Metastatic Prostate CancerPhase 1/2NCT01153113
Human Telomerase Reverse Transcriptase Messenger RNA (hTERT mRNA) Transfected Dendritic Cell Vaccines
A Phase 1/2 study testing hTERT mRNA DC in people with Metastatic Prostate Cancer, run by University of Florida.
Trial summary
The purpose of this research is to develop a new and powerful type of immune therapy for prostate cancer patients. This therapy involves vaccinations with special stimulator cells found in the human body called dendritic cells. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Metastatic Prostate Cancer
- What is being tested?
- hTERT mRNA DC
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jan 2008to Dec 2010
- 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
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must have histologically or clinically confirmed adenocarcinoma of the prostate with either:
- metastatic prostate adenocarcinoma, Stage (T1-4, N+, M0) or (T1-4, N0-3, M+) OR
- two documented rising PSA levels while maintained on LHRH analogues.
- Subjects who are receiving nonsteroidal antiandrogen therapy must discontinue therapy for 4 weeks prior to study entry.
- Karnofsky Performance Status (KPS) greater than or equal to 80%
- Age ≥ 18 years
Show all 16Show fewer
- Adequate hematologic function with:
- WBC ≥ 3000 mm3
- hemoglobin ≥ 9 mg/dl
- platelets ≥ 100,000/mm3
- Adequate renal and hepatic function with:
- serum creatinine < 2.5 mg/dl
- bilirubin < 2.0 mg/dl
- Adequate coagulation parameters with:
- Prothrombin Time < 1.5 x control
- Partial thromboplastin time < 1.5 x control • Ability to understand and provide signed inform consent that fulfills Institutional Review Board guidelines.
Who cannot join
- Subjects who have received radiation therapy within 4 weeks of pretreatment evaluation. (There must be at least 12 weeks if prior therapy included 89-Strontium between any prior therapy and study entry.)
- Subjects who have received chemotherapy or biologic regimens within 4 weeks of pretreatment evaluation.
- Subjects who have received immunotherapy within 4 weeks of pretreatment evaluation.
- Subjects who have not recovered from radiation, chemotherapy, or immunotherapy toxicities.
- Subjects with either previously irradiated or new CNS (central nervous system) metastases. (Pre-enrollment head CT is not required.)
- Subjects with a history of autoimmune disease such as, but not restricted to, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis.
Show all 11Show fewer
- Subjects with serious intercurrent chronic or acute illness such as pulmonary (asthma or COPD) or cardiac (NYHA class III or IV) or hepatic disease or other illness considered by the P.I. to constitute an unwarranted high risk for investigational drug treatment.
- Medical or psychological impediment to probable compliance with the protocol.
- Concurrent second malignancy other than non-melanoma skin cancer, or controlled superficial bladder cancer. In the event of prior malignancies treated surgically, the subject must be considered NED (no evidence of disease) for a minimum of 3 years prior to enrollment.
- Presence of an active acute or chronic infection, including symptomatic urinary tract infection, HIV (as determined by ELISA and confirmed by Western Blot) or viral hepatitis (as determined by HBsAg and Hepatitis C serology).
- Subjects on steroid therapy (or other immunosuppressive agents such as azathioprine or cyclosporine A) are excluded on the basis of potential immune suppression. Subjects must have had 4 weeks of discontinuation of any steroid therapy prior to enrollment.
About this study
Official title: Phase II Study of Active Immunotherapy With Mature, Human Telomerase Reverse Transcriptase Messenger RNA -Transfected, Autologous Dendritic Cells (DC) Administered In A Prime-Boost Format to Subjects With Metastatic Prostate Cancer
The purpose of this research is to develop a new and powerful type of immune therapy for prostate cancer patients. This therapy involves vaccinations with special stimulator cells found in the human body called dendritic cells. These dendritic cells can take up proteins released from cancer cells and present pieces of these proteins to immune cells called T lymphocytes to create a strong stimulatory signal to fight the cancer.
One of these proteins is called telomerase, which is found on prostate cancers and is critically important for prostate cancer cells to grow. However, in most cancer patients, the immune system does not adequately destroy the tumor because the T cells are not stimulated sufficiently. T cells require strong stimulation before they grow and become active against cancer cells.
Read more
We have discovered that substances called ribonucleic acids (RNA), which carry the genetic instructions for the production of telomerase, can be used to overcome this problem and stimulate a strong immune response in cancer patients.
In order to test this hypothesis we have designed a clinical study and will enroll patients with metastatic prostate cancer expressing telomerase in order to determine whether or not this vaccine will stimulate T cells, which can recognize and kill prostate tumor cells.
The main objectives of this study are to find out whether injections with dendritic cells grown from blood cells and "pulsed" (mixed together for a short period of time) with RNA derived from the patient's own tumor are:
- Safe without inducing any major side effects.
- And effective in boosting the patient body's immunity against telomerase expressing prostate cancer cells.
- Finally, we will test whether or not tumor shrinkage based on serum PSA levels or on X-ray studies will occur.
We hope that this new form of immune therapy, although in its infancy, will ultimately slow down tumor growth and prolong survival of prostate cancer patients.
Read the detailed description
Primary objectives of trial include to evaluate the safety and biologic efficacy of hTERT mRNA transfected dendritic cells (DC), applied in a prime-boost format, to stimulate hTERT-specific CD4+ and CD8+ T-cell responses in subjects with metastatic prostate cancer. Secondary objectives include estimating objective clinical response, the duration of such responses, progression-free survival and overall survival among all subjects. The hTERT mRNA-transfected DC vaccine platform has previously been studied in several phase I/II trials and has demonstrated safety and bioactivity in subjects with metastatic prostate and renal cell carcinomas. The objective of this trial is to enhance the observed bioactivity of the vaccine by using a prime-boost strategy. This is an open label, uncontrolled safety and efficacy study. Subjects with metastatic prostate cancer will be eligible for this study and will receive 1x107 cells administered ID at study week 1,2,3,4,5, and 6 (Prime). Thereafter, subjects will be randomized with equal probability to receive either 5x106 cells administered ID at study week 10 followed by monthly immunizations (Treatment arm A) or 1x107 cells administered ID at study week 10 followed by monthly immunizations (Treatment arm B). The safety, biologic and clinical efficacy of each regimen will be analyzed. The study will be solely conducted at the University of Florida in Gainesville, FL. Subjects will be recruited through the oncology clinics of the Departments of Urology and Radiation Oncology. The vaccine will be manufactured in a dedicated GMP-compliant cell production facility located on the 4th floor of the Cancer Genetics Research Institute. Immunological testing will be performed in the Immunological Monitoring Core laboratory of the Department of Urology using standardized assay systems. Subjects with histologically or clinically confirmed metastatic prostate cancer (stages pT1-4, N0-3, M+) are eligible for this study. Subjects treated with medical hormone ablative therapy (LHRH analogues or estrogens) should continue to receive LHRH analogues only. In subjects receiving nonsteroidal medical hormonal treatment (i.e. flutamide or bicalutamide) and who are experiencing a rising PSA, a 4 week period of observation will be required following the discontinuation of the nonsteroidal antiandrogen prior to study entry. Subjects will be excluded from study if they have received chemotherapy or other forms of immunotherapy in the 4 weeks prior to study entry. They must not have a history of autoimmune disease, serious intercurrent chronic or acute illness, pulmonary disease, active hepatitis, serologic evidence for HIV, or be receiving corticosteroid or immunosuppressive therapy. All subjects must be older than 18 years. This is a randomized phase II clinical trial, in which up to 36 subjects will be randomized with equal probability to one of the two treatment arms. The objective of this trial is to decide which of the two treatment regimens should be selected for further testing. Hence, the primary objective of this trial is to select the arm with the highest biologic response and the first ranked arm will be selected for further study in a larger efficacy trial.
- Conditions
- Metastatic Prostate Cancer
- Being tested
- hTERT mRNA DC
- Keywords
- adenocarcinoma of the prostate, metastatic prostate adenocarcinoma, Stage (T1-4, N+, M0) or (T1-4, N0-3, M+), rising PSA levels while maintained on LHRH analogues
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hTERT mRNA DCBiological
Subjects receive 1x107 cells per infusion administered ID at study week 1, 2, 3, 4, 5, 6 then receive 5x106 cells per infusion administered ID at study weeks 10, 14, 18, 22, 26, 30, 34, 38, 42, 46 and 50.
hTERT mRNA DCBiological
Subjects receive 1x107 cells per infusion administered ID at study week 1, 2, 3, 4, 5, 6 then receive 1x107 cells per infusion administered ID at study weeks 10, 14, 18, 22, 26, 30, 34, 38, 42, 46 and 50.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm A | Experimental | • 5x106 cells per infusion administered ID Receives: Biological: hTERT mRNA DC |
| Treatment Arm B | Experimental | • 1x107 cells per infusion administered ID (Treatment arm B). Receives: Biological: hTERT mRNA DC |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary objective of this trial is to evaluate the safety of a boosting regimen using immunizations with two distinct doses of hTERT mRNA DC.
All subjects will receive 1x107 cells administered ID at study weeks 1, 2, 3, 4, 5, and 6. Subjects will subsequently be randomized with equal probability to receive hTERT mRNA DC at study weeks 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, and 50 at one of the following doses:
- 5x106 cells per infusion administered ID (Treatment arm A).
- 1x107 cells per infusion administered ID (Treatment arm B).
Measured: 50 Weeks
Secondary outcomes (3)
PSA-specific T cells from pre- and post-therapy PBMC samples
To analyze the induction of PSA-specific T cells from pre- and post-therapy PBMC samples among subjects enrolled in both treatment arms.
Measured: 50 Weeks
Calculate progression-free survival if subject responds to therapy.
To monitor eventual clinical responses as evidenced on clinical response criteria and calculate progression-free survival if subject responds to therapy.
Measured: 50 Weeks
overall survival
To determine overall survival for all subjects at one-year of follow-up.
Measured: 50 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2010 (estimated)
- Study startJan 2008
- Primary completionDec 2009 (estimated)
- Study completionDec 2010 (estimated)
Why it stopped: IND has been withdrawn and the study is closed.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Prostate CancerStudies of the same condition, open and under way.
- More trials run by University of FloridaThe 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
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01153113
- Sponsor's protocol ID
- LAMP hTERT DC Vaccine
- Status last verified
- Feb 2011
- First submitted
- 31 Mar 2010
- Last updated
- 2 Dec 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Active Immunotherapy With Mature, Human Telomerase Reverse Transcriptase Messenger RNA -Transfected, Autologous Dendritic Cells (DC) Administered In A Prime-Boost Format to Subjects With Metastatic Prostate Cancer
- ClinicalTrials.gov ID
- NCT01153113
- Acronym / sponsor ID
- LAMP hTERT DC Vaccine
- Conditions
- Metastatic Prostate Cancer
- Keywords
- adenocarcinoma of the prostate, metastatic prostate adenocarcinoma, Stage (T1-4, N+, M0) or (T1-4, N0-3, M+), rising PSA levels while maintained on LHRH analogues
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: IND has been withdrawn and the study is closed.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Study start
- Jan 2008
- Primary completion
- Dec 2009 (estimated)
- Study completion
- Dec 2010 (estimated)
- First posted
- 29 Jun 2010 (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.
The purpose of this research is to develop a new and powerful type of immune therapy for prostate cancer patients. This therapy involves vaccinations with special stimulator cells found in the human body called dendritic cells. These dendritic cells can take up proteins released from cancer cells and present pieces of these proteins to immune cells called T lymphocytes to create a strong stimulatory signal to fight the cancer.
One of these proteins is called telomerase, which is found on prostate cancers and is critically important for prostate cancer cells to grow. However, in most cancer patients, the immune system does not adequately destroy the tumor because the T cells are not stimulated sufficiently. T cells require strong stimulation before they grow and become active against cancer cells.
We have discovered that substances called ribonucleic acids (RNA), which carry the genetic instructions for the production of telomerase, can be used to overcome this problem and stimulate a strong immune response in cancer patients.
In order to test this hypothesis we have designed a clinical study and will enroll patients with metastatic prostate cancer expressing telomerase in order to determine whether or not this vaccine will stimulate T cells, which can recognize and kill prostate tumor cells.
The main objectives of this study are to find out whether injections with dendritic cells grown from blood cells and "pulsed" (mixed together for a short period of time) with RNA derived from the patient's own tumor are:
- Safe without inducing any major side effects.
- And effective in boosting the patient body's immunity against telomerase expressing prostate cancer cells.
- Finally, we will test whether or not tumor shrinkage based on serum PSA levels or on X-ray studies will occur.
We hope that this new form of immune therapy, although in its infancy, will ultimately slow down tumor growth and prolong survival of prostate cancer patients.
Detailed description
Primary objectives of trial include to evaluate the safety and biologic efficacy of hTERT mRNA transfected dendritic cells (DC), applied in a prime-boost format, to stimulate hTERT-specific CD4+ and CD8+ T-cell responses in subjects with metastatic prostate cancer. Secondary objectives include estimating objective clinical response, the duration of such responses, progression-free survival and overall survival among all subjects. The hTERT mRNA-transfected DC vaccine platform has previously been studied in several phase I/II trials and has demonstrated safety and bioactivity in subjects with metastatic prostate and renal cell carcinomas. The objective of this trial is to enhance the observed bioactivity of the vaccine by using a prime-boost strategy. This is an open label, uncontrolled safety and efficacy study. Subjects with metastatic prostate cancer will be eligible for this study and will receive 1x107 cells administered ID at study week 1,2,3,4,5, and 6 (Prime). Thereafter, subjects will be randomized with equal probability to receive either 5x106 cells administered ID at study week 10 followed by monthly immunizations (Treatment arm A) or 1x107 cells administered ID at study week 10 followed by monthly immunizations (Treatment arm B). The safety, biologic and clinical efficacy of each regimen will be analyzed. The study will be solely conducted at the University of Florida in Gainesville, FL. Subjects will be recruited through the oncology clinics of the Departments of Urology and Radiation Oncology. The vaccine will be manufactured in a dedicated GMP-compliant cell production facility located on the 4th floor of the Cancer Genetics Research Institute. Immunological testing will be performed in the Immunological Monitoring Core laboratory of the Department of Urology using standardized assay systems. Subjects with histologically or clinically confirmed metastatic prostate cancer (stages pT1-4, N0-3, M+) are eligible for this study. Subjects treated with medical hormone ablative therapy (LHRH analogues or estrogens) should continue to receive LHRH analogues only. In subjects receiving nonsteroidal medical hormonal treatment (i.e. flutamide or bicalutamide) and who are experiencing a rising PSA, a 4 week period of observation will be required following the discontinuation of the nonsteroidal antiandrogen prior to study entry. Subjects will be excluded from study if they have received chemotherapy or other forms of immunotherapy in the 4 weeks prior to study entry. They must not have a history of autoimmune disease, serious intercurrent chronic or acute illness, pulmonary disease, active hepatitis, serologic evidence for HIV, or be receiving corticosteroid or immunosuppressive therapy. All subjects must be older than 18 years. This is a randomized phase II clinical trial, in which up to 36 subjects will be randomized with equal probability to one of the two treatment arms. The objective of this trial is to decide which of the two treatment regimens should be selected for further testing. Hence, the primary objective of this trial is to select the arm with the highest biologic response and the first ranked arm will be selected for further study in a larger efficacy trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm A | Experimental | Biological: hTERT mRNA DC• 5x106 cells per infusion administered ID |
| Treatment Arm B | Experimental | Biological: hTERT mRNA DC• 1x107 cells per infusion administered ID (Treatment arm B). |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Subjects must have histologically or clinically confirmed adenocarcinoma of the prostate with either:
- metastatic prostate adenocarcinoma, Stage (T1-4, N+, M0) or (T1-4, N0-3, M+) OR
- two documented rising PSA levels while maintained on LHRH analogues.
- WBC ≥ 3000 mm3
- hemoglobin ≥ 9 mg/dl
Key exclusion criteria (11 listed)
- Subjects who have received radiation therapy within 4 weeks of pretreatment evaluation. (There must be at least 12 weeks if prior therapy included 89-Strontium between any prior therapy and study entry.)
- Subjects who have received chemotherapy or biologic regimens within 4 weeks of pretreatment evaluation.
- Subjects who have received immunotherapy within 4 weeks of pretreatment evaluation.
- Subjects who have not recovered from radiation, chemotherapy, or immunotherapy toxicities.
- Subjects with either previously irradiated or new CNS (central nervous system) metastases. (Pre-enrollment head CT is not required.)
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 |
|---|---|---|
| hTERT mRNA DCSubjects receive 1x107 cells per infusion administered ID at study week 1, 2, 3, 4, 5, 6 then receive 5x106 cells per infusion administered ID at study weeks 10, 14, 18, 22, 26, 30, 34, 38, 42, 46 and 50. | Biological | Treatment Arm A |
| hTERT mRNA DCSubjects receive 1x107 cells per infusion administered ID at study week 1, 2, 3, 4, 5, 6 then receive 1x107 cells per infusion administered ID at study weeks 10, 14, 18, 22, 26, 30, 34, 38, 42, 46 and 50. | Biological | Treatment Arm B |
Primary outcome
The primary objective of this trial is to evaluate the safety of a boosting regimen using immunizations with two distinct doses of hTERT mRNA DC.
Time frame: 50 Weeks
All subjects will receive 1x107 cells administered ID at study weeks 1, 2, 3, 4, 5, and 6. Subjects will subsequently be randomized with equal probability to receive hTERT mRNA DC at study weeks 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, and 50 at one of the following doses: * 5x106 cells per infusion administered ID (Treatment arm A). * 1x107 cells per infusion administered ID (Treatment arm B).
3 secondary outcomes
PSA-specific T cells from pre- and post-therapy PBMC samples
Time frame: 50 Weeks
Calculate progression-free survival if subject responds to therapy.
Time frame: 50 Weeks
overall survival
Time frame: 50 Weeks
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 2 Dec 2011.
Related trials for Metastatic Prostate Cancer
RecruitingPhase 1
A Study of [225Ac]Ac-AKY-2519 in Patients With Metastatic Castration-Resistant Prostate Cancer
Castration Resistant Metastatic Prostate Cancer, Prostate Cancer
Active, not recruitingEarly Phase 1
Androgen Receptor Signaling and Prostate-Specific Membrane Antigen Expression
Prostate Adenocarcinoma, Prostate Cancer
RecruitingPhase 2
Estrogen to Improve Quality of Life for Men With Newly Diagnosed or Recurrent Metastatic Hormone Sensitive Prostate Cancer, EQUIP Trial
Castration-Sensitive Prostate Adenocarcinoma, Metastatic Castration-Sensitive Prostate Adenocarcinoma
RecruitingPhase 1/2
A Trial to Find Out if REGN5678 (Nezastomig) is Safe and How Well it Works Alone or in Combination With Cemiplimab for Adult Participants With Metastatic Castration-Resistant Prostate Cancer and Other Tumors
Metastatic Castration-Resistant Prostate Cancer (mCRPC), Clear Cell Renal Cell Carcinoma (ccRCC)
RecruitingPhase 1
A Study of [225Ac]Ac-AKY-2519 in Patients With B7-H3 Expressing Solid Tumors
NSCLC, NSCLC (Advanced Non-small Cell Lung Cancer)
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 hTERT mRNA DC in people with Metastatic Prostate Cancer, run by University of Florida.
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 16 inclusion and 11 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 2 Dec 2011. 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?
The primary objective of this trial is to evaluate the safety of a boosting regimen using immunizations with two distinct doses of hTERT mRNA DC. (time frame: 50 Weeks). 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 Dec 2011.