Description:
The purpose of this study is to find out if combining everolimus with letrozole is safe and
has beneficial effects in postmenopausal women who have estrogen positive HER2 negative
locally advanced or metastatic breast cancer. Additionally, this study aims to find out if
everolimus plus exemestane is safe and has beneficial effects in women with estrogen positive
locally advanced or metastatic breast cancer after treatment with everolimus plus letrozole.
This study will also aim to find out if a mouth rinse can help reduce the severity of oral
stomatitis, a common side effect of everolimus. This part of the study will be conducted only
in countries where an alcohol free 0.5mg/5ml dexamethasone oral solution is commercially
available.
Title
- Brief Title: Open-label, Phase II, Study of Everolimus Plus Letrozole in Postmenopausal Women With ER+, HER2- Metastatic or Locally Advanced Breast Cancer
- Official Title: An Open-label, Phase II, Single-arm Study of Everolimus in Combination With Letrozole in the Treatment of Postmenopausal Women With Estrogen Receptor Positive HER2 Negative Metastatic or Locally Advanced Breast Cancer
Clinical Trial IDs
- ORG STUDY ID:
CRAD001Y24135
- SECONDARY ID:
2012-003065-17
- NCT ID:
NCT01698918
Conditions
- Hormone Receptor Positive Breast Cancer
Interventions
| Drug | Synonyms | Arms |
|---|
| Everolimus | RAD001 | Everolimus + letrozole/exemestane |
| Letrozole | Femara | Everolimus + letrozole/exemestane |
| Exemestane | Aromasin | Everolimus + letrozole/exemestane |
| Alcohol-free dexamethasone mouth rinse | alcohol-free dexamethasone 0.5 mg/5ml | Everolimus + letrozole/exemestane |
Purpose
The purpose of this study is to find out if combining everolimus with letrozole is safe and
has beneficial effects in postmenopausal women who have estrogen positive HER2 negative
locally advanced or metastatic breast cancer. Additionally, this study aims to find out if
everolimus plus exemestane is safe and has beneficial effects in women with estrogen positive
locally advanced or metastatic breast cancer after treatment with everolimus plus letrozole.
This study will also aim to find out if a mouth rinse can help reduce the severity of oral
stomatitis, a common side effect of everolimus. This part of the study will be conducted only
in countries where an alcohol free 0.5mg/5ml dexamethasone oral solution is commercially
available.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Everolimus + letrozole/exemestane | Experimental | Enrolled patients will receive everolimus in combination with letrozole in the first line setting until disease progression, unacceptable toxicity or withdrawal of consent. Following disease progression in the first line setting, patients will be offered everolimus in combination with exemestane. Patients who discontinue treatment in the first line setting due to unacceptable toxicity or due to withdrawal of consent will not be offered everolimus plus exemestane. Those patients treated in the second line setting will continue treatment until disease progression, unacceptable toxicity or withdrawal of consent. | - Everolimus
- Letrozole
- Exemestane
- Alcohol-free dexamethasone mouth rinse
|
Eligibility Criteria
Inclusion Criteria:
- Patients 18 years old or greater
- Patients with metastatic or locally advanced, unresectable breast cancer not amenable
to curative treatment by surgery or radiotherapy
- Histological or cytological confirmation of estrogen-receptor positive (ER+) human
epidermal growth factor receptor 2 negative (HER2-) breast cancer
- Postmenopausal women
- No prior treatment for metastatic breast cancer
Exclusion Criteria:
- Patients with only non-measurable lesions other than bone metastases (e.g., pleural
effusion, ascites, etc)
- Patients who have received prior hormonal or any other systemic therapy for metastatic
breast cancer.
- Patients may have received prior neoadjuvant or adjuvant endocrine therapy. In the
case of neoadjuvant or adjuvant NSAI (letrozole/anastrozole) therapy patients must
have completed therapy at least 1 year prior to study enrollment.
- Previous treatment with mTOR inhibitors.
- Known hypersensitivity to mTOR inhibitors, e.g., sirolimus (rapamycin).
- Other protocol-defined inclusion/exclusion criteria may apply
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | Female |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Percentage of patients progression-free after completion of 1st line treatment (everolimus + letrozole) |
| Time Frame: | 12 months after last patient recruited |
| Safety Issue: | |
| Description: | In this study Progression free survival is defined as the time from the date of enrollment to the date of first documented progression or death due to any cause. If a patient has not had an event, PFS will be censored at the date of the last adequate tumor assessment. |
Secondary Outcome Measures
| Measure: | Overall response rate and clinical benefit rate in patients receiving the first line study treatment (everolimus + letrozole) |
| Time Frame: | Baseline, every 8 weeks |
| Safety Issue: | |
| Description: | Overall response rate (ORR) is defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) according to RECIST. Clinical benefit rate (CBR) is defined as the proportion of patients with best overall response of CR, PR or stable disease with a duration of 24 weeks or longer according to RECIST. ORR and CBR will be calculated based on the full analysis set, using local radiologist's/investigator's tumor assessment. Patients with only non-measurable disease at baseline will be included in the numerator if they achieve a complete response |
| Measure: | Percentage of patients progression-free after completion of 2nd line treatment (everolimus + exemestane) |
| Time Frame: | Baseline, every 8 weeks |
| Safety Issue: | |
| Description: | In this study progression free survival in the second line is defined as the time interval between the start of the second line treatment and documented disease progression or death due to any cause reported during or after second line treatment |
| Measure: | Overall survival of patients receiving first line study treatment (everolimus + letrozole) |
| Time Frame: | Continuous during the study and every 12 weeks after last treatment |
| Safety Issue: | |
| Description: | The overall survival (OS) following first line treatment with Everolimus + Letrozole is defined as the time from the date of receiving first line study treatment to date of death due to any cause. |
| Measure: | Reduction in severity and duration of oral stomatitis |
| Time Frame: | Upon onset of 1st stomatitis, patient will complete diary daily until resolution of stomatitis |
| Safety Issue: | |
| Description: | Analysis for this objective will be based on Patient reported outcomes data for the first incidence of stomatitis AE. The mean, standard deviation and 95% confidence interval of each severity item in the questionnaire will be calculated at each day for the two therapeutic interventions for stomatitis groups and presented graphically. The duration of the first stomatitis incidence will be calculated using the dates reported in the PRO. |
| Measure: | Assessment of safety based on the frequency of adverse events that fall outside normal pre-specified ranges |
| Time Frame: | Continuous during the study, up to 28 days after last treatment |
| Safety Issue: | |
| Description: | The assessment of safety will be based mainly on the frequency of adverse events and on the number of laboratory values that fall outside of pre-determined ranges. Other safety data (e.g., electrocardiogram, vital signs) will be considered as appropriate. All safety data will be listed. For all safety analyses, the safety population will be used. |
| Measure: | Overall response rate and clinical benefit rate in patients receiving the second line study treatment (everolimus + exemestane) |
| Time Frame: | Baseline, every 8 weeks |
| Safety Issue: | |
| Description: | Overall response rate (ORR) is defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) according to RECIST. Clinical benefit rate (CBR) is defined as the proportion of patients with best overall response of CR, PR or stable disease with a duration of 24 weeks or longer according to RECIST. ORR and CBR will be calculated based on the full analysis set, using local radiologist's/investigator's tumor assessment. Patients with only non-measurable disease at baseline will be included in the numerator if they achieve a complete response |
| Measure: | Reduction in severity and duration of oral stomatitis |
| Time Frame: | Upon onset of 1st stomatitis and in countries where the alcohol-free dexamethasone solution (0.5mg/5ml) is commercially available, patient will be randomised to dexamethasone oral solution rinse or standard of care |
| Safety Issue: | |
| Description: | Analysis for this objective will be based on Patient reported outcomes data for the first incidence of stomatitis AE. The mean, standard deviation and 95% confidence interval of each severity item in the questionnaire will be calculated at each day for the two therapeutic interventions for stomatitis groups and presented graphically. The duration of the first stomatitis incidence will be calculated using the dates reported in the PRO. |
| Measure: | Percentage of patients with clinical benfit during extension phase |
| Time Frame: | Every 12 weeks up to 36 months |
| Safety Issue: | |
| Description: | Clinical benefit as assessed by investigator at scheduled visits to determine continuation of treatment |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- metastatic breast cancer, locally advanced breast cancer, HER2-, ER+, everolimus, Afinitor
Last Updated
April 14, 2021
