Carcinoma, Non-squamous Non-small-cell Lung Clinical Trial
Official title:
METformin With a Carbohydrate Restricted Diet in Combination With Platinum Based Chemotherapy in Stage IIIB/IV Non-squamous Non-small Cell Lung Cancer (NS-NSCLC) - METRO Study
Subjects, who are eligible for the study, will be treated with four cycles of carboplatin
AUC of 5 IV and pemetrexed 500mg/m2 IV every 21 days +/- 2 days as per the standard of care.
Subjects who have not progressed after four cycles by radiological assessment (partial
response or stable disease) will receive single agent pemetrexed 500mg/m2 IV q 21 days +/- 2
days as maintenance therapy and as the standard of care until disease progression or subject
cannot tolerate.
Metformin will be given as 500 mg pills starting on day 1 of chemotherapy. Starting dose
will 500mg po bid (1000mg/day). If tolerating (see below for dose reduction), the dose will
be escalated to 1000mg po qam and 500mg po qpm (1500mg/day) from days 8 to 14. If still
tolerating, the dose will be escalated to 2 500mg pills twice a day for a total dose of
2000mg/day from days 15 until end of the study. This dose has been found to be safe in
healthy controls and in subjects treated with chemotherapy.
Metformin, an oral biguanide agent used for the treatment of non-insulin-dependent diabetes
mellitus, is now prescribed to more than 120 million people worldwide. Its glucose lowering
effects result from both inhibition of liver gluconeogenesis and increased insulin
sensitivity in peripheral tissue[5]. Metformin has limited adverse effects with little or no
risk of hypoglycemia in healthy, nondiabetic controls. In addition to its anti-diabetic
properties, metformin has demonstrated both chemopreventative and therapeutic effects in
both prostate and breast cancer.
The role of metformin as a preventative and therapeutic agent in lung cancer is beginning to
be assessed. A recent epidemiological study from Taiwan demonstrated a 39-45% decreased risk
of lung cancer in diabetic patients being treated with antidiabetic drugs including
metformin versus those not taking these agents[12]. These studies have triggered preclinical
and clinical observational trials that further support metformin's potential as an
antineoplastic agent. Two observational studies in humans have reinforced metformin's
potential role as a therapeutic agent in lung cancer. In the first, Mezzone et al. showed
that diabetic patients with lung cancer previously treated with metformin or
thiazolidinediones had a lower incidence of metastatic disease at the time of diagnosis and
a reduced risk of death compared to those who did not receive the same treatment[15]. More
recently, a retrospective study performed by Tan et al. evaluated the outcomes of three
groups of diabetic patients with NSCLC treated with first line chemotherapy and receiving
various diabetic drugs. In this study, patients treated with chemotherapy with metformin had
superior outcomes compared to those patients treated with chemotherapy with insulin or with
drugs other than metformin (OS, 20 months vs. 13.1 months vs 13.0 months, respectively,
p=0.007)[16]. The remarkable activity of this agent in both preclinical and clinical lung
cancer models as well as its low toxicity and tolerability in non- diabetic patients
warrants further prospective studies evaluating the therapeutic efficacy with platinum based
chemotherapy in NSCLC.
;
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Active, not recruiting |
NCT03976323 -
Study of Pembrolizumab With Maintenance Olaparib or Maintenance Pemetrexed in First-line (1L) Metastatic Non-squamous Non-Small-Cell Lung Cancer (NSCLC) (MK-7339-006, KEYLYNK-006)
|
Phase 3 |