Study of Erlotinib and Metformin in Triple Negative Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      Extended phase 1 trial of combined metformin and erlotinib in advanced triple negative breast
      cancer patients. The goals of the study are to establish the maximum tolerated combined
      dosing of erlotinib and metformin as well as deciding if there is a potential clinical
      utility of the combination in treating patients with triple negative breast cancer.
    

Detailed description: 
      Breast cancer has several different subtypes based upon measurement of expression of proteins
      found on the surface of the cancer cells. Cancers that lack expression of three of these
      proteins, namely the estrogen receptor, progesterone receptor, and human epidermal growth
      factor receptor 2 (HER2), are termed triple negative. By studying the molecular attributes of
      breast cancer cells from a large group of breast cancer patients, a profile of markers
      enriched in triple negative breast cancers (TNBC) was discovered. This profile includes loss
      of expression of the protein, Phosphatase and Tensin homolog (PTEN), increased expression of
      the protein, epidermal growth factor receptor (EGFR), and disruption of the cells ability to
      repair DNA. These alterations also allow the tumor to thrive and likely evade treatment.
      Observation has been made that the drug combination of metformin and erlotinib can inhibit
      triple negative cells with these alterations. A clinical trial will be conducted to test the
      ability of patients to tolerate the treatment (Phase I trial). This trial will be available
      to triple negative breast cancer patients with metastatic disease. Other goals of the study
      will be to confirm that the drugs are working properly and whether or not there are enough
      responses to the treatment to warrant additional studies. If the treatment proves to be
      effective, even if only in a subset of triple negative patients, future studies will focus on
      validating biomarkers that can identify patients that will respond to the drug combination,
      as well as discovering how cells become resistant to the treatment. The research has the
      potential to advance a new effective treatment for a highly lethal disease and thus could
      prolong patient survivals while maintaining a high quality of life.
    

Intervention name(s): Metformin; Erlotinib
Intervention type(s): Drug; Drug
Intervention description(s): Due to frequent GI upset in patients starting metformin the dose will be titrated up to the assigned dose level. The first metformin dose level will be 850 mg twice daily and be escalated to its maximum FDA approved dose of 850 mg three times daily. Dose escalation will follow the standard 3 + 3 design. Dose limiting toxicities will be determined during the first 5 weeks of therapy.; Erlotinib dosing will start and remain at 150 mg daily.
Other intervention name(s): Glucophage; Tarceva
Intervention MeSH terms: Metformin; Erlotinib Hydrochloride
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Triple Negative; Basal-like