Colorectal NeoplasmsPhase 1/2NCT00035919
Safety and Efficacy of Targeted Gene Transfer in Colorectal Cancer Metastatic to Liver
A Phase 1/2 study testing Mx-dnG1 Retroviral Vector in people with Colorectal Neoplasms, run by University of Southern California.
Trial summary
This is a Phase I safety study of a gene transfer drug for colorectal cancer that has spread to the liver. The main purpose of this study is to determine if it is safe to give this new intervention to persons with cancer, but we will also look for indications that the drug is effective. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Neoplasms
- What is being tested?
- Mx-dnG1 Retroviral Vector
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Nov 2002to Oct 2003
- Phase
- Phase 1/2
- 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
Who may be able to join
None listed.
Who cannot join
- Prior malignancy, except for non-melanoma skin cancer, stage I breast cancer, CIS of cervix from which the patient has been disease free for 5 years.
- Woman who are pregnant or nursing
- Fertile patients unless they agree to use barrier contraception (condoms and spermicide jelly) during the vector infusion period and for six weeks after infusion.
- Patients with medical, psychiatric, or social conditions that would compromise successful adherence to this protocol.
- Patients with indwelling biliary stents or a recent history of cholangitis, hepatitis, presence of disseminated intravascular coagulopathy, or HIV infection. Patients must not have a history of recent myocardial infarction (within one year) or evidence of congestive heart failure.
- Patients with a history of bleeding varices in the prior 3 months.
- Patients who have received any other antitumor treatment (chemotherapy, radiation, immunotherapy) within 4 weeks of study entry or who have not recovered from previous therapy or within 6 weeks for mitomycin C and nitrosureas.
About this study
Official title: Tumor Site Specific Phase I Evaluation of Safety of Hepatic Arterial Infusion of a Matrix-Targeted Retroviral Vector Bearing a Dominant Negative Cyclin G1 Construct as Intervention for Colorectal Carcinoma Metastatic to Liver
This is a Phase I safety study of a gene transfer drug for colorectal cancer that has spread to the liver. The main purpose of this study is to determine if it is safe to give this new intervention to persons with cancer, but we will also look for indications that the drug is effective. Although the findings in animals that have cancer are encouraging, this is the first time humans will receive this experimental gene transfer drug. A gene called cyclin G1 has been shown to play a very important part in cancer growth. In animal experiments, a genetically modified virus (or vector)carrying a modified cyclin G1 gene caused the cancerous tumors to grow much slower or even die. In this safety study, the drug will be injected through the liver artery to get it near the cancer that has spread to the liver. The way the gene gets into the cancer cells is by using a targeted vector that concentrates in the area of the cancer to improve the delivery of the killing gene into cancer cells. The vector we are using is a virus that has been changed so that the infectious genes have been removed and instead carries the modified cyclin G1 gene.
Read the detailed description
Objectives:
- To evaluate the safety/toxicity of hepatic arterial administration of a matrix-targeted retroviral vector bearing a dnG1 construct (Mx-dnG1)
- To evaluate the pharmacodynamics of hepatic arterial infusion of the Mx-dnG1 retroviral vector administered as hepatic arterial infusion.
- To obtain preliminary data on molecular markers of tumor response
- To identify an anti-tumor response to hepatic artery administered Mx-dnG1 retroviral vector
Population: Male and female patients, >18 years old, with metastatic colorectal carcinoma
Sample Size: Nine to fifteen patients (3 to 6 patients treated at each of three dose levels).
Dosage Treatment: Hepatic arterial infusion of the Mx-dnG1 retroviral vector once a day on days 1-5.
Three patients will receive the Mx-dnG1 retroviral vector at Dose Level I. If 1 of 3 patients at Dose Level I develops a grade 3 or 4 adverse event (CTC Version 2.0) which appears to be related or possibly related to the Mx-dnG1 retroviral vector, then 3 additional patients will be enrolled at the same dose level. If at least 2 of the first 3, or 3 of 6, patients at Dose Level I develop a grade 3 to 4 adverse event which appears to be related or possibly related to the Mx-dnG1 retroviral vector, accrual into the study will be held until the data are discussed with the Food and Drug Administration (FDA) and a decision is made whether to continue or terminate study enrollment.
If none of the first 3 or no more than 1 of the first 6 patients that have received vector at Dose Level I develop a grade 3 or 4 adverse event which appears to be related or possibly related to the dnG1 retroviral vector, the dose of the vector will be escalated as follows:
Dose LeveL---No. of Patients---Vector Dose---Maximum Volume
- I----------------3------------3 X 10e9 cfu-------500 ml
- II---------------3------------6 X 10e9 cfu-------500 ml
- III--------------3------------1 X 10e10 cfu------500 ml
The intervention plan will be identical to the one described above for Dose Level I. The Maximum Tolerated Dose (MTD) will be defined as one dose level below the level at which dose limiting toxicity is observed.
Primary Endpoint: Clinical toxicity (DLT and MTD) as defined by patient performance status, toxicity assessment score, hematologic, liver and coagulation profile.
Secondary Endpoint: Obtain preliminary data on molecular markers of tumor response. To assess decrease in tumor size as detected by abdominal CT Scan at 3 and 6 weeks after treatment. Evaluate the pharmacodynamics of hepatic arterial infusion of the Mx-dnG1 retroviral vector administered as hepatic arterial infusion.
- Conditions
- Colorectal Neoplasms
- Being tested
- Mx-dnG1 Retroviral Vector
- Keywords
- Colon cancer, Targeted Injectable Vector, Gene Transfer, Gene Therapy, Retroviral vector
- Medical subject headings
- Colorectal Neoplasms, Colonic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mx-dnG1 Retroviral VectorGenetic
What is being measured
The primary outcome is the main question the study is designed to answer.
dose-limiting toxicity and maximum tolerated dose
Secondary outcomes (1)
objective tumor response by CT scan or MRI
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2002 (estimated)
- Study startNov 2002
- Study completionOct 2003
Why it stopped: Never received final IRB approval for amendments, so never opened officially
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal NeoplasmsStudies of the same condition, open and under way.
- More trials run by University of Southern CaliforniaThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Southern California
- Sponsor type
- University, hospital or other
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00035919
- Sponsor's protocol ID
- 3C-01-2
- Status last verified
- May 2014
- First submitted
- 6 May 2002
- Last updated
- 22 May 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tumor Site Specific Phase I Evaluation of Safety of Hepatic Arterial Infusion of a Matrix-Targeted Retroviral Vector Bearing a Dominant Negative Cyclin G1 Construct as Intervention for Colorectal Carcinoma Metastatic to Liver
- ClinicalTrials.gov ID
- NCT00035919
- Acronym / sponsor ID
- 3C-01-2
- Conditions
- Colorectal Neoplasms
- Keywords
- Colon cancer, Targeted Injectable Vector, Gene Transfer, Gene Therapy, Retroviral vector
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Never received final IRB approval for amendments, so never opened officially
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Southern CaliforniaUniversity, hospital or other
- Study start
- Nov 2002
- Study completion
- Oct 2003
- First posted
- 7 May 2002 (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.
This is a Phase I safety study of a gene transfer drug for colorectal cancer that has spread to the liver. The main purpose of this study is to determine if it is safe to give this new intervention to persons with cancer, but we will also look for indications that the drug is effective. Although the findings in animals that have cancer are encouraging, this is the first time humans will receive this experimental gene transfer drug. A gene called cyclin G1 has been shown to play a very important part in cancer growth. In animal experiments, a genetically modified virus (or vector)carrying a modified cyclin G1 gene caused the cancerous tumors to grow much slower or even die. In this safety study, the drug will be injected through the liver artery to get it near the cancer that has spread to the liver. The way the gene gets into the cancer cells is by using a targeted vector that concentrates in the area of the cancer to improve the delivery of the killing gene into cancer cells. The vector we are using is a virus that has been changed so that the infectious genes have been removed and instead carries the modified cyclin G1 gene.
Detailed description
Objectives:
- To evaluate the safety/toxicity of hepatic arterial administration of a matrix-targeted retroviral vector bearing a dnG1 construct (Mx-dnG1)
- To evaluate the pharmacodynamics of hepatic arterial infusion of the Mx-dnG1 retroviral vector administered as hepatic arterial infusion.
- To obtain preliminary data on molecular markers of tumor response
- To identify an anti-tumor response to hepatic artery administered Mx-dnG1 retroviral vector
Population: Male and female patients, >18 years old, with metastatic colorectal carcinoma
Sample Size: Nine to fifteen patients (3 to 6 patients treated at each of three dose levels).
Dosage Treatment: Hepatic arterial infusion of the Mx-dnG1 retroviral vector once a day on days 1-5.
Three patients will receive the Mx-dnG1 retroviral vector at Dose Level I. If 1 of 3 patients at Dose Level I develops a grade 3 or 4 adverse event (CTC Version 2.0) which appears to be related or possibly related to the Mx-dnG1 retroviral vector, then 3 additional patients will be enrolled at the same dose level. If at least 2 of the first 3, or 3 of 6, patients at Dose Level I develop a grade 3 to 4 adverse event which appears to be related or possibly related to the Mx-dnG1 retroviral vector, accrual into the study will be held until the data are discussed with the Food and Drug Administration (FDA) and a decision is made whether to continue or terminate study enrollment.
If none of the first 3 or no more than 1 of the first 6 patients that have received vector at Dose Level I develop a grade 3 or 4 adverse event which appears to be related or possibly related to the dnG1 retroviral vector, the dose of the vector will be escalated as follows:
Dose LeveL---No. of Patients---Vector Dose---Maximum Volume
- I----------------3------------3 X 10e9 cfu-------500 ml
- II---------------3------------6 X 10e9 cfu-------500 ml
- III--------------3------------1 X 10e10 cfu------500 ml
The intervention plan will be identical to the one described above for Dose Level I. The Maximum Tolerated Dose (MTD) will be defined as one dose level below the level at which dose limiting toxicity is observed.
Primary Endpoint: Clinical toxicity (DLT and MTD) as defined by patient performance status, toxicity assessment score, hematologic, liver and coagulation profile.
Secondary Endpoint: Obtain preliminary data on molecular markers of tumor response. To assess decrease in tumor size as detected by abdominal CT Scan at 3 and 6 weeks after treatment. Evaluate the pharmacodynamics of hepatic arterial infusion of the Mx-dnG1 retroviral vector administered as hepatic arterial infusion.
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
Key inclusion criteria (0 listed)
Key exclusion criteria (7 listed)
- Prior malignancy, except for non-melanoma skin cancer, stage I breast cancer, CIS of cervix from which the patient has been disease free for 5 years.
- Woman who are pregnant or nursing
- Fertile patients unless they agree to use barrier contraception (condoms and spermicide jelly) during the vector infusion period and for six weeks after infusion.
- Patients with medical, psychiatric, or social conditions that would compromise successful adherence to this protocol.
- Patients with indwelling biliary stents or a recent history of cholangitis, hepatitis, presence of disseminated intravascular coagulopathy, or HIV infection. Patients must not have a history of recent myocardial infarction (within one year) or evidence of congestive heart failure.
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 |
|---|---|---|
| Mx-dnG1 Retroviral Vector | Genetic | – |
Primary outcome
dose-limiting toxicity and maximum tolerated dose
1 secondary outcome
objective tumor response by CT scan or MRI
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2014.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Mx-dnG1 Retroviral Vector in people with Colorectal Neoplasms, run by University of Southern California.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 7 exclusion criteria. 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: withdrawn, as of the sponsor's last update on 22 May 2014. Status can change between updates, so confirm with the study contact before making plans.
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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was withdrawn before enrolling participants, so there are no results.
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.
What does the primary outcome measure?
dose-limiting toxicity and maximum tolerated dose. It is what the study was designed to measure, not a finding.
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 22 May 2014.