University of Colorado. US: Head and neck cancer is among the few solid tumors whose incidence is
increasing in the U.S. and outcomes have been slow to improve. Results
of a phase 1 trial of the drug CUCD-101 with radiation and chemotherapy
were reported by the University of Colorado Cancer Center and 6 other U.S. cancer centers in the journal Clinical Cancer Research.
CUDC-101, currently being developed by Curis, Inc., works by inhibiting
two growth factors and an enzyme that effects DNA expression – EGFR,
Her2 and HDAC – all of which are overexpressed in many cancers,
including the target of this trial: the common type of especially
aggressive head and neck cancer that is not caused by the human
papilloma virus (HPV-) but rather by tobacco or alcohol.
“We pretty much threw the kitchen sink at it,” says Antonio Jimeno,
MD, PhD, the clinical trial’s senior author and director of the
University of Colorado School of Medicine’s Head and Neck Cancer
Clinical Research Program. In the phase 1 trial CUDC-101 was combined
with the standard of care for treatment of head and neck cancer, which
includes the chemotherapy drug cisplatin and radiation.
“Substantial technological advances in how we deliver radiation and
chemotherapy are now enabling the addition of targeted agents to improve
the cure rates and functional results in our patients,” Jimeno says.
Specifically, the study was performed in 12 medium- to high-risk head
and neck cancer patients. At 18 months median follow up, one patient’s
cancer had worsened, two had died, and nine remained free of disease.
Testing of blood and tumor samples showed that CUDC-101 had indeed
inhibited the action of EGFR, HDAC and Her2.
“By analyzing the molecular correlates obtained from our very
motivated and generous patients we saw that the drug was doing what it
was supposed to be doing. The fact that this complex trial was feasible
and didn’t significantly add to the toxicity of chemotherapy and
radiation that was given along with the study drug makes everybody more
excited about pursuing further trials,” Jimeno says.
“This is one of the most complex studies undertaken by the Head and
Neck Cancer program at the CU Cancer Center to date. We are proud to
have led patient enrolment to complete the trial, which defined the
proper dosing for this new drug. As much as the results, the trial
mechanics themselves contributed to our ability to publish these
findings in the leading journal for this kind of research with a trial
of only 12 patients,” Jimeno points out.
“Multidisciplinary care and access to clinical trials such as this
one are probably among the factors that contribute to higher cure rates
in dedicated, specialized Head and Neck Cancer Programs such as ours,”
Jimeno says.