afatinib and letrozole (arm B) have not discontinued the trial treatment by 30 November 2018, all patients currently on treatment in the trial (including the ones only treated by letrozole alone (arm A)) will be discontinued from the trial at that time. They may continue receiving their treatment if in alignment with their treating physician judgment as follows:
• Patients in arm A: may continue receiving letrozole using commercial drug as standard of care according to their treating physician discretion.
• Patients in arm B: may continue receiving afatinib in the context of alternative drug supply outside the clinical trial as appropriate according to local legislation. Additionally, they may continue receiving letrozole using commercial drug as standard of care according to their treating physician discretion.

Once the patient is discontinued from trial treatment and has undergone the End of Treatment Visit, she will be permanently discontinued from the trial and treated as per local clinical practice.

Conditions

Breast Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A

Continuous regimen of oral Letrozole 2.5 mg daily

Group Type: ACTIVE_COMPARATOR

Letrozole

Intervention Type: DRUG

Arm B

Continuous regimen of oral Letrozole 2.5 mg daily plus oral Afatinib 30 mg daily

Group Type: EXPERIMENTAL

Letrozole

Intervention Type: DRUG

Afatinib

Intervention Type: DRUG

Interventions

Letrozole

Intervention Type: DRUG

Afatinib

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: collaborator

Translational Research in Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Richard Finn, MD

Role: STUDY_CHAIR

University of California, Los Angeles

Locations

St. Jude Heritage Healthcare

Fullerton, California, United States

University of California Los Angeles Hematology Oncology

Los Angeles, California, United States

West Valley Hematology Oncology Medical Group

Northridge, California, United States

DBA Torrance Memorial Physician Network/Cancer Care Associates

Redondo Beach, California, United States

Coastal Integrative Cancer Care

San Luis Obispo, California, United States

Central Coast Medical Oncology Corporation

Santa Maria, California, United States

Orlando Health, Inc.

Orlando, Florida, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Hope Women's Cancer Centers

Asheville, North Carolina, United States

University Hospital Clinical Center Banja Luka, Oncology Clinic

Banja Luka, , Bosnia and Herzegovina

Clinical Center of University in Sarajevo, Clinic for Oncology

Sarajevo, , Bosnia and Herzegovina

University Clinical Center Tuzla Clinic for Oncology, Hematology and Radiotherapy

Tuzla, , Bosnia and Herzegovina

Filantropia Clinical Hospital

Bucharest, , Romania

County Emergency Clinical Hospital Cluj-Napoca Oncology Department

Cluj-Napoca, , Romania

SC Medisprof SRL

Cluj-Napoca, , Romania

County Hospital Ploiesti

Ploieşti, , Romania

County Emergency Hospital "Sf Ioan cel Nou"

Suceava, , Romania

Oncomed SRL Timisoara

Timișoara, , Romania

Complexo Hospitalario Universitario A Coruña

A Coruña, , Spain

Complejo Hospitalario Universitario de Albacete

Albacete, , Spain

Hospital General Universitario de Alicante

Alicante, , Spain

Hospital de Especialidades de Jerez de La Frontera

Jerez de la Frontera, , Spain

Hospital Clínico Universitario Virgen de La Arrixaca

Murcia, , Spain

Hospital Son Llatzer

Palma de Mallorca, , Spain

Hospital Universitari de Sant Joan de Reus

Reus, , Spain

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Countries

United States; Bosnia and Herzegovina; Romania; Spain

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

TRIO 020

Identifier Type: -

Identifier Source: org_study_id