Prostate CancerPhase 1/2CRITICALNCT00753220
Safety Study of Autologous Dendritic Cells Injected Into the Prostate After Cryoablation for Advanced Prostate Cancer
A Phase 1/2 study testing VDC2008 and Cyclophosphamide in people with Prostate Cancer, run by Bostwick Laboratories at 1 site in United States.
Trial summary
The purpose of this study is to determine if the intra-tumoral injection of a subject's own dendritic cells after cryotherapy of the prostate is a safe and effective treatment for advanced prostate cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- VDC2008 and Cyclophosphamide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2009to Dec 2011
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Men ≥ 18 years of age and any race.
- Signed Informed Consent document obtained prior to the initiation of screening procedures.
- Histologically documented primary adenocarcinoma of the prostate. A specimen of the primary tumor must be submitted to the Central Pathology Laboratory for confirmation of prostatic adenocarcinoma and determination of Gleason Sum grading.
- Prior history of:
- Androgen Deprivation Therapy; or
- Organ-preserving therapy (i.e., non-prostatectomy) for primary prostate cancer (e.g., radiation therapy).
Show all 34Show fewer
- In case of recurrence, subject must have evidence of prostate cancer by a positive biopsy revealing adenocarcinoma within the past 6 months of screening and confirmed by the Central Pathology Laboratory.
- TxNxM1a and/or TxNxM1b disease limited to three total metastatic sites as evidenced by lymph node metastases and /or bone metastases at time of screening.
- TxNxM1a : Lymph node metastases histologically proven and confirmed by Central Pathology Laboratory;
- TxNxM1a: Lymph node metastases not histologically proven, given that the following are satisfied in the temporal order listed:
- Computed tomography (CT) or Magnetic Resonance Imaging (MRI) for positive lymph nodes negative at original diagnosis of prostate cancer;
- Definitive local treatment undertaken;
- Evidence of local treatment failure on the basis of rising serum PSA;
- Prostatic biopsy positive for carcinoma;
- Subsequent CT or MRI reveals lymph node(s) of 2 cm diameter or greater
- TxNxM1b: Bone metastases demonstrated by radionuclide bone scan, CT, or MRI.
- Androgen-independent prostate cancer as defined by:
- Three consecutive rises of at least 10% each in serum PSA, in which all serum PSA measurements are separated by at least one week and results are obtained within 60 days of study screening; OR
- Three rises that involve an increase of 50% over the nadir serum PSA, in which all serum PSA measurements are separated by at least one week and results are obtained within 60 days of study screening;
- A castrate level of testosterone (<50 ng/dl) obtained within 60 days of study screening.
- Life expectancy of greater than or equal to 12 months.
- Adequate hematological function as defined by:
- Total WBC > 4,500/mm3
- Total lymphocyte count > 500/mm3
- Hemoglobin > 12.0 g/dl
- Neutrophils > 1,500/mm3
- Platelets > 150,000/mm3
- Adequate renal function with creatinine < 2.0 mg/dl.
- Adequate liver function as defined by:
- AST and ALT < 2 times the upper limit of normal;
- Serum bilirubin < 2.0 mg/dl;
- Alkaline Phosphatase < 2.0 upper limit of normal.
- Assessment of superficial veins as adequate for the performance of leukapheresis.
- No active major medical or psychological problems that could be complicated by study participation.
Who cannot join
- The presence of lung, liver or brain metastases, malignant pleural effusions or malignant ascites.
- Moderate or severe symptomatic metastatic disease. Subjects who meet either of the following criteria must be excluded:
- A requirement for treatment with opioid analgesics for any reason within 21 days prior to study screening;
- Average weekly pain score of 4 or more as reported on the 11-point Pain Intensity - Numerical Rating Scale (Appendix III) over the two weeks prior to study enrollment.
- Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2 accessed at study screening visit.
- Chemotherapy treatment at any time prior to study screening.
Show all 30Show fewer
- Radiation therapy for metastatic disease, including intravenous radioactive strontium therapy.
- Initiation or discontinuation of bisphosphonate therapy within 28 days prior to study screening. Subjects taking bisphosphonate medication must not have their dosing regimen altered until objective disease progression is independently confirmed.
- Treatment with any of the following medications or interventions within 28 days of study screening:
- Systemic corticosteroids (use of inhaled, intranasal and topical steroids is acceptable);
- External beam radiation therapy or surgery;
- PC-SPES (or PC-SPEC) or Saw Palmetto extract;
- Megestrol acetate (Megace®), diethyl stilbesterol (DES), or cyproterone acetate;
- Ketoconazole;
- High dose calcitriol (i.e., > 7.0 μg/week);
- Any other systemic therapy for prostate cancer.
- Treatment with any investigational vaccine within 2 years of enrollment to this study.
- Treatment with any other investigational product within 28 days of study screening.
- Pathologic long-bone fractures, imminent pathologic long-bone fracture (cortical erosion on radiography > 50%) or spinal cord compression.
- Impending untreated spinal cord compression or urinary outlet obstruction.
- Paget's Disease of bone.
- History of stage III or greater cancer, excluding prostate cancer:
- Basal or squamous cell skin cancers must have been adequately treated and the subject must be disease-free at the time of study screening visit;
- Subjects with a history of stage I or II cancer must have been adequately treated and be disease-free for ≥ 3 years at the time of study screening
- Requirement for systemic immunosuppressive therapy for any reason
- Prior or currently active autoimmune disease requiring management with systemic immunosuppression. Such conditions include inflammatory bowel disease, systemic vasculitis, scleroderma, psoriasis, multiple sclerosis, hemolytic anemia, immune-related thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, sarcoidosis, or other rheumatological disease.
- Any infection requiring parenteral antibiotic therapy or causing fever (body temperature > 100.5°F or 38.1°C) within 1 week prior to study screening.
- Known allergy, intolerance, or medical contraindication to receiving the contrast dye required for the protocol-specified CT imaging
- History of asthma, anaphylaxis, or other known serious adverse reactions to vaccines.
- Any medical intervention or other condition which, in the opinion of the Physician-Investigator could compromise adherence with study requirements or otherwise compromise study subject safety and the study's objectives.
Trial locations and contacts
1 site in 1 country.
United States1 site
Community Memorial Hospital
Ventura, California, 93003
About this study
Official title: A Phase I/IIa Trial of Combined Cryotherapy and Intra-tumoral Immunotherapy With Autologous Immature Dendritic Cells (VDC2008) in Chemo-naïve Men With Prostatic Adenocarcinoma and Limited Metastases to Lymph Nodes and/or Bone
The purpose of this study is to determine if the intra-tumoral injection of a subject's own dendritic cells after cryotherapy of the prostate is a safe and effective treatment for advanced prostate cancer.
In theory, the injected dendritic cells will internalize antigens from the tumor cells which have been damaged by cryotherapy and activate the subject's immune system against that specific tumor.
Read more
Subjects will also receive a low dose chemotherapy designed to lower the number of T-regulatory cells which have been shown to lower or stop some immune system responses.
Hypothesis 1: Dendritic cell injection into cryotreated prostate cancer is non-toxic;
Hypothesis 2: Dendritic cell injection into cryotreated prostate cancer is medically beneficial to the subject.
Read the detailed description
The study treatment dendritic cells (VDC2008) will be injected into the prostate following prostatic cryoablation. It is speculated that antigen from the cryoablated cancer will be available in the vicinity of the cryoablation field immediately following the procedure. Autologous, immature dendritic cells are capable of internalizing antigen, migrating to the lymphatic system, and presenting antigenic epitopes to T lymphocytes. In this way, dendritic cells are capable of initiating a cell-mediated systemic immune response.
In concept, the cancer itself should provide a specific and potentially broad spectrum of cancer-related antigens. Regulatory T lymphocytes, which have been implicated in dampening or halting cell-mediated, antigen-specific immune responses, will be selectively depleted using a regimen of low-dose cyclophosphamide. Low-dose cyclophosphamide has been empirically shown to selectively deplete the number of circulating regulatory T cells.
Using this combination of therapies, it is thought that a clinically significant anti-cancer immune response might be elicited.
- Conditions
- Prostate Cancer
- Being tested
- VDC2008, Cyclophosphamide
- Keywords
- Metastatic, Androgen, Independent, Prostate Cancer, (AIPC),, Hormone-refractory, (HRPC),, cryotherapy,, dendritic cell,, immunotherapy, Chemo-naïve, lymph nodes, bone
- Medical subject headings
- Prostatic Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VDC2008Biological
Also called Autologous dendritic cells
Intratumoral injection of VDC2008 post-cryotherapy.
Dosage will depend on cohort: 2.5 x 10^7, 7.5 x 10^7 or 1.0 x 10^8 cells
CyclophosphamideDrug
Cyclophosphamide i.v. given at day -3 (dose: 300mg/m2); Low-dose Cyclophosphamide pill given twice daily (dose: 25 mg, p.o., b.i.d. for 7 days on and 7 days off; a total of 6 cycles [1 cycle = 4 weeks] starting Week 2 after cryoablation and going to Week 26)
| Study group | Role | What they receive |
|---|---|---|
| VDC2008 | Experimental | Cryoablation of prostate followed by dendritic cell injection (dose of 2.5 x 10^7, 7.5 x 10^7, or 1.0 x 10^8 cells depending on assigned cohort) into prostate and low dose cyclophosphamide therapy (dose: 25 mg, p.o., b.i.d. for 7 days on and 7 days off; a total of 6 cycles [1 cycle = 4 weeks] starting Week 2 after cryoablation and going to Week 26) Receives: Biological: VDC2008; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
PROTOCOL EXCERPT: The primary objective of the Phase I Portion of this study is the determination of the maximum tolerated dose (MTD) of intratumorally injected study agent VDC2008 administered following cryoablation of the prostate, and pre- and post-treatment with a low-dose cyclophosphamide therapy, as determined by toxicity and adverse event monitoring following treatment of metastatic androgen-independent prostate cancer.
ADDITIONAL INFORMATION: MTD was not reached by any study participant prior to end of the study. Additional participants would have been necessary to determine MTD.
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2008 (estimated)
- Study startAug 2009
- Primary completionMay 2011
- Study completionDec 2011
Why it stopped: Withdrew the IND with the FDA.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Prostate CancerStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bostwick Laboratories
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Prostate Institute of America, Community Memorial HealthCenter, HemaCare Corporation
- Responsible party
- Sponsor
- Investigators
- Duke K Bahn, M.D., Principal investigator, Prostate Institue of America
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00753220
- Sponsor's protocol ID
- CRITICAL001
- Acronym
- CRITICAL
- Status last verified
- Nov 2014
- First submitted
- 12 Sep 2008
- Last updated
- 4 Nov 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/IIa Trial of Combined Cryotherapy and Intra-tumoral Immunotherapy With Autologous Immature Dendritic Cells (VDC2008) in Chemo-naïve Men With Prostatic Adenocarcinoma and Limited Metastases to Lymph Nodes and/or Bone
- ClinicalTrials.gov ID
- NCT00753220
- Acronym / sponsor ID
- CRITICAL / CRITICAL001
- Conditions
- Prostate Cancer
- Keywords
- Metastatic, Androgen, Independent, Prostate Cancer, (AIPC),, Hormone-refractory, (HRPC),, cryotherapy,
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Withdrew the IND with the FDA.
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Bostwick LaboratoriesIndustry (pharma, biotech, devices)
- Collaborators
- Prostate Institute of America, Community Memorial HealthCenter, HemaCare Corporation
- Study start
- Aug 2009
- Primary completion
- May 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 16 Sep 2008 (estimated)
- Results
- Posted 4 Nov 2014
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 study is to determine if the intra-tumoral injection of a subject's own dendritic cells after cryotherapy of the prostate is a safe and effective treatment for advanced prostate cancer.
In theory, the injected dendritic cells will internalize antigens from the tumor cells which have been damaged by cryotherapy and activate the subject's immune system against that specific tumor.
Subjects will also receive a low dose chemotherapy designed to lower the number of T-regulatory cells which have been shown to lower or stop some immune system responses.
Hypothesis 1: Dendritic cell injection into cryotreated prostate cancer is non-toxic;
Hypothesis 2: Dendritic cell injection into cryotreated prostate cancer is medically beneficial to the subject.
Detailed description
The study treatment dendritic cells (VDC2008) will be injected into the prostate following prostatic cryoablation. It is speculated that antigen from the cryoablated cancer will be available in the vicinity of the cryoablation field immediately following the procedure. Autologous, immature dendritic cells are capable of internalizing antigen, migrating to the lymphatic system, and presenting antigenic epitopes to T lymphocytes. In this way, dendritic cells are capable of initiating a cell-mediated systemic immune response.
In concept, the cancer itself should provide a specific and potentially broad spectrum of cancer-related antigens. Regulatory T lymphocytes, which have been implicated in dampening or halting cell-mediated, antigen-specific immune responses, will be selectively depleted using a regimen of low-dose cyclophosphamide. Low-dose cyclophosphamide has been empirically shown to selectively deplete the number of circulating regulatory T cells.
Using this combination of therapies, it is thought that a clinically significant anti-cancer immune response might be elicited.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| VDC2008 | Experimental | Biological: VDC2008, Drug: CyclophosphamideCryoablation of prostate followed by dendritic cell injection (dose of 2.5 x 10^7, 7.5 x 10^7, or 1.0 x 10^8 cells depending on assigned cohort) into prostate and low dose cyclophosphamide therapy (dose: 25 mg, p.o., b.i.d. for 7 days on and 7 days off; a total of 6 cycles [1 cycle = 4 weeks] starting Week 2 after cryoablation and going to Week 26) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (34 listed)
- Men ≥ 18 years of age and any race.
- Signed Informed Consent document obtained prior to the initiation of screening procedures.
- Histologically documented primary adenocarcinoma of the prostate. A specimen of the primary tumor must be submitted to the Central Pathology Laboratory for confirmation of prostatic adenocarcinoma and determination of Gleason Sum grading.
- Prior history of:
- In case of recurrence, subject must have evidence of prostate cancer by a positive biopsy revealing adenocarcinoma within the past 6 months of screening and confirmed by the Central Pathology Laboratory.
Key exclusion criteria (30 listed)
- The presence of lung, liver or brain metastases, malignant pleural effusions or malignant ascites.
- Moderate or severe symptomatic metastatic disease. Subjects who meet either of the following criteria must be excluded:
- Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2 accessed at study screening visit.
- Chemotherapy treatment at any time prior to study screening.
- Radiation therapy for metastatic disease, including intravenous radioactive strontium therapy.
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 |
|---|---|---|
| VDC2008Also: Autologous dendritic cellsIntratumoral injection of VDC2008 post-cryotherapy. Dosage will depend on cohort: 2.5 x 10^7, 7.5 x 10^7 or 1.0 x 10^8 cells | Biological | VDC2008 |
| CyclophosphamideCyclophosphamide i.v. given at day -3 (dose: 300mg/m2); Low-dose Cyclophosphamide pill given twice daily (dose: 25 mg, p.o., b.i.d. for 7 days on and 7 days off; a total of 6 cycles [1 cycle = 4 weeks] starting Week 2 after cryoablation and going to Week 26) | Drug | VDC2008 |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: Up to 1 year
PROTOCOL EXCERPT: The primary objective of the Phase I Portion of this study is the determination of the maximum tolerated dose (MTD) of intratumorally injected study agent VDC2008 administered following cryoablation of the prostate, and pre- and post-treatment with a low-dose cyclophosphamide therapy, as determined by toxicity and adverse event monitoring following treatment of metastatic androgen-independent prostate cancer. ADDITIONAL INFORMATION: MTD was not reached by any study participant prior to end of the study. Additional participants would have been necessary to determine MTD.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Prostate Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
Active, not recruitingObservational study
MRI Fusion Biopsy vs. Micro-Ultrasound Guided Biopsy
Prostate Cancer
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
Recruiting
Rehabilitation and Sex Therapy to Optimize Recovery After Prostate Cancer Treatment
Prostate Cancer, Urinary Incontinence
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.
Duke K Bahn, M.D. principal investigator
Prostate Institue of America
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing VDC2008 and Cyclophosphamide in people with Prostate Cancer, run by Bostwick Laboratories 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 34 inclusion and 30 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 4 Nov 2014. 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 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?
Yes. Results are posted in the registry (first posted 4 Nov 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Maximum Tolerated Dose (MTD) (time frame: Up to 1 year). 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 4 Nov 2014.