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Trial record 48 of 56 for:    insys

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00024648
Recruitment Status : Completed
First Posted : September 25, 2001
Last Update Posted : April 13, 2011
Sponsor:
Collaborator:
Georgetown University
Information provided by:
INSYS Therapeutics Inc

Tracking Information
First Submitted Date  ICMJE September 24, 2001
First Posted Date  ICMJE September 25, 2001
Last Update Posted Date April 13, 2011
Study Start Date  ICMJE March 2001
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE Not Provided
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00024648 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Determine Maximum Tolerated Dose of LErafAON Combined With Radiotherapy in Patients With Advanced Malignancies
Official Title  ICMJE Phase I Study to Determine the Maximum Tolerated Dose of LErafAON in Combination With Radiotherapy in Patients With Advanced Malignancies
Brief 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.

Detailed 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neoplasms
Intervention  ICMJE Drug: LErafAON
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Enrollment  ICMJE
 (submitted: June¬†23,¬†2005)
25
Original Enrollment  ICMJE Same as current
Study Completion Date  ICMJE December 2004
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

-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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00024648
Other Study ID Numbers  ICMJE LErafAON-001
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE INSYS Therapeutics Inc
Collaborators  ICMJE Georgetown University
Investigators  ICMJE
Principal Investigator: Anatoly Dritschilo, M.D. Georgetown University
PRS Account INSYS Therapeutics Inc
Verification Date April 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP