CINCINNATI—A clinical trial created and being
conducted by Cincinnati Cancer Center (CCC) and University of Cincinnati (UC)
Cancer Institute researchers is attempting to determine if certain doses of an
anti-malarial drug used in combination with standard therapy for advanced
cancers could be beneficial for patients.
"Chloroquine, or CQ, prevents the development
of malaria parasites in the blood. Doctors use it to both prevent and treat
malaria,” says Nagla Karim, MD, PhD, member of the CCC, assistant professor in
the division of hematology oncology at the UC College of Medicine, member of
the UC Cancer Institute and principal investigator on this study. "CQ has been
receiving increased attention since cancer biologists noted its role as an
inhibitor of autophagy—when cells eat themselves.
"It has been thought that inhibition of
different stages of autophagy may result in different outcomes. Inhibition during
the early stage of autophagy will rescue cancer cells while inhibition in the
late stage of autophagy will lead to cell death, so manipulation of autophagy
has become an exciting area for the development of new therapeutic strategies.
CQ specifically inhibits autophagy in a mechanism distinct from other autophagy
Karim adds that CQ has also recently been
identified as a chemosensitizer, meaning it allows chemotherapy to work more
effectively in certain patients, while used in combination with other
"Additionally, chloroquine mildly suppresses
the immune system and is used in some autoimmune disorders, such as rheumatoid
arthritis and lupus,” she says. "Therefore, the great advantage of CQ over
other inhibitors of autophagy is the possibility of introducing it into the
clinical setting of cancer therapy without the need for animal or phase-1
is also being studied as a treatment in patients with relapsed multiple
myeloma, pancreatic cancer, brain tumors (glioblastoma multiforme) and small
cell lung cancer.”
In this trial, eligible patients will be
given Chloroquine orally at different dose levels for a total of four cycles
(21-day cycles). Chemotherapy (carboplatin/Gemcitabine) will be given during
the same time. Recommended dose modifications are based on pretreatment
Additional fifth and sixth cycles of
Carboplatin and Gemcitabine without the addition of chloroquine will continue
in the case of a patient’s response to therapy.
The additional cost of chloroquine will be
covered by the division of hematology oncology as a part of the research
expenses of the study.
"This clinical trial is
investigator-initiated and is not being conducted anywhere else in the
country,” says Karim. "That is a benefit of the Phase I Experimental
Therapeutics Program—we might be able to offer a treatment that works for a
patient who might not have been experiencing success with standard therapies.”
The UC Cancer Institute Phase I Experimental
Therapeutics Program offers first-in-human testing of new therapeutic drugs for
patients with solid tumors who have failed standard medical therapies. Phase-1
clinical research trials are the first step in moving tested scientific
concepts from the laboratory bench to bedside, and typically include less than
50 people. Trials are intended to evaluate safe dosages, method of
administration (oral or injection) and frequency.
"We hope this trial leads to another
beneficial therapy for patients with advanced cancers,” Karim says.