Study to Determine Maximum Tolerated Dose of LErafAON Combined With Radiotherapy in Patients With Advanced Malignancies

Neoplasms Clinical Trial

Official title: Phase I Study to Determine the Maximum Tolerated Dose of LErafAON in Combination With Radiotherapy in Patients With Advanced Malignancies

Status Completed

Clinical Trial 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.

Clinical Trial Description

OBJECTIVES: I. Determine the toxicity and MTD of LErafAON administered in daily I.V. infusions, in combination with radiotherapy, to patients with advanced malignancies.

II. Characterize the plasma pharmacokinetics of LErafAON after IV infusion.

III. Assess in vivo inhibition of Raf-1 protein by LErafAON.

IV. Determine efficacy in radiated and non-radiated tumors.

PROTOCOL OUTLINE: This study is a traditional Phase I MTD study. Cohorts of at least three patients will be entered at escalating dose-levels. Patients will receive daily IV infusions of LErafAON for 2 weeks (total of 10 doses). Each cohort will be observed for at least two weeks post treatment with study medication to allow for observation of toxicity before the next cohort is enrolled. Dose escalation will proceed until the MTD is identified. Dose escalation within a patient will not be allowed.

PROJECTED ACCRUAL: Up to 27 patients; at least 3 per dose level, expanded to 6 if dose-limiting toxicity (DLT) occurs. ;

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasms

• NCT number: NCT00024648
• Study type: Interventional
• Source: INSYS Therapeutics Inc
• Status: Completed
• Phase: Phase 1
• Start date: March 2001
• Completion date: December 2004