Modulation of Response to Hormonal Therapy With Lapatinib and/or Metformin in Patients With Metastatic Breast Cancer

Sponsor
Fondazione Michelangelo
Study ID
NCT01477060
Phase
PHASE2
Status
Terminated

Conditions

Eligibility Criteria

Sex
FEMALE
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Lapatinib — DRUG
    1250 mg/ die, os
  • Metformin — DRUG
    1500 mg/die, os

Study Details

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.

Key Dates

Start date
Nov 30, 2011
Status verified
Feb 2014
Primary completion
Dec 31, 2013
Completion
Dec 31, 2013

Study Design

Enrollment
32 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Other: ARM A - Lapatinib
    hormonal therapy + lapatinib (1250mg/die) until disease progression or extraordinary medical circumstances occur or intolerable toxicities occur or the patient withdraws consent.
  • Other: ARM B - Metformin
    Hormonal therapy + metformin until disease progression or extraordinary medical circumstances occur or intolerable toxicities occur or the patient withdraws consent.
  • Other: ARM C - Lapatinib + Metformin
    Hormonal therapy + lapatinib + metformin until disease progression or extraordinary medical circumstances occur or intolerable toxicities occur or the patient withdraws consent.

Primary Outcome Measure

Rate of patients free from disease progression [ Time Frame: 3 months from randomization ]

Related Studies