A Phase I Study of Indenoisoquinolines LMP400 and LMP776 in Adults With Relapsed Solid Tumors and Lymphomas
OBJECTIVES:
Primary
- Define the maximum tolerated dose (MTD) of topoisomerase I inhibitors LMP400 and LMP776
in patients with relapsed solid tumors or lymphomas.
- Define the dose-limiting toxicities and toxicity profile of topoisomerase I inhibitors
LMP400 and LMP776 in these patients.
- Evaluate the effect of topoisomerase I inhibitors LMP400 and LMP776 on the
pharmacodynamic (PD) endpoint, γ-H2AX, in pre- and post-treatment tumor biopsy and skin
tissue samples.
- Compare topoisomerase I inhibitors LMP400 and LMP776 (when administered at the MTD), in
terms of the PD response, defined as the mean percent nuclear area that is γ-H2AX
positive in tumor biopsies, and the risk-benefit relationship, defined by the toxicity
profile vs PD dose-response relationship.
Secondary
- Obtain preliminary evidence of anti-tumor activity of topoisomerase I inhibitors LMP400
and LMP776.
- Characterize the pharmacokinetic profile of topoisomerase I inhibitors LMP400 and
LMP776.
OUTLINE: Patients are alternately assigned to 1 of 2 treatment groups.
- Group I: Patients receive topoisomerase I inhibitor LMP400 IV over 1 hour on days 1-5.
Courses repeat every 28 days in the absence of disease progression or unacceptable
toxicity.
- Group II: Patients receive topoisomerase I inhibitor LMP776 IV over 1 hour on days 1-5.
Courses repeat every 28 days in the absence of disease progression or unacceptable
toxicity.
Patients undergo blood, urine, tumor tissue, and skin tissue sample collection periodically
for correlative laboratory studies, including pharmacodynamic and pharmacokinetic studies
and γ-H2AX marker expression. Patients may also undergo hair follicle sample collection for
correlative laboratory studies.
After completion of study therapy, patients are followed for 30 days.
Interventional
Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose (MTD) of topoisomerase I inhibitors LMP400 and LMP776
Yes
Shivaani Kummar, MD
Principal Investigator
NCI - Medical Oncology Branch
Unspecified
CDR0000662682
NCT01245192
January 2010
Name | Location |
---|---|
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office | Bethesda, Maryland 20892-1182 |