An unblinded clinical trial for the treatment of a particular subtype of postmenopausal breast cancer where the patient will receive at random either Afatinib plus Letrozole or Letrozole alone

Phase 1

• Conditions: Advanced ER+, HER2- postmenopausal breast cancer with low ER expression; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-002192-18-ES
• Lead Sponsor: Translational Research In Oncology

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-09-26
• Last Update Posted: 7 January 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 150

Inclusion Criteria

1.Signed and dated informed consent document indicating that the subject (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrollment.
2.Postmenopausal female, 18 years of age or older.
Postmenopausal status defined as:
oPrior bilateral surgical oophorectomy or
oAmenorrhea and age ? 60 years or
oAge < 60 years and amenorrhea for 12 or more months and FSH and estradiol in the postmenopausal ranges
3.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.
4.HER2 negative breast cancer. Local testing should demonstrate that the tumor is 0 or 1+ by immunohistochemistry (IHC) or is considered to be HER2 negative for gene amplification by fluorescence in-situ hybridization (FISH), chromogenic in-situ hybridization (CISH) or other in-situ hybridization (ISH) method. Central testing (required for all subjects) must demonstrate that the tumor is HER2 negative by FISH or IHC.
5.ER positive breast cancer. Local testing should demonstrate that the tumor is ER positive. Central testing (required for all subjects) must demonstrate that the tumor is ER+, low amplification (H-score < 160).
6.Paraffin-embedded tumor block(s) available for centralized assessment of ER, PR, and HER2. If no tumor block is available, 15 to 20 unstained slides of paraffin-embedded tissue from the tumor obtained at the initial diagnosis or prior biopsy or surgery (archived tumor tissue) will be accepted. Slides must be positively charged, frosted-end. Tumor biopsies may be from either the primary or metastatic site of disease.
When tumor tissue from the primary tumor and from metastatic sites is available, the sample from the most recent biopsy/surgery/procedure will be sent to Central laboratory.
7.Measurable disease according to RECIST 1.1 (E.A. Eisenhauer 2009) or bone-only non measurable disease according to RECIST 1.1. Previously irradiated lesions are deemed measurable only if progression is documented at the site after completion of radiation.
8.Eastern Cooperative Oncology Group (ECOG) Performance status 0 or 1.
9.Adequate organ function as defined by the following criteria:
-Hemoglobin ? 9 g/dL
-Absolute neutrophils count (ANC) ? 1.2 x 109/L
-Platelets ? 100 x 109/L
-Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ? 3 x upper limit of normal (ULN), or AST and ALT ? 5 x ULN if liver function abnormalities are due to liver metastasis.
-Total serum Bilirubin ? 1.5 mg/dL (? 26 µ mol/L) regardless of liver involvement secondary to tumor. Inclusion of subjects with increased serum indirect bilirubin due to Gilbert?s syndrome is permitted.
-Serum creatinine ? 1.5 x ULN. For subjects with serum creatinine > 1.5 x ULN then calculated (Cockcroft-Gault formula) or measured Creatinine clearance ? 60 mL/min is required.
10.Baseline resting left ventricular ejection fraction (LVEF) ? 50% measured by multigated acquisition scan (MUGA scan) or echocardiogram.
11.Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 75
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 75

Exclusion Criteria

1.Brain metastases (even if treated and/or stable), spinal cord compression, carcinomatous meningitis, or leptomeningeal disease.
2.Prior treatment with any type of systemic therapy for locally-recurrent disease not amenable to resection or radiation therapy with curative intent, or for metastatic disease.
3.Prior treatment with letrozole in (neo)adjuvant setting with disease-free interval ? 12 months from completion of treatment until randomization.
4.Prior treatment with any anti HER-family targeted therapy in (neo)adjuvant setting.
5.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. A subject with previous history of invasive malignancy (other than adequately and radically treated basal or squamous skin cancer) is eligible provided that she has been disease free for more than 5 years.
6.Non-measurable disease according to RECIST 1.1 (E.A. Eisenhauer 2009), with the exception of bone-only non-measurable disease.
7.Known pre-existing interstitial lung disease.
8.Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom e.g. Crohn's disease, malabsorption or CTCAE v4.0 grade ? 2 diarrhea of any aetiology.
9.History or presence of clinically relevant cardiovascular abnormalities, as per investigator assessment such as uncontrolled hypertension, congestive heart failure NYHA Class ? III, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to randomization.
10.Any other concomitant serious illness or organ system dysfunction which in the opinion of the investigator would either compromise subject safety or interfere with the evaluation of the safety of the test drug.
11.Any contraindication to oral agents.
12.Active hepatitis B infection (defined as presence of Hep B sAg and/or Hep B DNA), active hepatitis C infection (defined as presence of Hep C RNA) or known HIV carrier.
13.Known or suspected active drug or alcohol abuse.
14.Known hypersensitivity to afatinib or letrozole or the excipients of any of the trial drugs.
15.Concomitant treatment with strong inhibitor of P-gp.
16.Any ongoing acute clinically significant toxic effect of prior anticancer therapy or any persisting complication of prior surgery.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified