Modulation of Response to Hormonal Therapy With Lapatinib and/or Metformin in Patients With HER2-negative, ER and/or PgR Positive Metastatic Brest Cancer With Progressive Disease After First-line Therapy
Abstract
Target Population: female patients with HER2-negative, ER and/or PgR positive breast cancer in progression after first-line hormonal therapy.
The study rationale is based on the potentiality of reversing endocrine-resistance by Lapatinib
* Activity on compensatory-adaptive mechanisms of hyperactivity of signals generated by HER2 family
* Modulation of energy balance and signals associated to survival through AMPK activation (via Calmodulin) Metformin
* Indirect mechanism, through reduced insulin receptors and IGFR stimulation, with reduces proliferative effects downstream
* Direct mechanism, through AMPK activation (via LKB1), with reduced protein synthesis (mTOR inhibition) and increased availability of intracellular energy Lapatinib and Metformin
* AMPK "Double"activation, through different potentially additional mechanisms.
* Inhibition of proliferative mechanisms for interference on various intracellular target
* IR (A e/o B); IGFR
* EGFR; HER2
Primary objectives :
1\. To assess the rate of patients free from disease progression at 3 months from randomization
Secondary objectives :
1. To assess the overall response rate
2. To assess the duration of response
3. To assess 3-years overall survival rate
4. To assess tolerability of each proposed treatment Female patients with HER2-negative, ER and/or PgR positive breast cancer in progression after first-line hormonal therapy will randomized to receive: hormonal therapy + lapatinib or hormonal therapy + metformin or hormonal…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 32 participants or records.
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