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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2015 by Translational Research in Oncology
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by (Responsible Party):
Translational Research in Oncology
ClinicalTrials.gov Identifier:
NCT02115048
First received: April 9, 2014
Last updated: May 19, 2015
Last verified: May 2015
  Purpose

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.


Condition Intervention Phase
Breast Neoplasms
Drug: Letrozole
Drug: Afatinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Translational Research in Oncology:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    Progression Free Survival is defined as the time from randomization until date of progression (assessed by RECIST) or death due to any cause, whichever occurs first.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

    Overall Survival is defined as the time from randomization until death to any cause.

    For subjects in which treatment is discontinued for reasons different than Progression Disease: after treatment and up to documentation of disease progression: Overall Survival is assessed every 12 weeks


  • 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 ] [ Designated as safety issue: No ]
    As per RECIST

  • 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 ] [ Designated as safety issue: No ]
    As per RECIST

  • 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 ] [ Designated as safety issue: Yes ]

    Subject's incidence of adverse events will be tabulated by system organ class, preferred term and toxicity grade by treatment arm. Adverse events leading to death or drug discontinuation, drug related and serious adverse events will also be summarized by treatment arm.

    For subjects in which treatment is discontinued for reasons different than Progression Disease, after treatment and up to documentation of disease progression, the assessment of incidence of adverse events will be assessed every 12 weeks.


  • 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 ] [ Designated as safety issue: Yes ]
    Laboratory parameters, graded according to the NCI CTCAE v4.0, will be summarized at baseline, along visits and at the end of study treatment by treatment arm. Tables of shifts in toxicity will also be provided.

  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 150
Study Start Date: July 2014
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A
Continuous regimen of oral Letrozole 2.5 mg daily
Drug: Letrozole
Experimental: Arm B
Continuous regimen of oral Letrozole 2.5 mg daily plus oral Afatinib 30 mg daily
Drug: Letrozole Drug: Afatinib

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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02115048

Locations
United States, California
St. Jude Heritage Healthcare Recruiting
Fullerton, California, United States, 92835
Contact: Gayle Madden-Mathes, RN    714-446-5804    gmadden@mednet.ucla.edu   
Principal Investigator: William Eyre Lawler, MD         
University of California Los Angeles Hematology Oncology Recruiting
Los Angeles, California, United States, 90095
Contact: Monica Rocha, RN    310-825-7417    mprocha@mednet.ucla.edu   
Principal Investigator: Richard Finn, MD         
West Valley Hematology Oncology Medical Group Recruiting
Northridge, California, United States, 91328
Contact: Yacgley Valdes, SPAA/SRA    818-885-8500 ext 2832    yacgley.valdes@dignityhealth.org   
Principal Investigator: Sheldon J Davidson         
DBA Torrance Memorial Physician Network/Cancer Care Associates Recruiting
Redondo Beach, California, United States, 90277
Contact: Sherry Hutcherson, RN, CRC    310-750-3376    shutcherson@mednet.ucla.edu   
Principal Investigator: David Chan, MD         
Coastal Integrative Cancer Care Recruiting
San Luis Obispo, California, United States, 93401
Contact: Lee Alexandra Walton    805-543-5577    lwalton@ohmacc.com   
Principal Investigator: Brian A DiCarlo, MD         
Central Coast Medical Oncology Corporation Recruiting
Santa Maria, California, United States, 93454
Contact: Alison Fernandez, RN MPH OCN    805-346-3461    Alison.fernandez@dignityhealth.org   
Principal Investigator: Robert A Dichmann, MD         
United States, Florida
Orlando Health, Inc. Recruiting
Orlando, Florida, United States, 32806
Contact: Georgina Hollenbach, BSN, RN, OCN    321-841-1907    Georgina.Hollenbach@orlandohealth.com   
Principal Investigator: Rebecca Lynn Moroose, MD         
United States, Nevada
Comprehensive Cancer Centers of Nevada Recruiting
Las Vegas, Nevada, United States, 89169
Contact: Donna Katz, MSN, APRN, FNP-BC, OCN    702-952-3388    donnakatz@mednet.ucla.edu   
Principal Investigator: Heather Jeanne Allen, MD         
United States, North Carolina
Hope Women's Cancer Centers Recruiting
Asheville, North Carolina, United States, 28806
Contact: Laura Murphy, RN    828-670-8403      
Principal Investigator: Cameron Blaire Harkness, MD         
Bosnia and Herzegovina
University Hospital Clinical Center Banja Luka, Oncology Clinic Recruiting
Banja Luka, Bosnia and Herzegovina, 78000
Contact: Ivanka Rakita, Oncology Specialist    38751342678      
Principal Investigator: Ivanka Rakita, Oncology Specialist         
Clinical Center of University in Sarajevo, Clinic for Oncology Recruiting
Sarajevo, Bosnia and Herzegovina, 71000
Contact: Semir Beslija, Associate Professor    38733298356      
Principal Investigator: Semir Beslija, Associate Professor         
University Clinical Center Tuzla Clinic for Oncology, Hematology and Radiotherapy Recruiting
Tuzla, Bosnia and Herzegovina, 75000
Contact: Adnan Delibegovic, Oncology specialist    38735303363      
Principal Investigator: Adnan Delibegovic, Oncology Speicalist         
Romania
Filantropia Clinical Hospital Recruiting
Bucuresti, Romania
Contact: Dragos Median, senior Physician Oncology Spec    00402131830      
Principal Investigator: Dragos Median, senior Physician Oncology Spec         
County Emergency Clinical Hospital Cluj-Napoca Oncology Department Recruiting
Cluj Napoca, Romania, 400006
Contact: Larisa Ciule, Senior Physician Oncology Spec    40742025588      
Principal Investigator: Larisa Ciule, Senior Physician Oncology Spec         
SC Medisprof SRL Recruiting
Cluj Napoca, Romania, 400058
Contact: Anghel Adrian Udrea, Senior Physician Oncology Spec    0040264439270      
Principal Investigator: Anghel Adrian Udrea, Senior Physician Oncology Spec         
County Hospital Ploiesti Recruiting
Ploiesti, Romania, 100337
Contact: Gabriel Ghizdavescu, Senior Physician Oncology Spec    0040745176117      
Principal Investigator: Gabriel Ghizdavescu, Senior Physician Oncology Spec         
County Emergency Hospital "Sf Ioan cel Nou" Recruiting
Suceava, Romania, 720237
Contact: Doina Ganea Motan, Senior Physician Oncology Spec    0040722423653      
Principal Investigator: Doina Ganea Motan, Senior Physician Oncology Spec         
Oncomed SRL Timisoara Recruiting
Timisoara, Romania
Contact: Cristina Oprean, Senior Physician Oncology Spec    0040745148485      
Principal Investigator: Cristina Oprean, Senior Physician Oncology Spec         
Spain
Complejo Hospitalario Universitario de Albacete Recruiting
Albacete, Spain, 02006
Contact: Geicam       geicam@geicam.org   
Principal Investigator: Antonio Fernandez Aramburo, MD         
Hospital General Universitario de Alicante Recruiting
Alicante, Spain, 03010
Contact: Geicam       geicam@geicam.org   
Principal Investigator: José Juan Ponce Lorenzo, MD         
Complexo Hospitalario Universitario A Coruña Recruiting
Coruña, Spain, 15006
Contact: Geicam       geicam@geicam.org   
Principal Investigator: Silvia Antolin Novoa, MD         
Hospital de Especialidades de Jerez de La Frontera Recruiting
Jerez de la Frontera, Spain, 11408
Contact: Geicam       geicam@geicam.org   
Principal Investigator: Ruben De Toro Salas, MD         
Hospital Clínico Universitario Virgen de La Arrixaca Recruiting
Murcia, Spain, 30120
Contact: Geicam       geicam@geicam.org   
Principal Investigator: Jose Luis Alonso Romero, MD         
Hospital Son Llatzer Recruiting
Palma de Mallorca, Spain, 07198
Contact: Geicam       geicam@geicam.org   
Principal Investigator: Isabel Garau Llinas, MD         
Hospital Universitari de Sant Joan de Reus Recruiting
Reus, Spain, 43204
Contact: Geicam       geicam@geicam.org   
Principal Investigator: Isabel Ruiz, MD         
Hospital Universitario Miguel Servet Recruiting
Zaragoza, Spain, 50009
Contact: Geicam       geicam@geicam.org   
Principal Investigator: Antonio Anton Torres, MD         
Sponsors and Collaborators
Translational Research in Oncology
Boehringer Ingelheim
Investigators
Study Chair: Richard Finn, MD University of California, Los Angeles
  More Information

No publications provided

Responsible Party: Translational Research in Oncology
ClinicalTrials.gov Identifier: NCT02115048     History of Changes
Other Study ID Numbers: TRIO 020
Study First Received: April 9, 2014
Last Updated: May 19, 2015
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Bosnia: Federal Ministry of Health
Romania: National Agency for Medicines and Medical Devices
Romania: National Bioethics Committee of Medicines and Medical Devices
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Spain: Ethics Committee

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Letrozole
Antineoplastic Agents
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on July 30, 2015