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


Phase 1
18 Years
N/A
Not Enrolling
Both
Neoplasms

Thank you

Trial Information

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


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.

Inclusion Criteria


-Disease Characteristics-

Histologically-confirmed malignancy which has recurred or progressed after initial
definitive treatment and/or for which no curative therapy is available.

At least 30 days must have elapsed since receiving an investigational agent, at least 21
days since receiving any prior chemotherapy, and at least six weeks since receiving
nitrosourea-containing therapy; patient must have recovered from any related side effects.

Must have a measurable or evaluable tumor documented within 4 weeks prior to having
study-related procedures.

-Patient Characteristics-

Performance Status (ECOG) of 0 - 2.

Must be at least 18 years of age.

Must have adequate organ function: Absolute neutrophil count at least 1,500/mm3; Platelets
at least 100,000/mm3; Creatinine, Calcium, and total Bilirubin not higher than the upper
limit of normal; Liver enzymes AST and ALT not more than 2.5 x the upper limit of normal;
PT and aPTT not more than the upper limit of normal.

Life expectancy more than 12 weeks.

Must sign Informed Consent.

No concurrent antitumor therapy.

No infection requiring parenteral antibiotics; no HIV infection; no chronic hepatic
disease; and no seropositivity for Hepatitis B and Hepatitis C. (Use of prophylactic
antibiotics is permitted.)

No pregnant or lactating females. All females of child-bearing potential must use an
effective method of contraception.

No active Central Nervous System (CNS) metastasis. Neuroimaging is required only if
metastasis is suggested by history or physical examination.

Type of Study:

Interventional

Study Design:

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

Principal Investigator

Charles Rudin, M.D.

Investigator Role:

Principal Investigator

Authority:

United States: Food and Drug Administration

Study ID:

LErafAON-002

NCT ID:

NCT00024661

Start Date:

March 2001

Completion Date:

October 2004

Related Keywords:

  • Neoplasms
  • recurrent solid tumors
  • liposomes containing AON to c-raf protein (LErafAON)
  • Neoplasms

Name

Location

Temple University Cancer CenterPhiladelphia, Pennsylvania  19140
Georgetown UniversityWashington, District of Columbia  20007-2197
University of Chicago Medical CenterChicago, Illinois  60637