Prostate CancerPhase 1NCT04633148
Dose-escalating Trial With UniCAR02-T Cells and PSMA Target Module (TMpPSMA) in Patients With Progressive Disease After Standard Systemic Therapy in Cancers With Positive PSMA Marker
A Phase 1 study testing Cyclophosphamide (Non-IMP), Fludarabine (Non-IMP) and UniCAR02-T-pPSMA in people with Prostate Cancer, run by AvenCell Europe GmbH at 4 sites in Germany.
Trial summary
This dose-escalating phase I trial assesses for the first time the safety, the side effects and the harmlessness, as well as the therapeutical benefit of the new study drug UniCAR02-T-pPSMA in patients with progressive disease after standard systemic therapy in castration-resistant prostate cancers with positive PSMA… 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?
- Cyclophosphamide (Non-IMP), Fludarabine (Non-IMP) and UniCAR02-T-pPSMA
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 4 sitesGermany
- Study dates
- 23 Nov 2020to 28 Mar 2024
- 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
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- Patients diagnosed with progressive castration-resistant prostate cancer refractory to standard treatments and with no other available standard or curative treatment
- Measurable or non-measurable disease based on immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) and positivity in PSMA Positron Emission Tomography (PET)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- Life expectancy of at least 3 months
- Adequate renal and hepatic laboratory assessments
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- Adequate cardiac function, i.e. left ventricular ejection fraction (LVEF)
- Permanent venous access existing (e.g. port-system) resp. acceptance of implantation of a device
- Able to give written informed consent
- Weight ≥ 45kg
- Using a highly effective method of birth control
Who cannot join
- Central nervous system metastasis or meningeosis carcinomatosa
- Cardiac disease: i.e. heart failure (NYHA III or IV); unstable coronary artery disease, myocardial infarction or serious cardiac ventricular arrhythmias requiring anti-arrhythmic therapy within the last 6 months prior to study entry
- Patients undergoing renal dialysis
- Pulmonary disease with clinical relevant hypoxia (need for oxygen inhalation)
- Parkinson, epilepsy and stroke or presence or history of seizures, paresis, aphasia, central nervous system (CNS) or intracranial hemorrhage
- History or presence of disseminated intravascular coagulation (DIC) or thromboembolism within the last three months
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- Multiple sclerosis
- Hemolytic anemia
- Eye diseases with neovascularization
- Active infectious disease considered by investigator to be incompatible with protocol or being contraindications for lymphodepletion therapy
- Presence of urotoxicity from previous chemo- or radiotherapy or urinary outflow obstruction
- Vaccination with live viruses less than 2 weeks prior lymphodepletion therapy
- Any disease requiring immunosuppressive therapy
- Major surgery within 28 days (prior start of TMpPSMA infusion)
- Other malignancy requiring active therapy but adjuvant endocrine therapy is allowed
- Treatment with any investigational drug substance or experimental therapy within 4 weeks or 5 half-lives of the substance (whatever is shorter) prior to administration of TMpPSMA
- Prior treatment with gene therapy products
- Use of checkpoint inhibitors within 5 half-lives of the respective substance prior to administration of TMpPSMA
- Autoimmune diseases requiring systemic steroids or other systemic immunosuppressants (note that physiologic steroid replacement not exceeding 10 mg prednisolone equivalent per day is allowed)
- Psychologic disorders, drug and/or significant active alcohol abuse
- Known history of human immunodeficiency virus (HIV) or active/chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV)
- Presence of autoantibodies against La/SS-B or presence or history of autoimmune diseases (e.g. systemic lupus erythematosus, SS/SLE overlap syndrome, subacute cutaneous lupus erythematosus, neonatal lupus, primary biliary cirrhosis, Sjögren's syndrome)
- Known hypersensitivity to cellular component (UniCAR02-T) and/or targeting peptide module (TMpPSMA) excipients and/or contraindication to compounds of the lymphodepletion therapy (cyclophosphamide and fludarabine), and tocilizumab or corticosteroids as specified in the respective IB/SmPC
- Evidence suggesting that the patient is not likely to follow the study protocol (e.g. lacking compliance)
- Incapability of understanding purpose and possible consequences of the trial
- Patients who should not be included according to the opinion of the investigator
Trial locations and contacts
4 sites in 1 country.
Germany4 sites
Universitätsklinikum Dresden
Dresden, Saxony, 01307
Universitätsklinikum Hamburg-Eppendorf
Hamburg, 20246
Universitätsklinikum Ulm
Ulm, Baden-Wurttemberg, 89081
Universitätsklinikum Würzburg
Würzburg, Bavaria, 97080
About this study
Official title: Multicenter, Open-label, Adaptive Design Phase I Trial With Genetically Modified T-cells Carrying Universal Chimeric Antigen Receptors (UniCAR02-T) in Combination With PSMA Peptide Target Module (TMpPSMA) for the Treatment of Patients With Progressive Disease After Standard Systemic Therapy in Cancers With Positive PSMA Marker
This dose-escalating phase I trial assesses for the first time the safety, the side effects and the harmlessness, as well as the therapeutical benefit of the new study drug UniCAR02-T-pPSMA in patients with progressive disease after standard systemic therapy in castration-resistant prostate cancers with positive PSMA marker. The UniCAR02-T-pPSMA drug is a combination of a cellular component (UniCAR02-T) with a recombinant antibody derivative (TMpPSMA) which together forms the active drug.
- Conditions
- Prostate Cancer
- Being tested
- Cyclophosphamide (Non-IMP), Fludarabine (Non-IMP), UniCAR02-T-pPSMA, UniCAR02-T (IMP)
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cyclophosphamide (Non-IMP)Drug
Intravenous infusion for 3 days
Fludarabine (Non-IMP)Drug
Intravenous infusion for 3 days
UniCAR02-T-pPSMADrug
Intravenous Infusion for 21 days
UniCAR02-T (IMP)Drug
Intravenous infusion of single dose
| Study group | Role | What they receive |
|---|---|---|
| UniCAR02-T-pPSMA | Experimental | Preconditioning (lymphodepletion) with cyclophosphamide and fludarabine, followed by combination treatment of genetically modified T-cells carrying universal chimeric antigen receptors (UniCAR02-T) with the peptide TMpPSMA. Receives: Drug: Cyclophosphamide (Non-IMP); Drug: Fludarabine (Non-IMP); Drug: UniCAR02-T-pPSMA; Drug: UniCAR02-T (IMP) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability
Incidence and intensity of adverse events graded according to CTCAE V5.0 with the exception of CRS and ICANS graded according to Lee et al. 2014 and Lee et al. 2019 respectively
Measured: DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)
Incidence of dose limiting toxicity (DLT)
DLT is defined as any adverse event at least possible related to TMpPSMA and/or UniCAR02-T
Measured: DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)
Maximum tolerated dose (MTD)
The dose for which the isotonic estimate of the DLT probability is closest to the target DLT probability of 0.2.
Measured: DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)
Secondary outcomes (5)
Recommended phase 2 dose (RP2D)
The RP2D will be determined based on MTD, all available efficacy data, and all available safety data, including information derived from additional treatment cycles.
Measured: DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)
Antitumor activity
Antitumor activity of UniCAR02-T-pPSMA at any time point according to irRECIST (immune-related) Response Evaluation Criteria in Solid Tumors): Complete remission (CR) and partial remission (PR), Objective response rate (ORR), Disease control rate (DCR), Best response rate, Duration of response (DOR),Progression free survival (PFS)
Measured: DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)
Prostate specific antigen (PSA) response
Measured: DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)
Overall Survival (OS)
Measured: Until fifteen years after last UniCAR02-T administration
Influence on Circulating tumor cells (CTC)
Measured: Before start of lymphodepletion therapy until 6 resp. 12 months after start of last TMpPSMA application
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2020
- Study start23 Nov 2020
- Primary completion28 Mar 2024
- Study completion28 Mar 2024
Why it stopped: Although IMP has been well tolerated, biological activity was very limited. The sponsor concluded that continued development of IMP would be unlikely to result in meaningful clinical benefit for patients with prostate cancer.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- Initial dose escalation followed an adaptive design. Further dose escalation includes 2 additional TMpPSMA dose levels and follows a 3+3 design.
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- AvenCell Europe GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- PHARMALOG Institut für klinische Forschung GmbH
- Responsible party
- Sponsor
- Investigators
- Ralf Bargou, Prof., Principal investigator, Wuerzburg University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04633148
- Sponsor's protocol ID
- UC02-PSMA-01
- Other IDs
- 2019-004211-32, 2019
- Status last verified
- Apr 2024
- First submitted
- 11 Nov 2020
- Last updated
- 23 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter, Open-label, Adaptive Design Phase I Trial With Genetically Modified T-cells Carrying Universal Chimeric Antigen Receptors (UniCAR02-T) in Combination With PSMA Peptide Target Module (TMpPSMA) for the Treatment of Patients With Progressive Disease After Standard Systemic Therapy in Cancers With Positive PSMA Marker
- ClinicalTrials.gov ID
- NCT04633148
- Acronym / sponsor ID
- UC02-PSMA-01
- Conditions
- Prostate Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Although IMP has been well tolerated, biological activity was very limited. The sponsor concluded that continued development of IMP would be unlikely to result in meaningful clinical benefit for patients with prostate cancer.
- Enrolment
- 16 participants (actual)
- Lead sponsor
- AvenCell Europe GmbHIndustry (pharma, biotech, devices)
- Collaborators
- PHARMALOG Institut für klinische Forschung GmbH
- Study start
- 23 Nov 2020 (actual)
- Primary completion
- 28 Mar 2024 (actual)
- Study completion
- 28 Mar 2024 (actual)
- First posted
- 18 Nov 2020 (actual)
- 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 dose-escalating phase I trial assesses for the first time the safety, the side effects and the harmlessness, as well as the therapeutical benefit of the new study drug UniCAR02-T-pPSMA in patients with progressive disease after standard systemic therapy in castration-resistant prostate cancers with positive PSMA marker. The UniCAR02-T-pPSMA drug is a combination of a cellular component (UniCAR02-T) with a recombinant antibody derivative (TMpPSMA) which together forms the active drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Initial dose escalation followed an adaptive design. Further dose escalation includes 2 additional TMpPSMA dose levels and follows a 3+3 design.
| Arm | Type | Receives |
|---|---|---|
| UniCAR02-T-pPSMA | Experimental | Drug: Cyclophosphamide (Non-IMP), Drug: Fludarabine (Non-IMP), Drug: UniCAR02-T-pPSMA, Drug: UniCAR02-T (IMP)Preconditioning (lymphodepletion) with cyclophosphamide and fludarabine, followed by combination treatment of genetically modified T-cells carrying universal chimeric antigen receptors (UniCAR02-T) with the peptide TMpPSMA. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age ≥ 18 years
- Patients diagnosed with progressive castration-resistant prostate cancer refractory to standard treatments and with no other available standard or curative treatment
- Measurable or non-measurable disease based on immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) and positivity in PSMA Positron Emission Tomography (PET)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- Life expectancy of at least 3 months
Key exclusion criteria (26 listed)
- Central nervous system metastasis or meningeosis carcinomatosa
- Cardiac disease: i.e. heart failure (NYHA III or IV); unstable coronary artery disease, myocardial infarction or serious cardiac ventricular arrhythmias requiring anti-arrhythmic therapy within the last 6 months prior to study entry
- Patients undergoing renal dialysis
- Pulmonary disease with clinical relevant hypoxia (need for oxygen inhalation)
- Parkinson, epilepsy and stroke or presence or history of seizures, paresis, aphasia, central nervous system (CNS) or intracranial hemorrhage
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 |
|---|---|---|
| Cyclophosphamide (Non-IMP)Intravenous infusion for 3 days | Drug | UniCAR02-T-pPSMA |
| Fludarabine (Non-IMP)Intravenous infusion for 3 days | Drug | UniCAR02-T-pPSMA |
| UniCAR02-T-pPSMAIntravenous Infusion for 21 days | Drug | UniCAR02-T-pPSMA |
| UniCAR02-T (IMP)Intravenous infusion of single dose | Drug | UniCAR02-T-pPSMA |
Primary outcome
Safety and tolerability
Time frame: DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)
Incidence and intensity of adverse events graded according to CTCAE V5.0 with the exception of CRS and ICANS graded according to Lee et al. 2014 and Lee et al. 2019 respectively
Incidence of dose limiting toxicity (DLT)
Time frame: DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)
DLT is defined as any adverse event at least possible related to TMpPSMA and/or UniCAR02-T
Maximum tolerated dose (MTD)
Time frame: DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)
The dose for which the isotonic estimate of the DLT probability is closest to the target DLT probability of 0.2.
5 secondary outcomes
Recommended phase 2 dose (RP2D)
Time frame: DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)
Antitumor activity
Time frame: DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)
Prostate specific antigen (PSA) response
Time frame: DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)
Overall Survival (OS)
Time frame: Until fifteen years after last UniCAR02-T administration
Influence on Circulating tumor cells (CTC)
Time frame: Before start of lymphodepletion therapy until 6 resp. 12 months after start of last TMpPSMA application
Results and safety
The study was stopped early (reason given: Although IMP has been well tolerated, biological activity was very limited. The sponsor concluded that continued development of IMP would be unlikely to result in meaningful clinical benefit for patients with prostate cancer.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2024.
- Individual participant dataSharing planned: No
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RecruitingObservational study
PULSE Registry: for Patients Receiving Lutetium (177Lu) Vipivotide Tetraxetan
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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.
Ralf Bargou, Prof. principal investigator
Wuerzburg University Hospital
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 Cyclophosphamide (Non-IMP), Fludarabine (Non-IMP) and UniCAR02-T-pPSMA in people with Prostate Cancer, run by AvenCell Europe GmbH at 4 sites in Germany.
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 11 inclusion and 26 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 23 Apr 2024. 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 Germany. 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: Although IMP has been well tolerated, biological activity was very limited. The sponsor concluded that continued development of IMP would be unlikely to result in meaningful clinical benefit for patients with prostate cancer.). 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?
Safety and tolerability (time frame: DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)). The study lists 3 primary outcomes in all. 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 23 Apr 2024.