Modulation of Response to Hormonal Therapy With Lapatinib and/or Metformin in Patients With Metastatic Breast Cancer
Status:
Terminated
Trial end date:
2013-12-01
Target enrollment:
Participant gender:
Summary
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 therapy + metformin + lapatinib with a ratio 1:1:1.
For each arm of the study the following sample size is required:
- First step: 23 patients, for a total of 69 patients in all 3 arms
- Second step: further 33 patients, for a total of 168 patients in all 3 arms.