Carcinoma, Advanced MetastaticPhase 1Auto TAGNCT00684294
Phase I Trial of TGFB2-Antisense-GMCSF Gene Modified Autologous Tumor Cell (TAG) Vaccine for Advanced Cancer
A Phase 1 study testing TGFβ2 Antisense-GMCSF Gene Modified Autologous Tumor Cell (TAG) Vaccine in people with Carcinoma, Advanced Metastatic, run by Mary Crowley Medical Research Center at 1 site in United States.
Trial summary
Preliminary studies with a variety of vaccines suggest target accessibility (potential immunogenicity) in a variety of solid tumors to immune directed approaches. However, four primary factors limit the generation of effective immune mediated anticancer activity in therapeutic application: 1. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Advanced Metastatic
- What is being tested?
- TGFβ2 Antisense-GMCSF Gene Modified Autologous Tumor Cell (TAG) Vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 1 siteUnited States
- Study dates
- 27 May 2008to 28 May 2019
- 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
Who may be able to join
- Histologically confirmed advanced or metastatic non-curable solid tumor (if limited to a single lesion and not a candidate for curative surgery or radiation therapy).
- Completed ≥1 conventional therapy.
- Clinically indicated surgery or procedure to collect available tumor in sufficient quantity ("golf ball size," pleural or ascites fluid may also be collected) for vaccine processing.
- Subjects that have completed all acceptable therapies that are the current standard of care for their respective diseases.
- Recovered from all toxicities related to prior therapies.
- Subjects with brain metastases treated at least ≥2 months prior to enrollment, without related clinical symptoms and must have a stable neurological exam on the screening evaluation.
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- ≥1 measurable or evaluable lesion.
- Age ≥18 years.
- ECOG performance status (PS) 0-1.
- Normal organ and marrow function:
- Absolute granulocyte count: ≥1,500/mm3
- Platelets: ≥100,000/mm3
- Total bilirubin: ≤2 mg/dL
- AST(SGOT)/ALT(SGPT): ≤2x institutional upper limit of normal
- Creatinine: <1.5 mg/dL
- Ability to understand and the willingness to sign a written informed consent document.
- Negative pregnancy test.
Who cannot join
- Surgery involving general anesthesia, chemotherapy, radiotherapy, steroid therapy, or immunotherapy within 4 weeks prior to entering the study.
- Patient must not have received any other investigational agents within 30 days prior to study entry.
- Patients with known brain metastases unless treated and stable for ≥2 months.
- Patients with mucinous adenocarcinoma.
- Short term (<30 days) concurrent systemic steroids ≤ 0.125 mg/kg prednisone per day (maximum 10 mg/day) and bronchodilators (inhaled steroids) are permitted; other steroid regimens and/or immunosuppressives are excluded. Patients requiring steroids following previous CNS radiation for metastatic disease are excluded.
- Prior splenectomy.
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- Prior malignancy (excluding nonmelanoma carcinomas of the skin) unless in remission for ≥2 years.
- Kaposi's Sarcoma.
- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients who are pregnant or nursing.
- Patients who are HIV positive.
- Patients with chronic Hepatitis B and C infection.
- Patients with a history of autoimmune diseases.
Trial locations and contacts
1 site in 1 country.
United States1 site
Mary Crowley Cancer Research Centers
Dallas, Texas, 75230
About this study
Preliminary studies with a variety of vaccines suggest target accessibility (potential immunogenicity) in a variety of solid tumors to immune directed approaches. However, four primary factors limit the generation of effective immune mediated anticancer activity in therapeutic application:
- identifying and/or targeting cancer associated immunogen(s) in an individual patient
- insufficient or inhibited level of antigen presenting cell priming and/or presentation
- suboptimal T cell activation and proliferation
- cancer-induced inhibition of the anticancer immune response in both afferent and efferent limbs.
In an effort to overcome these limitations, we have designed a novel autologous vaccine to address inability to fully identify cancer associated antigens, antigen recognition by the immune system (i.e. antigen to immunogen), effector potency, and cancer-induced resistance. We have completed clinical investigations using two different gene vaccine approaches to induce enhancement of tumor antigen recognition which have demonstrated therapeutic efficacy. Specifically, both the use of a GMCSF gene transduced vaccine and a TGFβ2 antisense gene vaccine, in separate trials, have demonstrated similar beneficial effects without any evidence of significant toxicity in advanced cancer patients. The GMCSF transgene directly stimulates increased expression of tumor antigen(s) and enhances dendritic cell migration to the vaccination site. TGFβ2 blockade following intracellular TGFβ2 antisense gene expression reduces production of immune inhibiting activity at the vaccine site. These agents have never been used in combination but the rationale of integrating enhancement of an anticancer immune response concurrently with a reduction in cancer-induced immune suppression is conceptually sound. We will harvest autologous cancer cells from patients with advanced refractory cancer. We have constructed a TGFβ2 antisense / GMCSF expression vector plasmid and have successfully demonstrated preclinical activity of the vector function following transfection by electroporation and irradiation of autologous cancer tissue.
- Conditions
- Carcinoma, Advanced Metastatic
- Being tested
- TGFβ2 Antisense-GMCSF Gene Modified Autologous Tumor Cell (TAG) Vaccine
- Keywords
- cancer, oncology, solid tumor
- Medical subject headings
- Carcinoma, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TGFβ2 Antisense-GMCSF Gene Modified Autologous Tumor Cell (TAG) VaccineBiological
Patients with solid tumors will receive TAG Vaccine 1 x 10^7 cells/ injection or TAG Vaccine 2.5 X 10^7 cells/injection once a month for up to 12 doses via intradermal injection as long as sufficient material is available. Selection of cohort is dependent on the amount of tumor cell yield following harvest and processing.
| Study group | Role | What they receive |
|---|---|---|
| TAG Vaccine 1 x 10^7 cells/ injection | Experimental | TAG Vaccine 1 x 10^7 cells/injection Receives: Biological: TGFβ2 Antisense-GMCSF Gene Modified Autologous Tumor Cell (TAG) Vaccine |
| TAG Vaccine 2.5 X 10^7 cells/injection | Experimental | TAG Vaccine 2.5 X 10^7 cells/injection Receives: Biological: TGFβ2 Antisense-GMCSF Gene Modified Autologous Tumor Cell (TAG) Vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine safety following the administration of TAG vaccine in advanced solid tumor patients who have no acceptable form of standard therapy.
Measured: 6 months
Secondary outcomes (2)
To determine the time to progression following the administration of TAG vaccine.
Measured: survival
To evaluate the effect on immune stimulation.
Measured: baseline, Month 3, and Month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2008 (estimated)
- Study start27 May 2008
- Primary completionMay 2009
- Study completion28 May 2019
Why it stopped: Since no safety issues have been reported to date in association with TAG vaccine, no further survival follow-up will be done.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, Advanced MetastaticStudies 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mary Crowley Medical Research Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Minal Barve, MD, Principal investigator, Mary Crowley Cancer Research Centers
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00684294
- Sponsor's protocol ID
- MCMRC #08-08
- Acronym
- Auto TAG
- Status last verified
- Feb 2020
- First submitted
- 21 May 2008
- Last updated
- 2 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of TGFB2-Antisense-GMCSF Gene Modified Autologous Tumor Cell (TAG) Vaccine for Advanced Cancer
- ClinicalTrials.gov ID
- NCT00684294
- Acronym / sponsor ID
- Auto TAG / MCMRC #08-08
- Conditions
- Carcinoma, Advanced Metastatic
- Keywords
- cancer, oncology, solid tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Since no safety issues have been reported to date in association with TAG vaccine, no further survival follow-up will be done.
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Mary Crowley Medical Research CenterUniversity, hospital or other
- Study start
- 27 May 2008 (actual)
- Primary completion
- May 2009 (actual)
- Study completion
- 28 May 2019 (actual)
- First posted
- 26 May 2008 (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.
Preliminary studies with a variety of vaccines suggest target accessibility (potential immunogenicity) in a variety of solid tumors to immune directed approaches. However, four primary factors limit the generation of effective immune mediated anticancer activity in therapeutic application:
- identifying and/or targeting cancer associated immunogen(s) in an individual patient
- insufficient or inhibited level of antigen presenting cell priming and/or presentation
- suboptimal T cell activation and proliferation
- cancer-induced inhibition of the anticancer immune response in both afferent and efferent limbs.
In an effort to overcome these limitations, we have designed a novel autologous vaccine to address inability to fully identify cancer associated antigens, antigen recognition by the immune system (i.e. antigen to immunogen), effector potency, and cancer-induced resistance. We have completed clinical investigations using two different gene vaccine approaches to induce enhancement of tumor antigen recognition which have demonstrated therapeutic efficacy. Specifically, both the use of a GMCSF gene transduced vaccine and a TGFβ2 antisense gene vaccine, in separate trials, have demonstrated similar beneficial effects without any evidence of significant toxicity in advanced cancer patients. The GMCSF transgene directly stimulates increased expression of tumor antigen(s) and enhances dendritic cell migration to the vaccination site. TGFβ2 blockade following intracellular TGFβ2 antisense gene expression reduces production of immune inhibiting activity at the vaccine site. These agents have never been used in combination but the rationale of integrating enhancement of an anticancer immune response concurrently with a reduction in cancer-induced immune suppression is conceptually sound. We will harvest autologous cancer cells from patients with advanced refractory cancer. We have constructed a TGFβ2 antisense / GMCSF expression vector plasmid and have successfully demonstrated preclinical activity of the vector function following transfection by electroporation and irradiation of autologous cancer tissue.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TAG Vaccine 1 x 10^7 cells/ injection | Experimental | Biological: TGFβ2 Antisense-GMCSF Gene Modified Autologous Tumor Cell (TAG) VaccineTAG Vaccine 1 x 10^7 cells/injection |
| TAG Vaccine 2.5 X 10^7 cells/injection | Experimental | Biological: TGFβ2 Antisense-GMCSF Gene Modified Autologous Tumor Cell (TAG) VaccineTAG Vaccine 2.5 X 10^7 cells/injection |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Histologically confirmed advanced or metastatic non-curable solid tumor (if limited to a single lesion and not a candidate for curative surgery or radiation therapy).
- Completed ≥1 conventional therapy.
- Clinically indicated surgery or procedure to collect available tumor in sufficient quantity ("golf ball size," pleural or ascites fluid may also be collected) for vaccine processing.
- Subjects that have completed all acceptable therapies that are the current standard of care for their respective diseases.
- Recovered from all toxicities related to prior therapies.
Key exclusion criteria (13 listed)
- Surgery involving general anesthesia, chemotherapy, radiotherapy, steroid therapy, or immunotherapy within 4 weeks prior to entering the study.
- Patient must not have received any other investigational agents within 30 days prior to study entry.
- Patients with known brain metastases unless treated and stable for ≥2 months.
- Patients with mucinous adenocarcinoma.
- Short term (<30 days) concurrent systemic steroids ≤ 0.125 mg/kg prednisone per day (maximum 10 mg/day) and bronchodilators (inhaled steroids) are permitted; other steroid regimens and/or immunosuppressives are excluded. Patients requiring steroids following previous CNS radiation for metastatic disease are excluded.
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 |
|---|---|---|
| TGFβ2 Antisense-GMCSF Gene Modified Autologous Tumor Cell (TAG) VaccinePatients with solid tumors will receive TAG Vaccine 1 x 10^7 cells/ injection or TAG Vaccine 2.5 X 10^7 cells/injection once a month for up to 12 doses via intradermal injection as long as sufficient material is available. Selection of cohort is dependent on the amount of tumor cell yield following harvest and processing. | Biological | TAG Vaccine 1 x 10^7 cells/ injection, TAG Vaccine 2.5 X 10^7 cells/injection |
Primary outcome
To determine safety following the administration of TAG vaccine in advanced solid tumor patients who have no acceptable form of standard therapy.
Time frame: 6 months
2 secondary outcomes
To determine the time to progression following the administration of TAG vaccine.
Time frame: survival
To evaluate the effect on immune stimulation.
Time frame: baseline, Month 3, and Month 6
Results and safety
The study was stopped early (reason given: Since no safety issues have been reported to date in association with TAG vaccine, no further survival follow-up will be done.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2020.
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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.
Minal Barve, MD principal investigator
Mary Crowley Cancer Research Centers
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TGFβ2 Antisense-GMCSF Gene Modified Autologous Tumor Cell (TAG) Vaccine in people with Carcinoma, Advanced Metastatic, run by Mary Crowley Medical Research Center at 1 site 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?
The sponsor lists 17 inclusion and 13 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: stopped early, as of the sponsor's last update on 2 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 was stopped early (reason given: Since no safety issues have been reported to date in association with TAG vaccine, no further survival follow-up will be done.). Results are not available in the source record.
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?
To determine safety following the administration of TAG vaccine in advanced solid tumor patients who have no acceptable form of standard therapy. (time frame: 6 months). 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 2 Mar 2020.