Metastatic Castration Resistant Prostate CancerPhase 1/2ACTIonNCT04458311
Abiraterone Acetate in Combination With Tildrakizumab
A Phase 1/2 study testing Abiraterone Acetate and Tildrakizumab in people with Metastatic Castration Resistant Prostate Cancer, run by Institute of Cancer Research, United Kingdom at 6 sites in 2 countries.
Trial summary
The purpose of this study is to find out the side effects and safety of a combination of the anti-IL23 targeting monoclonal antibody tildrakizumab in combination with abiraterone acetate in men with metastatic castration resistant prostate cancer and to determine the most appropriate dose of this combination. Read more about this study
- Who is it for?
- Ages 18 years and older, men onlyHealthy volunteers can take part
- Conditions the study is for
- Metastatic Castration Resistant Prostate Cancer
- What is being tested?
- Abiraterone Acetate and Tildrakizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 6 sitesin 2 countries
- Study dates
- 1 Dec 2020to 15 Nov 2023
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up.
- Age 18 or above.
- Histologically or cytologically proven adenocarcinoma of the prostate.
- Metastatic castration resistant prostate cancer
- Documented prostate cancer progression as assessed by the investigator with RECIST (v1.1) and PCWG3 criteria with at least one of the following criteria:
- Progression of soft tissue/visceral disease by RECIST (v1.1) and/or,
Show all 17Show fewer
- Progression of bone disease by PCWG3 bone scan criteria and/or,
- Progression of PSA by PCWG3 PSA criteria and/or,
- Clinical progression with worsening pain and need for palliative radiotherapy for bone metastases.
- Patients that have progressed after either enzalutamide or abiraterone treatment (having received a minimum of 12-weeks of enzalutamide or abiraterone).
- Ongoing androgen deprivation with a luteinizing hormone releasing hormone analogue (unless the patient is surgically castrated) maintaining serum testosterone of less than 50 ng/dL (less than 2.0 nM) is mandatory.
- Life expectancy of at least 12-weeks.
- World Health Organisation (WHO) performance status of 0-2
- Able to swallow the study drug.
- Archival tissue must be available for research analysis.
- Patients must have disease that is amenable to biopsy and must be willing to undergo tumour biopsies.
- Haematological and biochemical indices within the required ranges in protocol. These measurements must be performed within two weeks prior to the patient's first dose of any investigational medicinal products (IMP).
Who cannot join
- Patients with predominantly small cell or neuroendocrine differentiated prostate cancer are not eligible.
- Prior therapy, including major surgery, chemotherapy, radium-223, or other anti-cancer therapy within 4-weeks prior to IMP administration. Patients who were receiving abiraterone acetate (Zytiga® or Yonsa™) immediately prior to trial entry will not need to undergo a washout period. The use of bisphosphonates or RANK ligand inhibitors, provided the patient has been on a stable dose without any dose adjustment for at least 30 days prior to combination Cycle 1 Day 1, in patients with known osteopenia or osteoporosis or bone metastases is permitted. A single fraction of palliative radiation is permitted if at least 14-days before starting trial treatment.
- Prior hormonal treatment exclusions as follows:
- prior flutamide treatment during previous four-weeks N.B. Patients whose PSA did not decline in response to antiandrogens given as a second line or later intervention will only require a 14-day washout;
- prior bicalutamide (Casodex) and nilutimide (Nilandron) treatment during previous six-weeks;
- prior progesterone, medroxyprogesterone, progestins, cyproterone acetate, tamoxifen, and 5-alpha reductase inhibitors during previous two-weeks (14-days).
Show all 37Show fewer
- Live vaccine within 4 weeks of starting trial treatment and up to 17 weeks from the last dose of Tildrakizumab.
- Prior limited field radiotherapy within the previous two weeks (14-days), or wide field radiotherapy within the previous four weeks of trial entry.
- Participation in another interventional clinical trial and any concurrent treatment with any investigational drug within four weeks prior to IMP administration.
- Any toxicities due to prior chemotherapy and/or radiotherapy that have not resolved to NCI-CTCAE v5.0 Grade ≤1 with the exception of chemotherapy induced alopecia and Grade 2 peripheral neuropathy.
- Clinical evidence of hyperaldosteronism or hypopituitarism.
- Use of drugs that are known strong CYP3A4 inducers and CYP2D6 substrates with a narrow therapeutic index (please refer to http://medicine.iupui.edu/clinpharm/ddis/table.aspx). Seville orange or grapefruit products, and any herbal medications should be avoided for four weeks prior to starting trial treatment.
- Malabsorption syndrome or other condition that would interfere with enteral absorption of the study drugs.
- Known intracerebral metastases
- Any of the following cardiac criteria:
- QT interval > 470 msec.
- Clinically important abnormalities including rhythm, conduction or ECG changes (left bundle branch block, third degree heart block).
- Factors predisposing to QT prolongation including congenital long QT syndrome; family history of prolonged QT syndrome, unexplained sudden death (under 40); concomitant medications known to prolong QT interval.
- Coronary artery bypass, angioplasty, vascular stent, myocardial infarction, angina or congestive heart failure (NYHA ≥ grade 2) in the last 6 months (see the NYHA scale).
- Uncontrolled hypotension (systolic blood pressure < 90mmHg and or diastolic blood pressure < 50 mmHg).
- Uncontrolled hypertension on optimal medication (systolic blood pressure >180, diastolic blood pressure > 100).
- Patients with known history of adrenal insufficiency or mineralocorticoid excess.
- Patients with a significant history of liver disease (Child-Pugh B or C, viral or other hepatitis, current alcohol abuse or cirrhosis).
- Known history of hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
- At high medical risk because of non-malignant systemic disease including active infection, latent or active TB.
- Known history of tuberculosis.
- Poorly controlled diabetes with HbA1C > 7.5%.
- Malignancy other than prostate cancer within three-years of trial entry with the exception of adequately treated basal cell carcinoma. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy must have no evidence of that disease for at least-three years and be deemed at negligible risk for recurrence, are deemed eligible.
- Immunocompromised patients including patients who have previously received organ transplants or are on long-term immunosuppression (e.g. corticosteroids of > 10 mg daily equivalent of prednisolone).
- Active or uncontrolled autoimmune disease requiring corticosteroid therapy or other forms of systemic immunosuppression.
- Any other finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect interpretation of the results or renders the patients at high risk from treatment complications e.g. patients with a hypersensitivity to tildrakizumab, abiraterone, prednisolone, or any of the drug excipients.
- Patients with female partners of child-bearing potential (unless they agree to take measures not to father children by using a barrier method of contraception [condom plus spermicide] or to sexual abstinence effective from the first administration of any of the study drugs throughout the trial and for six months afterwards. Men with partners of child-bearing potential must also be willing to ensure that their partner uses an effective method of contraception for the same duration for example, hormonal contraception, intrauterine device, diaphragm with spermicidal gel or sexual abstinence). Men with pregnant or lactating partners must be advised to use barrier method contraception (for example, condom plus spermicidal gel) to prevent exposure of the foetus or neonate.
- NB. Abstinence is only considered to be an acceptable method of contraception when this is in line with the preferred and usual lifestyle of the participants. Periodic abstinence (e.g., calendar, ovulation, sympathothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
- Prior bone marrow transplant.
- Extensive radiotherapy to greater than 25% of bone marrow within 8 weeks.
- Any other condition, which in the Investigator's opinion would not make the patient a good candidate for the clinical trial.
- Symptoms of COVID-19 and/or documented COVID-19 infection
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
United Kingdom5 sites
Belfast City Hospital
Belfast, UK
Addenbrooke's Hospital
Cambridge
Cancer Research Centre at Weston Park Hospital
Sheffield, England, S1O 2SJ
University Hospitals Southampton NHS Foundation Trust
Southampton
The Royal Marsden Hospital Foundation Trust
Sutton, UK
About this study
Official title: ACTION: Phase I/II Trial of Abiraterone Acetate in Combination With Tildrakizumab (Anti-IL23 Targeting Monoclonal Antibody) in Men With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
The purpose of this study is to find out the side effects and safety of a combination of the anti-IL23 targeting monoclonal antibody tildrakizumab in combination with abiraterone acetate in men with metastatic castration resistant prostate cancer and to determine the most appropriate dose of this combination. In the Phase I part of this study small groups of patients will be treated with increasing doses of tildrakizumab in combination with a fixed dose of abiraterone acetate (500mg once daily). Once Phase I has been completed the combination with the optimum safety and pharmacokinetic/pharmacodynamic profile will be taken forward to the Phase II part of the study. The Phase II part of the study will evaluate the optimized dose/schedule identified in Phase I of the study in patients with metastatic castration resistant prostate cancer.
Read the detailed description
The trial will be divided into 2 parts: Phase I and Phase II.
The Phase I study will adopt a Bayesian Continual Reassessment Method. Patients will receive single-agent abiraterone run-in of 500 mg orally, once daily (continuous dosing) along with prednisolone at 5 mg BD until PSA progression on abiraterone monotherapy is confirmed. This run-in will not be required if patients have been treated with abiraterone in the previous 6 months. Upon confirmation of PSA progression, tildrakizumab IV will be started and given once every 4-weeks in combination with the fixed dose abiraterone (and prednisolone). The starting dose of tildrakizumab will be 100mg, with single dose escalations to 300mg and 600mg to determine the RP2D to take forward to the Phase II study. Depending on the number of responses observed, dose levels that are deemed tolerable may be expanded to up to a total of 10 patients who are evaluable for response.
The Phase II study will employ a two-stage Minimax design, recruiting up to 25 patients. During the first stage, 15 evaluable patients will be enrolled and followed for a minimum of 2 cycles each. If there are one or more responses confirmed at least 4-weeks later, an additional 10 evaluable patients will be recruited. If 4 or more responses are seen in the 25 patients evaluable for response, the combination will be deemed successful, warranting further evaluation in subsequent phases of testing. In the phase II study, patients will start taking 500mg abiraterone as an oral tablet once daily along with 5mg of prednisolone twice daily until PSA progression on abiraterone monotherapy is confirmed. This run-in will not be required if patients have been treated with abiraterone in the previous 6 months. Upon confirmation of PSA progression, the tildrakizumab will be given as an intravenous infusion at the dose established in the Phase I safety part of the study in combination with the abiraterone (and prednisolone) from combination Cycle 1 Day 1 onwards.
- Being tested
- Abiraterone Acetate, Tildrakizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Abiraterone AcetateDrug
Also called Yonsa
Supplied as 125 mg tablets
TildrakizumabDrug
Tildrakizumab will be supplied in single-use 100 mg/mL glass vials intended for IV infusion.
| Study group | Role | What they receive |
|---|---|---|
| Phase I | Experimental | Increasing doses of tildrakizumab in combination with a fixed dose of abiraterone to establish the recommended phase II dose in patients with metastatic castration resistant prostate cancer.. Receives: Drug: Abiraterone Acetate; Drug: Tildrakizumab |
| Phase II | Experimental | The Phase II part of the study will evaluate the recommended phase II dose identified in Phase I of the study in patients with metastatic castration resistant prostate cancer. Receives: Drug: Abiraterone Acetate; Drug: Tildrakizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I - To describe the safety and tolerability of abiraterone acetate and tildrakizumab when given in combination. To establish a RP2D for tildrakizumab, in combination with abiraterone.
To determine a maximum tolerated dose (MTD) of tildrakizumab by establishing the dose at which the DLT rate is as close to the target DLT rate of 15% as possible, in combination with abiraterone at 500 mg OD with prednisolone at 5 mg bid, and is deemed to be tolerable by the Safety Review Committee. This will be the RP2D for tildrakizumab.
Measured: 20 months
Phase II - To determine the antitumour activity of tildrakizumab (at RP2D) in combination with abiraterone in men with mCRPC.
Antitumour activity will be defined by response rate on the basis of the following outcomes. If any of the following occur, patients will be considered to have responded:
- PSA decline ≥ 50% criteria confirmed 4-weeks or later and/or,
- Confirmed soft tissue objective response by RECIST (v1.1) in patients with measurable disease and/or,
- ONLY for patients with detectable circulating tumour cell (CTC) count of ≥ 5/7.5ml blood at baseline, conversion of CTC count to <5/7.5ml blood nadir.
Measured: 12 months
Secondary outcomes (19)
Phase I - To investigate the PD effects of the tildrakizumab and abiraterone combination in men with mCRPC.
Measuring the impact of the downregulation of IL-23 signaling in tumour, also evaluating the downregulation of androgen receptor (AR), AR splice variants, and AR target genes.
Measured: 20 months
Phase I - To characterize the PK profile of the tildrakizumab and abiraterone combination in men with mCRPC - CMax.
Determine peak plasma concentration (Cmax) of tildrakizumab and abiraterone when dosed together.
Measured: 20 months
Phase I - To characterize the PK profile of the tildrakizumab and abiraterone combination in men with mCRPC - T1⁄2.
Determine the terminal elimination half-life (T1⁄2) of tildrakizumab and abiraterone when dosed together.
Measured: 20 months
Phase I - To characterize the PK profile of the tildrakizumab and abiraterone combination in men with mCRPC - AUC
Determine the area under the plasma concentration versus time curve (AUC) of tildrakizumab and abiraterone when dosed together.
Measured: 20 months
Phase I - To identify molecular determinants of response and anti-tumour activity of the combination of tildrakizumab and abiraterone in men with mCRPC.
Determine biomarkers of response, including but not limited to PTEN loss, MYC amplification, and intra-tumour MDSC counts, in tumour biopsies from responders and non-responders.
Measured: 20 months
Phase I - To determine preliminary anti-tumour activity of the tildrakizumab and abiraterone combination in men with mCRPC.
Response and progression will be determined using the same measures as that described for the primary objective of the Phase II study.
Measured: 20 months
Phase I - To evaluate progression-free survival (PFS) in mCRPC patients receiving the tildrakizumab and abiraterone combination.
PFS will be measured from the date of addition of tildrakizumab to abiraterone to the date of progression as determined by radiological criteria (RECIST v 1.1, PCWG3 bone scan criteria) or unequivocal clinical progression necessitating drug discontinuation (e.g. worsening pain, spinal cord compression, need for other anticancer therapy).
Measured: 20 months
Phase I - To estimate the OS in mCRPC patients receiving the combination of tildrakizumab and abiraterone.
OS will be measured from the date of addition of tildrakizumab to abiraterone to the date of death (whatever cause).
Measured: 20 months
Phase II - To evaluate PFS in mCRPC patients receiving the tildrakizumab and abiraterone combination.
PFS will be measured from the date of addition of tildrakizumab to abiraterone to the date of progression as determined by radiological criteria (RECIST v 1.1, PCWG3 bone scan criteria) or unequivocal clinical progression necessitating drug discontinuation (e.g. worsening pain, spinal cord compression, need for other anticancer therapy).
Measured: 12 months
Phase II - To estimate the biochemical anti-tumour activity of tildrakizumab and abiraterone in mCRPC patients - time to PSA progression.
The time to PSA Progression will be measured from the date of addition of tildrakizumab to abiraterone.
Measured: 12 months
Phase II - To estimate the biochemical anti-tumour activity of tildrakizumab and abiraterone in mCRPC patients - duration of PSA decline by ≥ 50%.
The duration of PSA decline by ≥ 50%, where this is seen in responding patients.
Measured: 12 months
Phase II - To estimate the biochemical anti-tumour activity of tildrakizumab and abiraterone in mCRPC patients - maximum PSA decline.
The maximum PSA decline experienced per patient. This will be measured following the addition of tildrakizumab to abiraterone.
Measured: 12 months
Phase II - To estimate the biochemical anti-tumour activity of tildrakizumab and abiraterone in mCRPC patients - maximum percentage of PSA decline.
The maximum percentage of PSA decline experienced per patient. This will be measured following the addition of tildrakizumab to abiraterone.
Measured: 12 months
Phase II - To determine the pattern of radiologic response to tildrakizumab and abiraterone in mCRPC patients.
Time to radiological progression (RECIST 1.1 \& PCWG3 Bone Scan criteria). Radiologic PFS (rPFS).
Measured: 12 months
Phase II - To identify molecular determinants of response and anti-tumour activity of the combination of tildrakizumab and abiraterone in men with mCRPC.
Determine biomarkers of response, including but not limited to PTEN loss, MYC amplification, and intra-tumour MDSC counts, in tumour biopsies from responders and non-responders.
Measured: 12 months
Phase II - To further investigate the PD effects of the tildrakizumab and abiraterone combination in men with mCRPC.
Measure the impact of the downregulation of IL-23 signaling in tumour, also evaluating the downregulation of androgen receptor (AR), AR splice variants, and AR target genes
Measured: 12 months
Phase II - To determine the rate of response based on CTC conversion.
Rate of CTC conversion from ≥ 5/7.5 ml blood to < 5/7.5 ml
Measured: 12 months
Phase II - To estimate the OS in mCRPC patients receiving the combination of tildrakizumab and abiraterone.
OS will be measured from the date of addition of tildrakizumab to abiraterone to the date of death (whatever cause).
Measured: 12 months
Phase II - To further characterise the safety and tolerability profile of the combination of tildrakizumab and abiraterone in men with mCRPC.
Causality and grading severity of each adverse event related to the tildrakizumab and abiraterone combination according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2020
- Study start1 Dec 2020
- Primary completion1 Apr 2023
- Study completion15 Nov 2023
Why it stopped: Funder decided that response outcomes to date did not support continuation of the study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Castration Resistant Prostate CancerStudies of the same condition, open and under way.
- More trials run by Institute of Cancer Research, United KingdomThe 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
- Health services research
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institute of Cancer Research, United Kingdom
- Sponsor type
- University, hospital or other
- Collaborators
- Sun Pharmaceutical Industries Limited
- Responsible party
- Sponsor
- Investigators
- Johann De Bono, MD, Study director, National Health Service, United Kingdom
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04458311
- Sponsor's protocol ID
- CCR5163
- Acronym
- ACTIon
- Status last verified
- Apr 2024
- First submitted
- 11 Jun 2020
- Last updated
- 25 Apr 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ACTION: Phase I/II Trial of Abiraterone Acetate in Combination With Tildrakizumab (Anti-IL23 Targeting Monoclonal Antibody) in Men With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
- ClinicalTrials.gov ID
- NCT04458311
- Acronym / sponsor ID
- ACTIon / CCR5163
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funder decided that response outcomes to date did not support continuation of the study.
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Institute of Cancer Research, United KingdomUniversity, hospital or other
- Collaborators
- Sun Pharmaceutical Industries Limited
- Study start
- 1 Dec 2020 (actual)
- Primary completion
- 1 Apr 2023 (actual)
- Study completion
- 15 Nov 2023 (actual)
- First posted
- 7 Jul 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.
The purpose of this study is to find out the side effects and safety of a combination of the anti-IL23 targeting monoclonal antibody tildrakizumab in combination with abiraterone acetate in men with metastatic castration resistant prostate cancer and to determine the most appropriate dose of this combination. In the Phase I part of this study small groups of patients will be treated with increasing doses of tildrakizumab in combination with a fixed dose of abiraterone acetate (500mg once daily). Once Phase I has been completed the combination with the optimum safety and pharmacokinetic/pharmacodynamic profile will be taken forward to the Phase II part of the study. The Phase II part of the study will evaluate the optimized dose/schedule identified in Phase I of the study in patients with metastatic castration resistant prostate cancer.
Detailed description
The trial will be divided into 2 parts: Phase I and Phase II.
The Phase I study will adopt a Bayesian Continual Reassessment Method. Patients will receive single-agent abiraterone run-in of 500 mg orally, once daily (continuous dosing) along with prednisolone at 5 mg BD until PSA progression on abiraterone monotherapy is confirmed. This run-in will not be required if patients have been treated with abiraterone in the previous 6 months. Upon confirmation of PSA progression, tildrakizumab IV will be started and given once every 4-weeks in combination with the fixed dose abiraterone (and prednisolone). The starting dose of tildrakizumab will be 100mg, with single dose escalations to 300mg and 600mg to determine the RP2D to take forward to the Phase II study. Depending on the number of responses observed, dose levels that are deemed tolerable may be expanded to up to a total of 10 patients who are evaluable for response.
The Phase II study will employ a two-stage Minimax design, recruiting up to 25 patients. During the first stage, 15 evaluable patients will be enrolled and followed for a minimum of 2 cycles each. If there are one or more responses confirmed at least 4-weeks later, an additional 10 evaluable patients will be recruited. If 4 or more responses are seen in the 25 patients evaluable for response, the combination will be deemed successful, warranting further evaluation in subsequent phases of testing. In the phase II study, patients will start taking 500mg abiraterone as an oral tablet once daily along with 5mg of prednisolone twice daily until PSA progression on abiraterone monotherapy is confirmed. This run-in will not be required if patients have been treated with abiraterone in the previous 6 months. Upon confirmation of PSA progression, the tildrakizumab will be given as an intravenous infusion at the dose established in the Phase I safety part of the study in combination with the abiraterone (and prednisolone) from combination Cycle 1 Day 1 onwards.
Study design
- Primary purpose
- Health services research
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase I | Experimental | Drug: Abiraterone Acetate, Drug: TildrakizumabIncreasing doses of tildrakizumab in combination with a fixed dose of abiraterone to establish the recommended phase II dose in patients with metastatic castration resistant prostate cancer.. |
| Phase II | Experimental | Drug: Abiraterone Acetate, Drug: TildrakizumabThe Phase II part of the study will evaluate the recommended phase II dose identified in Phase I of the study in patients with metastatic castration resistant prostate cancer. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up.
- Age 18 or above.
- Histologically or cytologically proven adenocarcinoma of the prostate.
- Metastatic castration resistant prostate cancer
- Documented prostate cancer progression as assessed by the investigator with RECIST (v1.1) and PCWG3 criteria with at least one of the following criteria:
Key exclusion criteria (37 listed)
- Patients with predominantly small cell or neuroendocrine differentiated prostate cancer are not eligible.
- Prior therapy, including major surgery, chemotherapy, radium-223, or other anti-cancer therapy within 4-weeks prior to IMP administration. Patients who were receiving abiraterone acetate (Zytiga® or Yonsa™) immediately prior to trial entry will not need to undergo a washout period. The use of bisphosphonates or RANK ligand inhibitors, provided the patient has been on a stable dose without any dose adjustment for at least 30 days prior to combination Cycle 1 Day 1, in patients with known osteopenia or osteoporosis or bone metastases is permitted. A single fraction of palliative radiation is permitted if at least 14-days before starting trial treatment.
- Prior hormonal treatment exclusions as follows:
- Live vaccine within 4 weeks of starting trial treatment and up to 17 weeks from the last dose of Tildrakizumab.
- Prior limited field radiotherapy within the previous two weeks (14-days), or wide field radiotherapy within the previous four weeks of trial entry.
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 |
|---|---|---|
| Abiraterone AcetateAlso: YonsaSupplied as 125 mg tablets | Drug | Phase I, Phase II |
| TildrakizumabTildrakizumab will be supplied in single-use 100 mg/mL glass vials intended for IV infusion. | Drug | Phase I, Phase II |
Primary outcome
Phase I - To describe the safety and tolerability of abiraterone acetate and tildrakizumab when given in combination. To establish a RP2D for tildrakizumab, in combination with abiraterone.
Time frame: 20 months
To determine a maximum tolerated dose (MTD) of tildrakizumab by establishing the dose at which the DLT rate is as close to the target DLT rate of 15% as possible, in combination with abiraterone at 500 mg OD with prednisolone at 5 mg bid, and is deemed to be tolerable by the Safety Review Committee. This will be the RP2D for tildrakizumab.
Phase II - To determine the antitumour activity of tildrakizumab (at RP2D) in combination with abiraterone in men with mCRPC.
Time frame: 12 months
Antitumour activity will be defined by response rate on the basis of the following outcomes. If any of the following occur, patients will be considered to have responded: * PSA decline ≥ 50% criteria confirmed 4-weeks or later and/or, * Confirmed soft tissue objective response by RECIST (v1.1) in patients with measurable disease and/or, * ONLY for patients with detectable circulating tumour cell (CTC) count of ≥ 5/7.5ml blood at baseline, conversion of CTC count to <5/7.5ml blood nadir.
19 secondary outcomes
Phase I - To investigate the PD effects of the tildrakizumab and abiraterone combination in men with mCRPC.
Time frame: 20 months
Phase I - To characterize the PK profile of the tildrakizumab and abiraterone combination in men with mCRPC - CMax.
Time frame: 20 months
Phase I - To characterize the PK profile of the tildrakizumab and abiraterone combination in men with mCRPC - T1⁄2.
Time frame: 20 months
Phase I - To characterize the PK profile of the tildrakizumab and abiraterone combination in men with mCRPC - AUC
Time frame: 20 months
Phase I - To identify molecular determinants of response and anti-tumour activity of the combination of tildrakizumab and abiraterone in men with mCRPC.
Time frame: 20 months
Phase I - To determine preliminary anti-tumour activity of the tildrakizumab and abiraterone combination in men with mCRPC.
Time frame: 20 months
Phase I - To evaluate progression-free survival (PFS) in mCRPC patients receiving the tildrakizumab and abiraterone combination.
Time frame: 20 months
Phase I - To estimate the OS in mCRPC patients receiving the combination of tildrakizumab and abiraterone.
Time frame: 20 months
Phase II - To evaluate PFS in mCRPC patients receiving the tildrakizumab and abiraterone combination.
Time frame: 12 months
Phase II - To estimate the biochemical anti-tumour activity of tildrakizumab and abiraterone in mCRPC patients - time to PSA progression.
Time frame: 12 months
Phase II - To estimate the biochemical anti-tumour activity of tildrakizumab and abiraterone in mCRPC patients - duration of PSA decline by ≥ 50%.
Time frame: 12 months
Phase II - To estimate the biochemical anti-tumour activity of tildrakizumab and abiraterone in mCRPC patients - maximum PSA decline.
Time frame: 12 months
Phase II - To estimate the biochemical anti-tumour activity of tildrakizumab and abiraterone in mCRPC patients - maximum percentage of PSA decline.
Time frame: 12 months
Phase II - To determine the pattern of radiologic response to tildrakizumab and abiraterone in mCRPC patients.
Time frame: 12 months
Phase II - To identify molecular determinants of response and anti-tumour activity of the combination of tildrakizumab and abiraterone in men with mCRPC.
Time frame: 12 months
Phase II - To further investigate the PD effects of the tildrakizumab and abiraterone combination in men with mCRPC.
Time frame: 12 months
Phase II - To determine the rate of response based on CTC conversion.
Time frame: 12 months
Phase II - To estimate the OS in mCRPC patients receiving the combination of tildrakizumab and abiraterone.
Time frame: 12 months
Phase II - To further characterise the safety and tolerability profile of the combination of tildrakizumab and abiraterone in men with mCRPC.
Time frame: 12 months
Results and safety
The study was stopped early (reason given: Funder decided that response outcomes to date did not support continuation of the study.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2024.
Related trials for Metastatic Castration Resistant Prostate Cancer
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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
RecruitingPhase 2
A Study to Test Inavolisib Treatment in Participants With Metastatic Castration-Resistant Prostate Cancer
Metastatic Castration-Resistant Prostate Cancer
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
RecruitingObservational study
ARCTIC: Liquid Biomarkers in the Prospective Androgen Receptor Signaling Inhibitors (ARSI) Resistance Clinical Trials
Prostate Cancer, Prostate Adenocarcinoma
Active, not recruitingPhase 2
FPI-2265 (225Ac-PSMA-I&T) and Olaparib for Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Metastatic Castration-resistant Prostate 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.
Johann De Bono, MD study director
National Health Service, United Kingdom
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Abiraterone Acetate and Tildrakizumab in people with Metastatic Castration Resistant Prostate Cancer, run by Institute of Cancer Research, United Kingdom at 6 sites in 2 countries.
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 37 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 25 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 6 sites in United Kingdom, Switzerland. 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?
The study was stopped early (reason given: Funder decided that response outcomes to date did not support continuation of the study.). 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?
Phase I - To describe the safety and tolerability of abiraterone acetate and tildrakizumab when given in combination. To establish a RP2D for tildrakizumab, in combination with abiraterone. (time frame: 20 months). The study lists 2 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 25 Apr 2024.