Study to Determine the Maximum Tolerated Dose of LErafAON in Patients With Advanced Solid Tumors

Neoplasms Clinical Trial

Official title: Study to Determine the Maximum Tolerated Dose of Liposome-Encapsulated C-RAF Antisense Oligodeoxynucleotide (LErafAON) in Patients With Advanced Solid Tumors

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 solid tumors will receive IV infusions of LErafAON over at least 60 minutes, once per week, for 8 weeks. In the absence of progression, patients may continue on weekly treatment. Pre-medications will be administered prior to each dose of study medication.

Cohorts of at least three patients will be entered at escalating dose-levels. Each cohort will be observed for at least ten days after receiving the first dose of treatment before additional patients are treated at a higher dose level. Patients will be followed for one month after receiving the last dose of study medication. The study will stop when a maximum tolerated dose (MTD) is identified. Dose escalation within a patient will not be allowed.

Clinical Trial Description

OBJECTIVES: I. Determine the toxicity and MTD of LErafAON when given by weekly IV infusion for 8 weeks in patients with advanced malignancies.

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

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

IV. Detect anti-tumor effects of intravenous LErafAON.

PROTOCOL OUTLINE: This is a Phase I Maximum Tolerated Dose (MTD) study for patients with recurrent solid tumor malignancies. Study medication will be administered by intravenous infusion over at least 60 minutes, once per week, for 8 weeks. In the absence of progression, patients may continue on weekly treatment. Pre-medications will be administered prior to each dose of study medication. Patients will be followed for one month after receiving the last dose of study medication. Patients with Complete Response (CR), Partial Response (PR), or Stable Disease (SD) at the Week 8 disease assessment may continue to receive study medication until disease progression (PD).

Cohorts of at least three patients will be entered at escalating dose-levels. Each cohort will be observed for at least ten days after receiving the first dose of treatment before additional patients are treated at a higher dose level. Patients will be followed for one month after receiving the last dose of study medication. The study will stop when a maximum tolerated dose (MTD) is identified. Dose escalation within a patient will not be allowed.

PROJECTED ACCRUAL: Estimated enrollment is 15-35 patients; 3 per dose level, expanded to 6 if 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: NCT00024661
• Study type: Interventional
• Source: INSYS Therapeutics Inc
• Status: Completed
• Phase: Phase 1
• Start date: March 2001
• Completion date: October 2004