NeoplasmsPhase 1NCT00024648
Study to Determine Maximum Tolerated Dose of LErafAON Combined With Radiotherapy in Patients With Advanced Malignancies
A Phase 1 study testing LErafAON in people with Neoplasms, run by INSYS Therapeutics Inc at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- LErafAON
- How many people
- 25 participants
- Where
- 4 sitesUnited States
- Study dates
- Mar 2001to Dec 2004
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
-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.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of Chicago Medical Center
Chicago, Illinois, 60637
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Temple University Cancer Center
Philadelphia, Pennsylvania, 19140
Georgetown University
Washington D.C., District of Columbia, 20007
About this study
Official title: 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.
Read the 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.
- Conditions
- Neoplasms
- Being tested
- LErafAON
- Keywords
- advanced malignancy, liposomes containing AON to c-raf messenger RNA, antisense oligodeoxynucleotide (AON), LErafAON
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LErafAONDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2001 (estimated)
- Study startMar 2001
- Study completionDec 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants
Sponsor and investigators
- Lead sponsor
- INSYS Therapeutics Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Georgetown University
- Investigators
- Anatoly Dritschilo, M.D., Principal investigator, Georgetown University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00024648
- Sponsor's protocol ID
- LErafAON-001
- Status last verified
- Apr 2011
- First submitted
- 24 Sep 2001
- Last updated
- 13 Apr 2011
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study to Determine the Maximum Tolerated Dose of LErafAON in Combination With Radiotherapy in Patients With Advanced Malignancies
- ClinicalTrials.gov ID
- NCT00024648
- Acronym / sponsor ID
- LErafAON-001
- Conditions
- Neoplasms
- Keywords
- advanced malignancy, liposomes containing AON to c-raf messenger RNA, antisense oligodeoxynucleotide (AON), LErafAON
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants
- Lead sponsor
- INSYS Therapeutics IncIndustry (pharma, biotech, devices)
- Collaborators
- Georgetown University
- Study start
- Mar 2001
- Study completion
- Dec 2004
- First posted
- 25 Sep 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LErafAON | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2011.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anatoly Dritschilo, M.D. principal investigator
Georgetown University
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LErafAON in people with Neoplasms, run by INSYS Therapeutics Inc at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Apr 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2011.