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

Phase 1
18 Years
Not Enrolling

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Trial Information

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

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.

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.

Palliative radiation therapy indicated for disease and site. (More than one lesion may be
treated with radiation therapy.)

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

The site for radiotherapy, the index lesion, must have a measurable or evaluable tumor
documented no more than 4 weeks prior to having study-related procedures. More than one
lesion may be present and treated with radiotherapy. Additional lesions, not treated with
radiotherapy, may also be present. Previously irradiated sites will NOT be irradiated in
this study.

-Patient Characteristics-

Performance Status (ECOG/ZUBROD) 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.

Planned treatment site(s) has not had previous radiation therapy.

Patients must not have concurrent antitumor therapy other than that planned in the study.

No history of Grade 4 toxicity from prior radiation therapy. (Grade 3 toxicity from prior
radiation therapy, at investigator discretion.)

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:


Study Design:

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

Principal Investigator

Anatoly Dritschilo, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Georgetown University


United States: Food and Drug Administration

Study ID:




Start Date:

March 2001

Completion Date:

December 2004

Related Keywords:

  • Neoplasms
  • advanced malignancy
  • liposomes containing AON to c-raf messenger RNA
  • antisense oligodeoxynucleotide (AON)
  • LErafAON
  • Neoplasms



Fox Chase Cancer Center Philadelphia, Pennsylvania  19111
Temple University Cancer Center Philadelphia, Pennsylvania  19140
Georgetown University Washington, District of Columbia  20007-2197
University of Chicago Medical Center Chicago, Illinois  60637