Abiraterone Acetate in Combination With Tildrakizumab

NCT04458311 | Terminated Phase 1 FDA Drug

• 1 other identifier: CCR5163
• Study Type: interventional
• Target: 13
• Locations: 2 countries
• Sites: 6

Brief 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. 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.

Conditions

Metastatic Castration Resistant Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  12 months

Secondary Outcomes (19)

• Phase I - To investigate the PD effects of the tildrakizumab and abiraterone combination in men with mCRPC.

  20 months

• Phase I - To characterize the PK profile of the tildrakizumab and abiraterone combination in men with mCRPC - CMax.

  20 months

• Phase I - To characterize the PK profile of the tildrakizumab and abiraterone combination in men with mCRPC - T1⁄2.

  20 months

• Phase I - To characterize the PK profile of the tildrakizumab and abiraterone combination in men with mCRPC - AUC

  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.

  20 months

Other Outcomes (2)

• To determine mechanisms of resistance to the combination of tildrakizumab and abiraterone.

  32 months

• To assess putative predictive biomarkers of response to this combination.

  32 months

Study Arms (2)

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..

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.

Drug: Abiraterone Acetate; Drug: Tildrakizumab

Interventions

Abiraterone Acetate DRUG

Supplied as 125 mg tablets

Also known as: Yonsa

Phase I; Phase II

Tildrakizumab DRUG

Tildrakizumab will be supplied in single-use 100 mg/mL glass vials intended for IV infusion.

Phase I; Phase II

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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,
• 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.

You may not qualify if:

• 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 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).
• 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.

Sponsors & Collaborators

• Institute of Cancer Research, United Kingdom: lead
• Sun Pharmaceutical Industries Limited: collaborator

Study Sites (6)

Bellinzona Hospital

Bellinzona, Switzerland

Location

Cancer Research Centre at Weston Park Hospital

Sheffield, England, S1O 2SJ, United Kingdom

Location

Belfast City Hospital

Belfast, UK, United Kingdom

Location

The Royal Marsden Hospital Foundation Trust

Sutton, UK, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, United Kingdom

Location

University Hospitals Southampton NHS Foundation Trust

Southampton, United Kingdom

Location

MeSH Terms

Interventions

Abiraterone Acetate; tildrakizumab

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Johann De Bono, MD

  National Health Service, United Kingdom

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2020
• First Posted: July 7, 2020
• Study Start: December 1, 2020
• Primary Completion: April 1, 2023
• Study Completion: November 15, 2023
• Last Updated: April 25, 2024

Record last verified: 2024-04

Locations

CH (1); GB (5)