According to the Cancer Atlas, lung cancer remains the major cancer among the 10.9 million
new cases of cancer diagnosed annually worldwide. The mortality from lung cancer is greater
than the combined mortality for breast, colon and prostate cancer combined. Most patients
with metastatic non-small-cell lung cancer (NSCLC) are treated with platinum-based
chemotherapy regimens. The drug combination of cisplatin and docetaxel is one of the commonly
used regimens in metastatic NSCLC. Although both drugs are powerful disruptors of cell
growth, positive therapeutic response rates to this therapy remain low for NSCLC patients,
from 25% to 30%. While adding new biologics such as bevacizumab to the current treatment
standard can improve treatment response, median survival for advanced NSCLC patients
receiving this type of treatment remains low at under 12 months. Research studies have
demonstrated that Vitamin D, and it's signaling pathways are important biological targets in
cancer therapeutics. In vitro and in vivo calcitriol (1, 25 dihydroxycholecalciferol) is
antiproliferative and potentiates the antitumor effects of cytotoxic agents (e.g. taxanes,
platinum analogues). We have shown that administration of high doses of calcitriol and
cisplatin is feasible and associated with complete tumor regressions in dogs with spontaneous
cancers. Calcitriol has also shown to be synergistic with docetaxel both in preclinical as
well as in a recent phase II clinical trial in prostate cancer. Based on these results and
other supporting data from studies indicating that calcitriol functions as a potent and well
tolerated anti-tumor agent when used in combination with drugs likes cisplatin and docetaxel,
we hypothesize that introducing calcitriol into treatment regimes for NSCLC patients has the
potential to demonstrably improve treatment response for these patients. The overall goals
for conducting this phase I/II clinical study will be (1) to determine the maximum tolerated
dose (MTD) and dose limiting toxicities (DLT) of calcitriol in combination with
cisplatin/docetaxel in patients with advanced NSCLC, (2) to assess the response rates of
patients with advanced NSCLC to the combination of calcitriol with cisplatin/docetaxel, (3)
to evaluate the pharmacokinetics (PK) of administering calcitriol intravenously at the MTD,
and (4) to evaluate correlations between calcitriol PK and changes on specific coding regions
of the gene associated with calcitriol breakdown.
Phase:
Phase 1/Phase 2
Details
Lead Sponsor:
University of Michigan Cancer Center University of Michigan Rogel Cancer Center