An expanded access study for postmenopausal women with estrogen receptor positive locally advanced or metastatic breast cancer who have progressed following prior endocrine therapy, investigating the treatment of everolimus (RAD001) in combination with exemestane

• Register: EUCTR
• Last refreshed on: 14 September 2015
• Main ID: EUCTR2012-000073-23-IT
• Date of registration: 31/08/2012
• Prospective Registration: No
• Primary sponsor: NOVARTIS FARMA
• Public title: An expanded access study for postmenopausal women with estrogen receptor positive locally advanced or metastatic breast cancer who have progressed following prior endocrine therapy, investigating the treatment of everolimus (RAD001) in combination with exemestane
• Scientific title: An open-label, multi-center, expanded access study for postmenopausal women with estrogen receptor positive locally advanced or metastatic breast cancer who have progressed following prior endocrine therapy, investigating the treatment of everolimus (RAD001) in combination with exemestane
• Date of first enrolment: 08/05/2012
• Target sample size: 2200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000073-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: Placebo: Other: Number of treatment arms in the trial: 1

Countries of recruitment

Austria, Belgium, Bulgaria, Denmark, Finland, Hungary, Ireland, Italy, Netherlands, Norway, Slovakia, Spain, Sweden

Contacts

• Name: Drug Regulatory Affairs
• Affiliation: NOVARTIS FARMA

• Name: Drug Regulatory Affairs
• Affiliation: NOVARTIS FARMA

Key inclusion & exclusion criteria

Inclusion criteria:
1. Adult women (= 18 years of age) with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy. 2. Histological or cytological confirmation of estrogen-receptor positive (ER+) breast cancer. 3. Postmenopausal women. Postmenopausal status is defined either by: • Age = 55 years and one year or more of amenorrhea • Age < 55 years and one year or more of amenorrhea, with an estradiol assay < 20 pg/ml • Surgical menopause with bilateral oophorectomy. Note: Ovarian radiation or treatment with a luteinizing hormone-releasing hormone (LH-RH) agonist (goserelin acetate or leuprolide acetate) is not permitted for induction of ovarian suppression. 4. Disease refractory to NSAI, defined as: a. Recurrence while on or within 12 months of end of adjuvant treatment with letrozole or anastrozole, or b. Progression while on or within one month of end of letrozole or anastrozole treatment for advanced BC ( locally advanced or metastatic ) • Note: Letrozole or anastrozole do not have to be the last treatment prior to enrollment. Other prior anticancer therapy, e.g. tamoxifen, fulvestrant are allowed. Patients must have recovered to grade 1 or better from any adverse events (except alopecia) related to previous therapy prior to enrollment. • Radiological or clinical evidence of recurrence or progression on last systemic therapy prior to enrollment. Note: There are no restrictions as to the last systemic therapy prior to enrollment. 5. Adequate bone marrow and coagulation function as shown by: • Absolute neutrophil count (ANC) = 1.5 109/L • Platelets = 100 ×109/L •emoglobin (Hgb) = 9.0 g/dL • INR = 2 6. Adequate liver function as shown by: • Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 ULN (or = 5 if hepatic metastases are present) • Total serum bilirubin = 1.5 × ULN (= 3 × ULN for patients known to have Gilbert Syndrome) 7. Adequate renal function as shown by: • Serum creatinine = 1.5 × ULN 8. Fasting serum cholesterol = 300 mg/dl or 7.75 mmol/L and fasting triglycerides = 2.5 × ULN. In case one or both of these thresholds are exceeded, the patient can only be included after initiation of statin therapy or other lipid lowering drugs (eg fibrates), and when the above mentioned values have been achieved 9. Written informed consent obtained before any screening procedure and according to local guidelines.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 500
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1700

Exclusion criteria:
1. HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive). 2. Previous treatment with exemestane or mTOR inhibitors. Except for the treatment with exemestane in the adjuvant setting providing patient remained disease-free for at least one year following completion. 3. Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin). 4. Radiotherapy within four weeks prior to enrollment except in case of localized radiotherapy for analgesic purpose or for lytic lesions at risk of fracture which can then be completed within two weeks prior to enrollment. Patients must have recovered from radiotherapy toxicities prior to enrollment. 5. Currently receiving hormone replacement therapy, unless discontinued prior to enrollment. 6. Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use, at the time of study entry except in cases outlined below: Topical applications (e.g. rash), inhaled sprays (e.g. obstructive airways diseases), eye drops or local injections (e.g. intra-articular) are allowed. Patients on stable low dose of corticosteroids for at least two weeks before enrollment are allowed in case of treatment of brain metastases. 7. Bilateral diffuse lymphangitic carcinomatosis or metastasis of the lung as the only manifestation of disease (>50% of lung involvement), evidence of metastases estimated as more than a third of the liver as defined by sonogram and/or CT scan. 8. Patients with a known history of HIV seropositivity. 9. Active, bleeding diathesis, or on oral anti-vitamin K medication (except low dose warfarin and acetylsalicylic acid or equivalent, as long as the INR is = 2.0) 10. Any severe and / or uncontrolled medical conditions such as: • Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =6 months prior to enrollment, serious uncontrolled cardiac arrhythmia • Uncontrolled diabetes as defined by fasting serum glucose > 1.5 × ULN • Acute and chronic, active infectious disorders and nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this study therapy • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome) • Significant symptomatic deterioration of lung function. If clinically indicated, pulmonary function tests including measures of predicted lung volumes, DLco, O2 saturation at rest on room air should be considered to exclude restrictive pulmonary disease, pneumonitis or pulmonary infiltrates. 11. Patients who test positive for hepatitis B or C (Patients who test negative for HBV-DNA, HBsAg, and HBcAb but positive for HBsAb with prior history of vaccination against Hepatitis B will be eligible) 12. Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A (Rifabutin, Rifampicin, Clarithromycin, Ketoconazole, Itroconazole, Voriconazole, Ritinavir, Telithromycin) within the last 5 days prior to enrollment 13. History of non-compliance to medical regimens 14. Patients unwilling to or unable to comply with the protocol


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Estrogen receptor positive locally advanced or metastatic breast cancer in postmenopausal women
MedDRA version: 15.0 Level: PT Classification code 10006187 Term: Breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: AFINITOR*30CPR 5MG
Pharmaceutical Form: Tablet
INN or Proposed INN: EVEROLIMUS
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Trade Name: AFINITOR*30CPR 10MG
Pharmaceutical Form: Tablet
INN or Proposed INN: EVEROLIMUS
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Trade Name: AROMASIN*30CPR RIV 25MG
Pharmaceutical Form: Coated tablet
INN or Proposed INN: EXEMESTANE
CAS Number: 107868-30-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Primary Outcome(s)

Secondary Objective: - to evaluate adverse events grade 3 and 4 in the routine practice - to explore the tolerability of the concomitant treatment of zoledronic acid RTU (Ready To Use) formulation in patients who will receive this treatment according to the clinical practice

Main Objective: To evaluate safety of everolimus (RAD001) in postmenopausal women with estrogen receptor positive locally advanced or metastatic breast cancer that is refractory to NSAIs

Primary end point(s): frequency of adverse events and number of laboratory values that are new or worsening

Timepoint(s) of evaluation of this end point: Adverse events: continuously, up to 28 days after last treatment Laboratory values: continuously or as frequently as clinically indicated

Secondary Outcome(s)

Secondary end point(s): - frequency of adverse events that is recorded as Grade 3 or 4 or as Serious Adverse Event - frequency of adverse events of any grade in the group of patients who have received concomitant treatment with zoledronic acid RTU formulation, administered according to clinical practice

Timepoint(s) of evaluation of this end point: Continuously, up to 28 days after the last treatment

Secondary ID(s)

CRAD001YIC04

2012-000073-23-AT

Source(s) of Monetary Support

Novartis Pharma Services AG