Study to Evaluate the Safety and Tolerability of RXC004 in Advanced Malignancies

December 18, 2024 updated by: Redx Pharma Ltd

A Modular Multi-Arm, Phase 1, Adaptive Design Study to Evaluate the Safety and Tolerability of RXC004, Alone and in Combination With Anti-cancer Treatments, in Patients With Advanced Malignancies

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Module 3: Intermittent dose schedules of RXC004 will be investigated. The intermittent schedules will utilize the module 1 dose which was shown to be safe and tolerated when used continuously. Characterisation of the PK profile; Wnt pathway inhibition; incidence/severity of Wnt pathway related AEs and anti-tumor activity will be evaluated at 2 different dosing schedules.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
46

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United Kingdom
      • London, United Kingdom, SE1 9RT
        • Guys Hospital
      • Manchester, United Kingdom, M20 4BX
        • The Christie Nhs Foundation Trust
      • Newcastle, United Kingdom, NE77DN
        • Sir Bobby Robson Cancer Trials Research Centre
      • Oxford, United Kingdom, OX3 7LE
        • Department of Oncology
    • Surrey
      • Sutton, Surrey, United Kingdom, SM2 5PT
        • Royal Marsden Hospital, Institute of Cancer Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

(Summarized due to limitation of characters)

Inclusion Criteria:

  • Written informed consent
  • Aged at least 18 years
  • Histological or cytological confirmation of advanced malignancy not considered to be appropriate for further conventional treatment
  • Patients must use adequate contraception measures for the duration of the study and for 6 months after the study
  • Patients must have adequate organ functions
  • Ability to swallow and retain oral medication

Exclusion Criteria:

  • Prior treatment with a compound of the same mechanism of action as RXC004
  • No other anti-cancer therapy or investigational product throughout the study
  • Patients with persistent grade 2 or higher diarrhoea
  • Patients at high risk of bone fractures
  • QTc prolongation
  • Known uncontrolled intercurrent illness
  • Known severe allergies to any active or inactive ingredients

In addition for Module 2

  • Patients with any contraindication/hypersensitivity to Nivolumab of excipients
  • Patients with active or prior documented autoimmune of inflammatory disorders within the past 5 years
  • Patients with active infections, including tuberculosis, hepatitis B, hepatitis C or human immunodeficiency virus
  • Use of any live vaccines against infectious diseases (eg, influenza, varicella) within 4 weeks (28 days) of initiation of study treatment
  • Patients with body weight <40kg
  • Patients with a history of allogeneic organ transplant or active primary immunodeficiency

In addition to Module 3

Patients with Wnt ligand-dependent solid tumours, defined as:

  • Biliary tract cancers
  • Thymus cancers (thymic and thymoma WHO classification)
  • Any solid tumour with documented aberration in RNF43 and/or RSPO from central pre-screening or from a recognised panel approved by the Sponsor
  • Patients willing to have mandatory skin biopsies at baseline and on one occasion while on study treatment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Module 1 Arm 1 - Monotherapy RXC004 (0.5 mg)
Patients were given 0.5 mg RXC004 and monitored for Dose Limiting Toxicities.
Drug: RXC004
RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway.
Experimental: Module 2 Arm 1 - RXC004 (1.0 mg) plus Nivolumab
Patients were given 1.0 mg RXC004 in combination with a standard dose of Nivolumab and monitored for Dose Limiting Toxicities.
Drug: RXC004
RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway.
Drug: Nivolumab

RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway.

Nivolumab is a fully human monoclonal immunoglobulin G4 antibody to PD-1
Experimental: Module 3 - Intermittent schedules of monotherapy RXC004
Patients were given 2.0 mg RXC004. The patients were treated for 2 weeks at the same dose, followed by 1 week off for a 21 day cycle.
Drug: RXC004
RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway.
Experimental: Module 1 Arm 2 - Monotherapy RXC004 (1.0 mg)
Patients were given 1.0 mg RXC004 and monitored for Dose Limiting Toxicities.
Drug: RXC004
RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway.
Experimental: Module 1 Arm 3 - Monotherapy RXC004 (1.5 mg)
Patients were given 1.5 mg RXC004 and monitored for Dose Limiting Toxicities.
Drug: RXC004
RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway.
Experimental: Module 1 Arm 4 - Monotherapy RXC004 (2.0 mg)
Patients were given 2.0 mg RXC004 and monitored for Dose Limiting Toxicities.
Drug: RXC004
RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway.
Experimental: Module 1 Arm 5 - Monotherapy RXC004 (3.0 mg)
Patients were given 3.0 mg RXC004 and monitored for Dose Limiting Toxicities.
Drug: RXC004
RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway.
Experimental: Module 1 Arm 6 - Monotherapy RXC004 (10.0 mg)
Patients were given 10.0 mg RXC004 and monitored for Dose Limiting Toxicities.
Drug: RXC004
RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway.
Experimental: Module 2 Arm 2 - RXC004 (1.5 mg) plus Nivolumab
Patients were given 1.5 mg RXC004 in combination with a standard dose of Nivolumab and monitored for Dose Limiting Toxicities.
Drug: RXC004
RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway.
Drug: Nivolumab

RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway.

Nivolumab is a fully human monoclonal immunoglobulin G4 antibody to PD-1

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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:
Time Frame: AE data was collected after each cycle and until 30-day follow-up visit after study exit. The DLT period were assessed from the first dose until the end of 21 days of continuous dosing in each cycle until a Maximum Tolerated Dose (MTD) was identified.

A DLT was defined as an adverse event or abnormal laboratory value. Haematological toxicity of CTCAE grade 4 or higher for more than 4 consecutive days.

Grade 3 neutropenia of any duration accompanied by fever 38.5 degrees Celsius or higher.

Grade 3 thrombocytopaenia with bleeding. Any other confirmed haematological toxicity CTCAE grade 4 or higher. Non-haematological toxicity CTCAE grade 3 or higher. Any other toxicity that is judged to be a DLT by the Safety Review Committee. An AE resulting in disrupted dosing >14 days.
AE data was collected after each cycle and until 30-day follow-up visit after study exit. The DLT period were assessed from the first dose until the end of 21 days of continuous dosing in each cycle until a Maximum Tolerated Dose (MTD) was identified.
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.
Time Frame: 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 or higher for more than 4 consecutive days.

Grade 3 neutropenia of any duration accompanied by fever 38.5 degrees Celsius or higher.

Grade 3 thrombocytopaenia with bleeding. Any other confirmed haematological toxicity CTCAE grade 4 or higher. Non-haematological toxicity CTCAE grade 3 or higher. 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
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
Module 3 - Safety and Tolerability of RXC004 at Intermittent Dosing Schedule.
Time Frame: The assessment period will be from the first dose until the end of 21 days of intermittent dosing or within 7 days of IP discontinuation.

Haematological toxicity of CTCAE grade 4 or higher present for more than 4 consecutive days.

Grade 3 neutropenia of any duration accompanied by fever 38.5 degrees Celsius or higher.

Grade 3 thrombocytopaenia with bleeding. Any other confirmed haematological toxicity CTCAE grade 4 or higher. Non-haematological toxicity CTCAE grade 3 or higher. 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.
The assessment period will be from the first dose until the end of 21 days of intermittent dosing or within 7 days of IP discontinuation.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Module 1 - PK Profile - AUC on Cycle 0 Day 1 (C0D1)
Time Frame: Samples were analyzed from 0 - 96 hours after administration to evaluate PK parameters on Cycle 0 Day 1.
Area under the Curve, AUC (0-24) for RXC004 was calculated from the measurement of mean plasma concentration of RXC004 at various time points from 0 - 96 hours following single dose on Cycle 0 Day1.
Samples were analyzed from 0 - 96 hours after administration to evaluate PK parameters on Cycle 0 Day 1.
Module 1 - PK Profile - C24 on Cycle 0 Day 1 (C0D1)
Time Frame: Samples were analyzed from 0 - 96 hours after administration to evaluate PK parameters on Cycle 0 Day 1.
Mean Plasma concentration of RXC004 at 24 h post-dose calculated from the measurement of mean RXC004 concentrations at various time points from 0 - 96 hours following single dose on Cycle 0 Day1..
Samples were analyzed from 0 - 96 hours after administration to evaluate PK parameters on Cycle 0 Day 1.
Module 1 - PK Profile - Cmax on Cycle 0 Day 1 (C0D1)
Time Frame: Samples were analyzed from 0 - 96 hours after administration to evaluate PK parameters on Cycle 0 Day 1.
Maximum plasma concentration (Cmax) of RXC004 following single dose calculated from the measurement of mean plasma concentration of RXC004 at various time points from 0 - 96 hours following single dose on Cycle 0 Day1..
Samples were analyzed from 0 - 96 hours after administration to evaluate PK parameters on Cycle 0 Day 1.
Module 1 - PK Profile - Half-life From PK Analysis on Cycle 0 Day 1 (C0D1)
Time Frame: Samples were analyzed from 0 - 96 hours after administration to evaluate PK parameters on Cycle 0 Day 1.
Half-life of RXC004 following single dose on Cycle 0 Day1 calculated from the measurement of mean plasma concentration of RXC004 at various time points from 0 - 96 hours following single dose on Cycle 0 Day1..
Samples were analyzed from 0 - 96 hours after administration to evaluate PK parameters on Cycle 0 Day 1.
Module 2 - PK Profile - AUC on Cycle 0 Day 1 (C0D1)
Time Frame: Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1.
AUC was calculated from the measurement of mean plasma concentration of RXC004 at various time points from 0 - 48 hours following single dose of RXC004 in combination with Nivolumab on Cycle 0 Day1.
Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1.
Module 2 - PK Profile - C24 on Cycle 0 Day 1 (C0D1)
Time Frame: Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1.
Mean Plasma concentration of RXC004 at 24 h post-dose when given in combination with Nivolumab.
Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1.
Module 2 - PK Profile - Cmax on Cycle 0 Day 1 (C0D1)
Time Frame: Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1.
Maximum plasma concentration (Cmax) of RXC004 following single dose on Cycle 0 Day1 when given in combination with Nivolumab..
Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1.
Module 2 - PK Profile - Half-life From PK Analysis on Cycle 0 Day 1 (C0D1)
Time Frame: Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1.
Half-life of RXC004 following single dose on Cycle 0 Day1 when given in combination with Nivolumab.
Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1.
Module 3 - PK Profile - AUC on Cycle 0 Day 1 (C0D1)
Time Frame: Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1.
AUC was calculated from the measurement of mean plasma concentration of RXC004 at various time points from 0 - 48 hours following single dose of RXC004
Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1.
Module 3 - PK Profile - C24 on Cycle 0 Day 1 (C0D1)
Time Frame: Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1.
Mean Plasma concentration of RXC004 at 24 h post-dose
Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1.
Module 3 - PK Profile - Cmax on Cycle 0 Day 1 (C0D1)
Time Frame: Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1.
Maximum plasma concentration (Cmax) of RXC004 following single dose
Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1.
Module 3 - PK Profile - Half-life on Cycle 0 Day 1 (C0D1)
Time Frame: Cycle 0 Day 1
Half-life of RXC004 following single dose.
Cycle 0 Day 1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Redx Pharma Ltd

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Natalie Cook, The Christie Nhs Foundation Trust

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 18, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 29, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 29, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 14, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 26, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 27, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 18, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RXC004/0001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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