“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 inhibitors.”
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 anti-cancer drugs.
“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 studies. It 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 hematologic restrictions.
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.
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