Advance Breast cancer under endocrine treatment MedDRA version: 21.1 Level: LLT Classification code 10072737 Term: Advanced breast cancer System Organ Class: 100000004864 MedDRA version: 21.1 Level: LLT Classification code 10072740 Term: Locally advanced breast cancer System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Afinitor
Product Name: Afinitor
Product Code: RAD001
Pharmaceutical Form: Tablet
INN or Proposed INN: EVEROLIMUS
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Concentration unit: mg
Sponsors
GBG Forschungs GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Locally advanced or metastatic stage of disease not amenable to curative treatment by surgery or radiotherapy alone. - No indication for chemotherapy (e.g. symptomatic visceral metastasis) -Histological confirmed hormone receptor-positive (HR+), HER2-negative carcinoma of the breast. - Postmenopausal women - Disease progression following prior therapy with non steroidal aromatase inhibitors (NSAI), defined as: a. Recurrence while on, or following completion of an adjuvant treatment with Letrozole or Anastrozole, or b. Progression while on or following completion of Letrozole or Anastrozole treatment for ABC/MBC. Note: Non-steroidal aromatase inhibitors (i.e. Letrozole or Anastrozole) do not have to be the last treatment prior to enrollment. Other prior anticancer therapy, e.g. Tamoxifen, Fulvestrant, Exemestane, is also allowed. Patients must have recovered to grade 1 or better from any adverse events (except alopecia) related to previous therapy prior to enrollment. - At least 4 weeks since radiotherapy, with full recovery. The measurable disease must be completely outside the radiation field or there must be pathologic proof of newly progressive disease. 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 156 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 156
Exclusion criteria
Exclusion criteria: - Concurrent immunotherapy or hormonal therapy (contraceptive and/or replacement therapy). Bisphosphonates or denosumab may be continued or started before randomization. - Life expectancy of less than 3 months. - Parenchymal brain metastases, unless adequately controlled by surgery and/or radiotherapy. -Any ongoing toxicity from prior anti-cancer therapy that is grade 3-4 and/or that is progressing in severity, except alopecia or anemia controlled by growth factors. -Known or suspected congestive heart failure (>NYHA I) and/or coronary heart disease, angina pectoris requiring anti-anginal medication, previous history of myocardial infarction = 6months, evidence of transmural infarction on ECG, un- or poorly controlled arterial hypertension (i.e. BP >150/100 mmHg under treatment with two antihypertensive drugs), rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease. - Currently active infection. -History of other malignancies within the last 5 years which significantly affect the diagnosis, assessment or prognosis of metastatic breast cancer. -Malabsorption syndrome or insufficient gastrointestinal function, preexisting diagnosis of ulcerative colitis. -Concurrent treatment with other experimental drugs; participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry. -Insufficiently controlled diabetes, known HIV infection or chronic hepatitis B or C and seriously impaired liver function (Child-Pugh, class A, B or C).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the cumulative rate of mucositis/stomatitis grade 2-4 (WHO’s oral toxicity scale (OTS)) at 12 weeks after start of treatment using a conventional and a dose-escalating schema of everolimus in combination with exemestane in patients with metastatic breast cancer and progression or relapse after non-steroidal aromatase-inhibitor treatment.;Secondary Objective: • To compare the rate of patients on 10mg daily at 12 weeks and 24 weeks after start of everolimus treatment • To compare the clinical benefit rate (CR, PR und SD >=16 Weeks) at 24 weeks after start of everolimus treatment • To compare the safety with regard to other organ signs and symptoms • To compare the time to grade =2 mucositis/stomatitis • To compare the cumulative dose at 4 weeks • To compare the relative dose intensity for everolimus • To compare quality of life using the FACT-B questionnaire and the QSDQ • Potential biomarkers predicting safety and compliance will be determined after completion of study treatment;Primary end point(s): First episode of mucositis WHO’s OTS 2-4 ;Timepoint(s) of evaluation of this end point: any time during a 12 week period after start of everolimus | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Average dose of treatment during week 12 and during week 24. Clinical benefit rate (CBR) is defined as all patients with no evidence for tumor progression at 24 weeks after start of everolimus treatment. Safety by toxicity grades in general is defined by the NCI-CTCAE version 4.03, mucositis by WHO’s OTS. Cumulative dose will be calculated by adding all daily doses of everolimus until end of treatment or discontinuation. Relative dose intensity for everolimus is the ratio of Actual Total Dose Intensity (ATDI) and Planned Total Dose Intensity (PTDI), expressed as a percentage. Quality of life will be assessed using the FACT-B questionnaire and the QSDQ.;Timepoint(s) of evaluation of this end point: week 12 and week 24 | — |
Countries
Germany
Contacts
Public ContactClinical Trials Information Desiree
GBG Forschungs GmbH
Outcome results
None listed