A pilot, phase II, unblinded, single-arm study to evaluate how biomarkers of hormonal resistance work against treatment with everolimus plus letrozol in first line treatment of postmenopausal women with hormone positive metastatic or locallyadvanced breast cancer

• Conditions: Estrogen receptor or progesterone receptor positive locally advanced or metastatic breast cancer in postmenopausal women; MedDRA version: 16.1Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-004139-62-ES
• Lead Sponsor: ovartis Farmacéutica S. A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-11-12
• Last Update Posted: 5 August 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: Not specified

Inclusion Criteria

1. Patient signed informed consent both for study and sample cession. Written informed consent must be obtained before any trial related activity and according to local guidelines.
2. Post-menopausal women (>18 years of age) with metastatic or locally advanced unresectable disease. The patients must be treatment-naïve for advanced disease, although any agent is permitted during the adjuvant/neoadjuvant treatment.
3. Disease relapses at any time, during or after adjuvant therapy
4. Histopathological confirmation of hormone-receptor positive (estrogen-receptor positive (ER+) or progesterone receptor positive (PR+), defined as positivity of 10% in either of the receptors) and human epidermal growth factor receptor 2 negative (HER2-) breast cancer.
5. Ductal or lobular breast cancer are allowed.
6. Available paraffin tumor sample at the time of diagnosis. Histologic confirmation of the disease site is also recommendable. In that case, if sufficient material is available after diagnosis, the sample should be sent to the sponsor.
7. Postmenopausal women. Postmenopausal status is defined either by:
a. Age >55 years and one year or more of amenorrhea
b. Age < 55 years and one year or more of amenorrhea, with an estradiol assay <20pg/ml
c. Surgical menopause with bilateral oophorectomy
d. Note: Ovarian radiation or treatment with a luteinizing hormone-release hormone (LHRH) agonist (goserelin acetate or leuprolide acetate) is not permitted for induction of ovarian suppression
8. No prior treatment for metastatic/advanced breast cancer.
9. Patients must either have at least one lesion that can be accurately measured in at least one dimension >20mm with conventional imaging techniques or >10mm with spiral CT or evaluable disease defined as bone lesions: lytic or mixed (lytic plus sclerotic) in the absence of measurable disease as defined above
10. Adequate bone marrow and coagulation function as shown by:
a. Absolute neutrophil count (ANC) >1.5x109/L
b. Platelets >100x109/L
c. Hemoglobin (Hgb) >9.0g/dL
d. INR <2
11. Adequate liver function as shown by:
a. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2.5xULN (or <5 if hepatic metastases are present)
b. Total serum bilirubin <1.5xULN (<3xULN for patients known to have Gilberts Syndrome)
12. Adequate renal function as shown by:
a. Serum creatinine < 1.5xULN
b. Creatinine clearance ?50 ml/minute
13. Fasting serum cholesterol <300 mg/dL or 7.75 mmol/L and fasting triglycerides <2.5 x ULN.
14. ECOG Performance Status <2
15. Life expectancy >3 months
16. Loco-regional treatment (radiation, surgery) of one or more sites is allowed, as long as there are more non-treated sites prior to initiation of study treatment.
17. Ability to take oral medication and to comply with the study 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 53
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 53

Exclusion Criteria

1. Patients with only non-measurable lesions other than bone metastasis as define above (e.g., pleural effusion, ascites, etc).
2. Patients who have received prior hormonal or any other systemic therapy for metastatic / advanced breast cancer.
3. HER-2 positive and triple-negative breast cancer. A first metastatic relapse event that is limited to a single site and has been treated with radical intention (surgery, radiation therapy, etc.) constitutes an exclusion criteria, including single-site brain metastasis.
4. Previous treatment with mTOR inhibitors.
5. Known hypersensitivity to mTOR inhibitors, e.g., sirolimus (rapamycin), everolimus or letrozole.
6. Neoadjuvant or adjuvant treatment termination due to intolerance to letrozole.
7. Lack of paraffin tumor sample from the initial breast cancer diagnosis. Patient is not eligible if only a post-neoadjuvant treatment sample is available.
8. Another malignancy within 5 years prior to enrollment with the exception of adequately treated in-situ carcinoma of the cervix uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer
9. Radiotherapy within four weeks prior to enrollment except in case of localized radiotherapy for analgesic purpose of lytic lesions at risk of fracture which can then be completed within two weeks prior to enrollment.
10. Currently receiving hormone replacement therapy, unless discontinued prior to enrollment
11. Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use, at the time of study entry except in cases outlined below: Prolonged systemic corticosteroid treatment during study, except for topical applications (e.g. rash),inhaled sprays (e.g. obstructive airways diseases), eye drops or local injections (e.g. intraarticular) should not be given. However, during the study:
? short duration (<2 weeks) of systemic corticosteroids is allowed (e.g. chronic obstructive pulmonary disease, anti-emetic);
? low doses of corticosteroids for brain metastasis treatment is allowed.
12. Bilateral diffuse lymphangitic carcinomatosis.
13. Patients with a known history of HIV seropositivity. Screening for HIV infection at baseline is not required.
14. Active bleeding diathesis.
15. Any severe and/or uncontrolled medical conditions such as:
a. Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction <6 months prior to enrollment, serious uncontrolled cardiac arrhythmia.
b. Uncontrolled diabetes as defined by fasting serum glucose >1.5xULN.
c. Impairment of gastrointestinal function or who have gastrointestinal disease that may significantly alter the absorption of study drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome)
d. Active skin, mucosa, ocular or GI disorders of Grade >1
e. Uncontrolled Chronic Obstructive Pulmonary Disease
f. Severe mental impairment
g. Seizure
h. Acute and chronic, active infectious disorders (except for Hep B and Hep C positive patients) and nonmalignant medical illness that are uncontrolled or whose control may be jeopardized by the complications of this study therapy
i. Any other severe condition that according to the investigator could interfere with the administration of the study treatment.
16. Patients who have undergone major surgery within 4 weeks prior to starting study drug (e.g., intra-thoracic, intra-abdominal, or intra-pelvic).
17. Significant symptomatic deterioration of lung function. If clinically indicated, pulmonary fu

Study & Design

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