Study to Determine Maximum Tolerated Dose of LErafAON Combined With Radiotherapy in Patients With Advanced Malignancies
Status:
Completed
Trial end date:
2004-12-01
Target enrollment:
Participant gender:
Summary
LErafAON is a liposome encapsulated c-raf antisense oligonucleotide. Raf-1 is a protein
produced by human cells, both normal and cancerous, which may help protect tumor cells from
radiation. Antisense oligonucleotides are very specific drugs, which can decrease the amount
of a certain target protein by blocking the gene that makes it. Antisense oligonucleotide to
raf gene can reduce the amount of Raf-1 protein in tumor cells. Liposomes are tiny globules
of fat, which can carry drugs in the body. The experimental agent LErafAON is composed of
liposomes carrying antisense oligonucleotide against the Raf-1 protein. It is hoped that
decreased Raf-1 in the cancer cells will make them more sensitive to the radiation therapy.
Patients with advanced malignancies will receive daily IV infusions of LErafAON for 2 weeks
(total of 10 doses) during clinically indicated palliative radiotherapy. Cohorts of at least
three patients will be entered at escalating dose-levels. Each cohort will be observed for
toxicity for at least two weeks after completion of treatment with study medication before
the next cohort is enrolled. The study will be stopped when a maximum tolerated dose (MTD) is
identified. Dose escalation within a patient will not be allowed. Safety and supportive care
requirements will be assessed.