Study to Evaluate the Safety and Tolerability of RXC004 in Advanced Malignancies
Study Details
Study Description
Brief Summary
The purpose of this study is to determine the safety and tolerability of RXC004 as monotherapy and in combination with Nivolumab in patients with advanced malignancies. In order to define the doses and schedules for further clinical evaluation.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
The study will consist of an ascending monotherapy dose, the doses are pre-defined.
The decision to escalate will be made upon the assessment of safety and tolerability data in the first cycle of treatment.
Module 1 will commence with a 3+3 dose escalation design up to a recommended Phase 2 monotherapy dose. Patients being monitored for dose limiting toxicities at each dose level.
Characterisation of the PK profile, MTD and/or recommended Phase 2 dose will be defined on the emerging data
Module 2: RXC004 and Nivolumab - Follows a similar 3+3 dose escalation design using RXC004 plus Nivolumab. The MTD and/or Phase 2 dose will be defined based on the PK profile, emerging safety and the appearance of any dose limiting toxicities
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: Monotherapy RXC004 - Module 1 Patients will be given RXC004 at a specified dose level and reviewed for Dose Limiting Toxicities Once the DLT period is complete RXC004 will be given at a higher dose until MTD |
Drug: RXC004
RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway
|
| Other: Combination RXC004 plus Nivolumab - Module 2 Patients will be given RXC004 at specific doses in combination with a standard dose of Nivolumab and reviewed for Dose Limiting Toxicities Once the DLT period is complete RXC004 will be given at a higher dose until MTD |
Drug: RXC004
RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway
Drug: Nivolumab
Nivolumab is a fully human monoclonal immunoglobulin G4 antibody to PD-1
|
Outcome Measures
Primary Outcome Measures
- Module 1 - Safety and Tolerability of RXC004 by assessment of whether any Dose Limiting Toxicities (DLT) arise from first dose until the end of 21 days of continuous dosing [The DLT period will be assessed from the first dose until the end of 21 days of continuous dosing. This will be completed for each dose level until a Maximum Tolerated Dose (MTD) is identified. Estimated time 12 Months in total]
A DLT is defined as an adverse event or abnormal laboratory value. Haematological toxicity of CTCAE grade 4 for more than 4 consecutive days. Grade 3 neutropenia of any duration accompanied by fever >38.5 degrees Celsius. Grage 3 thrombocytopaenia with bleeding. Any other confirmed haematological toxicity >CTCAE grade 4. Non-haematological toxicity >CTCAE grade 3. Any other toxicity that is judged to be a DLT by the Safety Review Committee. An AE resulting in disrupted dosing >14 days.
- Module 2 - Safety and Tolerability of RXC004 in combination with Nivolumab by assessment of whether any Dose Limiting Toxicities (DLT) arise from first dose until the end of 28 days of continuous dosing [The DLT period will be assessed from the first dose until the end of 28 days of continuous dosing. This will be completed for each dose level until a Maximum Tolerated Dose (MTD) is identified. Estimated time 12 Months in total]
A DLT is defined as an adverse event or abnormal laboratory value. Haematological toxicity of CTCAE grade 4 for more than 4 consecutive days. Grade 3 neutropenia of any duration accompanied by fever >38.5 degrees Celsius. Grage 3 thrombocytopaenia with bleeding. Any other confirmed haematological toxicity >CTCAE grade 4. Non-haematological toxicity >CTCAE grade 3. Any other toxicity that is judged to be a DLT by the Safety Review Committee. An AE resulting in disrupted dosing >14 days. Any grade 3 or higher immune-related adverse events
Secondary Outcome Measures
- Module 1 [Throughout the study and at study completion (approximately 1 year)]
Characterise the PK profile of RXC004 following single dose and at steady state and after multiple dose.
- Module 2 [Throughout the study and at study completion (approximately 1 year)]
Characterise the PK profile of RXC004 in combination with Nivolumab to following single dose and at steady state and after multiple dose.
Eligibility Criteria
Criteria
(Summarized due to limitation of characters)
Inclusion Criteria:
-
Written informed consent
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Aged at least 18 years
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Histological or cytological confirmation of advanced malignancy not considered to be appropriate for further conventional treatment
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Patients must use adequate contraception measures for the duration of the study and for 6 months after the study
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Patients must have adequate organ functions
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Ability to swallow and retain oral medication
Exclusion Criteria:
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Prior treatment with a compound of the same mechanism of action as RXC004
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No other anti-cancer therapy or investigational product throughout the study
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Patients with persistent grade 2 or higher diarrhoea
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Patients at high risk of bone fractures
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QTc prolongation
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Known uncontrolled intercurrent illness
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Known severe allergies to any active or inactive ingredients
In addition for Module 2
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Patients with any contraindication/hypersensitivity to Nivolumab of excipients
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Patients with active or prior documented autoimmune of inflammatory disorders within the past 5 years
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Patients with active infections, including tuberculosis, hepatitis B, hepatitis C or human immunodeficiency virus
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Use of any live vaccines against infectious diseases (eg, influenza, varicella) within 4 weeks (28 days) of initiation of study treatment
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Patients with body weight <40kg
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Patients with a history of allogeneic organ transplant or active primary immunodeficiency
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Royal Marsden Hospital, Institute of Cancer Research | Sutton | Surrey | United Kingdom | SM2 5PT |
| 2 | Guys Hospital | London | United Kingdom | SE1 9RT | |
| 3 | The Christie NHS Foundation Trust | Manchester | United Kingdom | M20 4BX | |
| 4 | Sir Bobby Robson Cancer Trials Research Centre | Newcastle | United Kingdom | NE77DN | |
| 5 | Department of Oncology | Oxford | United Kingdom | OX3 7LE |
Sponsors and Collaborators
- Redx Pharma Plc
Investigators
- Principal Investigator: Natalie Cook, The Christie NHS Foundation Trust
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- RXC004/0001