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

NCT02115048 | Terminated Phase 2 Results DMC

• 1 other identifier: TRIO 020
• Study Type: interventional
• Target: 44
• Locations: 4 countries
• Sites: 26

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.

Conditions

Breast Neoplasms

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Progression Free Survival (PFS) is defined as the time from randomization until date of progression (assessed by Response Evaluation Criteria in Solid Tumors - RECIST) or death due to any cause, whichever occurs first. For evaluation of PFS, the randomization date for each patient was the "start date". If the status at the last assessment date was "Non-complete response/ Non-progressive disease" or "Complete response", then the patient was considered "censored". If the status at the last assessment for any tumor was "Progressive disease", then the patient was considered as having an event. Progressive disease is defined using RECIST v1 .1 as a ≥ 20% increase in the sum of the longest diameter of target lesions compared with the smallest-sum longest diameter recorded or the appearance of one or more target or non-target new lesions and/or unequivocal progression of existing non-target lesions.

  Tumor assessments were every 12 weeks up to 9 months (average) for subjects in Arm A or up to 14 months (average) for subjects in Arm B.

Secondary Outcomes (4)

• Overall Survival (OS)

  Under treatment: every 4 wks up to 9 months (average) for subject in the Arm A or up to 14 months (average) for subjects in Arm B. After documentation of disease progression up to the end of the study: every 6 months up to 42 months

• Objective Response Rate (ORR)

  Tumor assessment: every 12 weeks up to 9 months (average) for subjects in Arm A or up to 14 months (average) for subjects in Arm B.

• Time to Tumor Progression (TTP)

  Tumor assessments: every 12 weeks up to 9 months (average) for subjects in Arm A or up to 14 months (average) for subjects in Arm B.

• Number of Participants With Adverse Events

  Under treatment: every 4 wks up to 9 months (average) for subjects in Arm A or up to 14 months (average) for subjects in Arm B. After documentation of disease progression up to the end of the study: every 6 months up to 42 months

Study Arms (2)

Arm A

ACTIVE COMPARATOR

Continuous regimen of oral Letrozole 2.5 mg daily

Drug: Letrozole

Arm B

EXPERIMENTAL

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

Drug: Letrozole; Drug: Afatinib

Interventions

Letrozole DRUG

Arm A; Arm B

Afatinib DRUG

Arm B

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Translational Research in Oncology: lead
• Boehringer Ingelheim: collaborator

Study Sites (26)

St. Jude Heritage Healthcare

Fullerton, California, 92835, United States

Location

University of California Los Angeles Hematology Oncology

Los Angeles, California, 90095, United States

Location

West Valley Hematology Oncology Medical Group

Northridge, California, 91328, United States

Location

DBA Torrance Memorial Physician Network/Cancer Care Associates

Redondo Beach, California, 90277, United States

Location

Coastal Integrative Cancer Care

San Luis Obispo, California, 93401, United States

Location

Central Coast Medical Oncology Corporation

Santa Maria, California, 93454, United States

Location

Orlando Health, Inc.

Orlando, Florida, 32806, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

Hope Women's Cancer Centers

Asheville, North Carolina, 28806, United States

Location

University Hospital Clinical Center Banja Luka, Oncology Clinic

Banja Luka, 78000, Bosnia and Herzegovina

Location

Clinical Center of University in Sarajevo, Clinic for Oncology

Sarajevo, 71000, Bosnia and Herzegovina

Location

University Clinical Center Tuzla Clinic for Oncology, Hematology and Radiotherapy

Tuzla, 75000, Bosnia and Herzegovina

Location

Filantropia Clinical Hospital

Bucharest, Romania

Location

County Emergency Clinical Hospital Cluj-Napoca Oncology Department

Cluj-Napoca, 400006, Romania

Location

SC Medisprof SRL

Cluj-Napoca, 400058, Romania

Location

County Hospital Ploiesti

Ploieşti, 100337, Romania

Location

County Emergency Hospital "Sf Ioan cel Nou"

Suceava, 720237, Romania

Location

Oncomed SRL Timisoara

Timișoara, Romania

Location

Complexo Hospitalario Universitario A Coruña

A Coruña, 15006, Spain

Location

Complejo Hospitalario Universitario de Albacete

Albacete, 02006, Spain

Location

Hospital General Universitario de Alicante

Alicante, 03010, Spain

Location

Hospital de Especialidades de Jerez de La Frontera

Jerez de la Frontera, 11408, Spain

Location

Hospital Clínico Universitario Virgen de La Arrixaca

Murcia, 30120, Spain

Location

Hospital Son Llatzer

Palma de Mallorca, 07198, Spain

Location

Hospital Universitari de Sant Joan de Reus

Reus, 43204, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Letrozole; Afatinib

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; Amides; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Enrolment was closed prematurely with only 44 participants enrolled compared to what was initially planned (150 participants). Thus, preventing appropriate statistical evaluation (primary/secondary objectives no longer applicable as per protocol).

Results Point of Contact

• Title: Director, Project Management
• Organization: Translational Research In Oncology (TRIO)

TRIO020.contact@trioncology.org

+33 1 58 10 09 09

Study Officials

• Richard Finn, MD

  University of California, Los Angeles

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2014
• First Posted: April 15, 2014
• Study Start: July 1, 2014
• Primary Completion: November 1, 2018
• Study Completion: November 1, 2018
• Last Updated: December 26, 2019
• Results First Posted: December 26, 2019

Record last verified: 2019-12

Locations

US (9); RO (6); ES (8); BO (3)