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

This study has been completed.
Information provided by:
INSYS Therapeutics Inc Identifier:
First received: January 4, 2005
Last updated: June 30, 2011
Last verified: June 2011

The primary purpose of this study is to identify a dose of Liposome Entrapped c-raf Antisense Oligonucleotide Easy-to-Use (LErafAON-ETU) which maximizes potential benefits of the compound to patients with advanced cancer, without compromising their safety. This study will also assess the processing of LErafAON-ETU by the body over time. Patients will receive an intravenous infusion of LErafAON-ETU each week. Multiple blood samples will be taken for pharmacokinetic analysis during the first treatment; two samples will be taken during both the second and third treatments. Patients will be eligible to continue treatment until the occurrence of unacceptable toxicity or disease progression.

In LErafAON-ETU, antisense oligonucleotides specific to c-raf, are associated with liposomes, which are microscopic membrane-like structures created from lipids (fats). Raf-1 is a protein which plays a critical role in many aspects of cellular activation and growth. Therefore, it is thought to be an important factor that may support tumor development. LErafAON-ETU potentially limits the ability of a cell to produce the Raf-1 protein.

Condition Intervention Phase
Drug: LErafAON-ETU
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of an Easy-to-Use Intravenous Formulation of Liposome Entrapped C-raf Antisense Oligonucleotide (LErafAON-ETU) Administered on a Weekly Schedule in Patients With Advanced Cancer

Resource links provided by NLM:

Further study details as provided by INSYS Therapeutics Inc:

Primary Outcome Measures:
  • To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of LErafAON-ETU.

Secondary Outcome Measures:
  • To determine the pharmacokinetics of raf antisense oligonucleotide after intravenous administration of LErafAON-ETU
  • To determine any anti-tumor effects of LErafAON-ETU.

Estimated Enrollment: 40
Study Start Date: December 2004
Study Completion Date: November 2010
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Detailed Description:
This Phase I, open-label, dose-escalation study is designed to determine the maximum tolerated dose of LErafAON-ETU in patients who have advanced cancer considered unresponsive to available, conventional modalities or treatments. LErafAON-ETU will be administered as an IV infusion once weekly for 3 consecutive weeks (a Treatment Cycle). A complete pharmacokinetic profile of raf-1 antisense oligonucleotide will be assessed in week 1 only; limited pharmacokinetic sampling will be done prior to and at the end of infusion in weeks 2 and 3 only. Tumor/disease evaluation will be performed upon completion of 6 infusions (2 Cycles). Dose escalation will not occur until the safety and tolerability at a given dose level has been confirmed for 1 Cycle.

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

To be included in this study, patients must meet the following criteria:

  • Be ≥18 years of age.
  • Have advanced (local and/or metastatic) histologically documented cancer not considered responsive to available conventional modalities or treatment (i.e., no life prolonging therapy or therapy with a greater potential for patient benefit is available).
  • Have an ECOG Performance status of 0-1.
  • Have a life expectancy of >12 weeks.
  • Have recovered from acute toxicities of prior treatment: *No treatment with radiotherapy or with cytotoxic or biologic agents within 3 weeks prior to study entry. At least 2 weeks must have elapsed since any prior surgery or granulocyte-stimulating growth factor therapy. Chronic treatment with non-investigational gonadotropin-releasing hormone agonists or other hormonal or supportive care is permitted. Concurrent bisphosphonate treatment is permitted if initiated ≥90 days prior to study entry. *Chronic Grade 1 toxicities due to prior treatment or other causes are permitted.
  • Be in adequate condition as evidenced by the following clinical laboratory values:

    • Absolute neutrophil count (ANC) ≥1,500/mm³,
    • Hemoglobin ≥9.0 g/dL,
    • Platelets ≥125,000/mm³,
    • PT, aPTT, creatinine, calcium, and total bilirubin ≤the institutional upper limit of normal (ULN),
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x ULN,
    • Alkaline phosphatase ≤2.5 x ULN
  • Patients (male and female) must be willing to practice an effective method of birth control during the study.
  • Patient must understand the investigational nature of this study and sign an Institutional Review Board (IRB) approved informed consent form prior to the performance of any study specific procedure.

Exclusion Criteria:

Patients are excluded from this study for the following:

  • Active uncontrolled bleeding or bleeding diathesis (e.g., active peptic ulcer disease).
  • Any active infection requiring parenteral or oral antibiotic treatment.
  • Known infection with human immunodeficiency virus or hepatitis virus.
  • Active heart disease including myocardial infarction within the previous 6 months, symptomatic coronary artery disease, arrhythmias currently requiring medication, or congestive heart failure.
  • Known or suspected active central nervous system metastasis (patients stable 8 weeks after completion of treatment for central nervous system metastasis are eligible).
  • Requiring immediate palliative treatment of any kind, including surgery and/or radiotherapy
  • Concurrent anti-tumor therapy (except for chronic hormonal anti-tumor therapy).
  • Treatment with any investigational drug within the 30-day period prior to enrollment in the study.
  • Known hypersensitivity to any of the components of LErafAON-ETU.
  • Prior treatment with LErafAON (previous sonicated formulation).
  • Female patients who are pregnant or breast-feeding.
  • Unwilling or unable to follow protocol requirements.
  • Any consideration which in the Investigator's opinion deems the patient an unsuitable candidate to receive study drug.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00100672

United States, Arizona
premiere Oncology-Arizona
Scottsdale, Arizona, United States, 85260
United States, California
Premiere Oncology-Santa Monica
Santa Monica, California, United States, 90404
Sponsors and Collaborators
INSYS Therapeutics Inc
  More Information Identifier: NCT00100672     History of Changes
Other Study ID Numbers: LErafAON-ETU-104-R02 
Study First Received: January 4, 2005
Last Updated: June 30, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by INSYS Therapeutics Inc:
Signal transduction
Advanced neoplasm
Advanced cancer
Refractory cancer
Metastatic cancer processed this record on May 25, 2016