Overview

This trial is active, not recruiting.

Condition hormone receptor positive breast cancer
Treatments everolimus, letrozole, exemestane, alcohol-free dexamethasone mouth rinse
Phase phase 2
Targets HER, mTOR, FKBP-12
Sponsor Novartis Pharmaceuticals
Start date March 2013
End date December 2016
Trial size 202 participants
Trial identifier NCT01698918, 2012-003065-17, CRAD001Y24135

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(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 RAD001
Everolimus will be self-administered as a daily dose of 10mg (two 5mg tablets) taken orally continuously from study day 1 until progression of disease, unacceptable toxicity or withdrawal of consent. Everolimus should be taken at the same time every day. Everolimus tablets should be swallowed whole with a glass of water once daily, either consistently with food or consistently without food. Tablets should not be chewed or crushed.
letrozole Femara
1st line study treatment: Letrozole will be self administered as a daily dose of 2.5mg continuously from study day 1 until disease progression, unacceptable toxicity or withdrawal of consent and should be taken at the same time every day, consistently with or without food. Everolimus and letrozole tablets should be taken together.
exemestane Aromasin
2nd Line Study Treatment: If patients progress on everolimus + letrozole, patients will be offered everolimus + exemestane. Exemestane will be self administered as a daily dose of 25mg taken orally continuously until disease progression, unacceptable toxicity or withdrawal of consent and should be taken at the same time every day after a meal. Everolimus and exemestane tablets should be taken together.
alcohol-free dexamethasone mouth rinse alcohol-free dexamethasone 0.5 mg/5ml
At the onset of symptoms suggestive of stomatitis patients must contact the study site. Upon confirmation of stomatitis at the site, patients in countries where the alcohol-free 0.5mg/5ml dexamethasone oral solution is commercially available will be randomly assigned to take either dexamethasone 0.5 mg/5ml mouth rinse or the standard of care used to treat stomatitis at the patient's center. The mouth rinse will be self administered at a daily dose of 10ml 3 times per day. Patients will be instructed to swish and expectorate the mouth rinse. Patients will also be instructed to fill out the Oral Stomatitis Daily Questionnaire (OSDQ) at home every day until the patient recovers. The mouth rinse will be self administered at a daily dose of 10ml 3 times per day.Patients will be instructed to swish and expectorate the mouth rinse.

Primary Outcomes

Measure
Percentage of patients progression-free after completion of 1st line treatment (everolimus + letrozole)
time frame: 12 months after last patient recruited

Secondary Outcomes

Measure
Overall response rate and clinical benefit rate in patients receiving the first line study treatment (everolimus + letrozole)
time frame: Baseline, every 8 weeks
Percentage of patients progression-free after completion of 2nd line treatment (everolimus + exemestane)
time frame: Baseline, every 8 weeks
Overall survival of patients receiving first line study treatment (everolimus + letrozole)
time frame: Continuous during the study and every 12 weeks after last treatment
Reduction in severity and duration of oral stomatitis
time frame: Upon onset of 1st stomatitis, patient will complete diary daily until resolution of stomatitis
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
Overall response rate and clinical benefit rate in patients receiving the second line study treatment (everolimus + exemestane)
time frame: Baseline, every 8 weeks
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

Eligibility Criteria

Female participants at least 18 years old.

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

Additional Information

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
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Novartis.