Study to Determine Maximum Tolerated Dose of LErafAON Combined With Radiotherapy in Patients With Advanced Malignancies
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|ClinicalTrials.gov Identifier: NCT00024648|
Recruitment Status : Completed
First Posted : September 25, 2001
Last Update Posted : April 13, 2011
|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|
|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|
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.
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
|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 Status ICMJE||Completed|
|Original Enrollment ICMJE||Same as current|
|Study Completion Date ICMJE||December 2004|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
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.
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.
|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|
|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|
|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