Non-Small Cell Lung Cancer, Small Cell Lung Cancer Clinical Trial
Official title:
Phase I Trial Of Cisplatin And KML-001 In Advanced Non-Small Cell Lung Cancer and Other Platinum Responsive Malignancies
This is a Phase I Clinical Trial. Phase I studies are designed to determine the amount of
investigational drugs that can be safely tolerated and to define the side effects that limit
the dose. The drug administered in this study is KML-001. It is a highly soluble, orally
available arsenic agent. It is currently being tested to determine its effects on telomerase
activity.
In other words, the purpose of this research study is to find the highest dose of KML001,
that can be given without causing severe side effects when it is combined with a standard,
commercially available anti-cancer drug called cisplatin.
Telomerase is the enzyme synthesizing the specific DNA sequences found at the telomeres in
the body's chromosomes. It is thus responsible for maintaining the length of telomeres.
Telomerase has been detected in human cancer cells and is found to be 10-20 times more active
than in normal body cells. This provides a selective growth advantage to many types of
tumors. If telomerase activity was to be turned off, then telomeres in cancer cells would
shorten, just like they do in normal body cells. This would prevent the cancer cells from
dividing uncontrollably in their early stages of development. In the event that a tumor has
already thoroughly developed, it may be removed and anti-telomerase therapy could be
administered to prevent relapse.
This study is being offered to patients with advanced cancer which has either no standard
therapy or which has progressed after treatment with one or more standard treatments.
The primary objective of this study :
To determine the maximum tolerated dose of KML001 in combination with cisplatin in patients
with advanced malignancy. This objective has been met. The study will be reopened with
expansion cohorts in advanced small cell lung cancer and non-small cell lung cancer to better
assess the activity of the combination, pending (Institutional Review Board (IRB) approval.
Secondary Objectives of the study:
To determine the pharmacokinetics of KML001 and cisplatin in this combination. To assess the
response rate, disease-free survival and survival associated with this regimen.
To correlate indications of patient benefit (response or stable disease) with pretreatment
specimens
The highest safest doses are determined by increasing the doses of cisplatin and KML001 in
successive groups of patients until at least some of them have serious side effects. All
patients on this study will receive the same dose of cisplatin, which is known to have
antitumor effects. The doses of KML001 will be increased in successive groups of patients. It
is possible that those entering the study early may receive suboptimal doses of KML001. At
the end of the study we hope to determine the appropriate dose of the KML001 in combination
with cisplatin, learn about its side effects and understand how the body metabolizes the
drug.
Laboratory data from the University of Maryland Greenebaum Cancer Center (UMGCC) has
demonstrated that the combination of KML001 and cisplatin is synergistic in lung cancer cell
lines. Cisplatin is the best established agent for the treatment of lung cancer and most
treatment regimens have been established with cisplatin (or its congener, carboplatin). This
synergism is particularly interesting given that there is an anti-telomere effect for
cisplatin.
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