Safety and Tolerability of Everolimus in Combination With Eribulin in Triple-negative Breast Cancers
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|ClinicalTrials.gov Identifier: NCT02616848|
Recruitment Status : Unknown
Verified November 2015 by Giandomenico Roviello, Istituti Ospitalieri di Cremona.
Recruitment status was: Recruiting
First Posted : November 30, 2015
Last Update Posted : November 30, 2015
Treatment of triple negative breast cancer (TNBC) relies heavily on different regimes of chemotherapeutic agents but remains one of the most challenging subtypes to treat because of the lack of specific therapies. Despite being sensitive to chemotherapy, many women with TNBC relapse quickly, developing locoregional recurrence or visceral metastasis. Toxicity and chemotherapy resistance are still major limitations in the treatment of patients with TNBC. Despite current trend of targeted therapy development, cytotoxic agents are a mainstay of treatment of patients with breast cancer. Further research into new combination of different compounds is needed in order to maximise benefit, whilst minimising toxicity.
The phosphoinositide 3-kinase (PI3K) pathway is associated with resistance to a variety of anti-tumor agents. This has been described pre-clinically with cytotoxic chemotherapeutic agents with varying mechanisms of action including taxanes, and DNA-damaging agents. In the clinic, activated PI3K in tumors has been correlated with decreased response to therapy and worse clinical outcomes.
The recent biological findings suggest that a PI3K/mammalian target of rapamycin (mTOR) inhibitors may increase the efficacy of chemotherapeutic agents which are considered standard of care (SOC) for the treatment of several solid tumors.
The study by the Unitaed state Oncology Research of Huston and the Sarah Cannon Cancer Center randomized 1830 patients with high risk breast cancer to the standard adjuvant treatment with adriamicin cyclophosphamide followed by paclitaxel versus the experimental adjuvant treatment with adriamicin taxotere (AT) followed by paclitaxel. At 5-years of follow up, the AT followed by paclitaxel produced significantly better overall survival (p=0.054) and improved disease free survival (DFS) (p=0.19). Among TNBC patients both DFS (74% versus 79%, p=0.1) and overall survival (OS) (79% versus 84%, p=0.037) were better in experimental arm. However, the main reasons for patients being taken off study treatment were toxicity (85 patients in the control arm and 128 in the experimental arm) and consent withdrawal (18 patients in the control arm and 30 patients in the experimental arm). For this reason, research into alternatives has intensified, thus resulting in the discovery and development of new compounds with a more tolerable profile as compared with paclitaxel.
Among the total of 762 patients enrolled into Eisai Metastatic Breast Cancer Study Assessing Physician's Choice Versus E7389 (EMBRACE) trial, 19% had TNBC. Of note, eribulin was most effective in hormone receptor-negative patients and in TNBC patients, who had a 29% risk reduction. Treatment with eribulin was well tolerated. Neutropenia, leucopenia, peripheral neuropathy, and asthenia/fatigue were the most common adverse events reported at Common Terminology Criteria for Adverse Events (CTCAE) grades 3 and 4. Neutropenia was the most common adverse events reported at CTCAE grade 4 in the eribulin group (24.1%).
Based on findings to date, eribulin is an attractive agent, and its role in combination with new compounds such as everolimus deserves further investigations. Their combination might lead to more profound effects on tumor cell biology of triple negative metastatic breast cancer.
During the course of the trial, dose reductions for each combination will be permitted in patients who cannot tolerate the starting dose
|Condition or disease||Intervention/treatment||Phase|
|Triple Negative Breast Cancer||Drug: Everolimus Drug: Eribulin||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||1 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Study Start Date :||November 2015|
|Actual Primary Completion Date :||November 2015|
|Experimental: Everolimus, Eribulin||
- The recommended dose of everolimus in combination with eribulin in metastatic triple negative breast cancer [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months ]
- Signs of anti-tumor activity of the administered treatment [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months ]
- Maximum Plasma Concentration [Cmax] between everolimus and eribulin [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months ]
- Safety profile of the combination and thus to monitor the potential Adverse Events and vital sign abnormalities; [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months ]
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02616848
|Contact: Daniele Generali, Professor||+390372 firstname.lastname@example.org|
|Cremona, Lombardia, Italy, 26100|
|Contact: Daniele Generali, Prof email@example.com firstname.lastname@example.org|