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

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ClinicalTrials.gov Identifier: NCT02115048
Recruitment Status : Terminated (Study was completed as per amended protocol. Protocol was amended to close enrollment earlier than initially planned (study continued as per plan).)
First Posted : April 15, 2014
Results First Posted : December 26, 2019
Last Update Posted : December 26, 2019
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by (Responsible Party):
Translational Research in Oncology

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.

Condition or disease Intervention/treatment Phase
Breast Neoplasms Drug: Letrozole Drug: Afatinib Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Open-label Phase II Study of Letrozole Plus Afatinib Versus Letrozole Alone in First-line Treatment of Advanced ER+, HER2- Postmenopausal Breast Cancer With Low ER Expression
Study Start Date : July 2014
Actual Primary Completion Date : November 2018
Actual Study Completion Date : November 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
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



Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: 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. ]

    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.



Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: 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 ]

    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


  2. Objective Response Rate (ORR) [ Time Frame: 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. ]

    Objective response rate (ORR) is defined as the proportion of randomized subjects achieving a best overall response of complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST). As per RECIST (version 1.1):

    CR is defined as disappearance of all target and non target lesions - lymph node (LN) <10mm.

    PR is defined as at least a 30% decrease in the Sum of Diameters, taking as reference the Baseline Sum of Diameters


  3. Time to Tumor Progression (TTP) [ Time Frame: 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. ]
    As per Response Evaluation Criteria In Solid Tumors (RECIST). Time to progression (TTP) is defined as the time interval from date of randomization to date of the first documented objective tumor progression.

  4. Number of Participants With Adverse Events [ Time Frame: 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 ]

    Participants who experienced at least one Treatment Emergent Adverse Event (TEAE) are presented. Participants with at least one serious TEAE, those who had at least one TEAE related to letrozole or afatinib (serious/non-serious), including participants who experienced a grade 3/4 TEAE, or who discontinued/died as a result of their TEAE are listed by treatment arm. Adverse events were tabulated by system organ class, preferred term and toxicity grade by treatment arm. For subjects in which treatment was discontinued for reasons different than progression of disease, the assessment was conducted every 12 weeks following treatment, and up to documentation of disease progression.

    ** Enrollment was closed prematurely due to low recruitment (only 44 participants enrolled) compared to what was initially planned (150 participants), therefore no statistical evaluations were completed. Adverse event data collected are described per arm but no statistical comparison was made.




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02115048


Locations
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Sponsors and Collaborators
Translational Research in Oncology
Boehringer Ingelheim
Investigators
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Study Chair: Richard Finn, MD University of California, Los Angeles
  Study Documents (Full-Text)

Documents provided by Translational Research in Oncology:
Study Protocol  [PDF] July 31, 2018
Statistical Analysis Plan  [PDF] December 4, 2014

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Responsible Party: Translational Research in Oncology
ClinicalTrials.gov Identifier: NCT02115048    
Other Study ID Numbers: TRIO 020
First Posted: April 15, 2014    Key Record Dates
Results First Posted: December 26, 2019
Last Update Posted: December 26, 2019
Last Verified: December 2019
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Afatinib
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Protein Kinase Inhibitors