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CancerPhase 1NCT03447470

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

A Phase 1 study testing RXC004 and Nivolumab in people with Cancer and Solid Tumor, run by Redx Pharma Ltd at 5 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cancer, Solid Tumor
What is being tested?
RXC004 and Nivolumab
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
46 participants
Where
5 sitesUnited Kingdom
Study dates
18 Mar 2019to 29 Sep 2023
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 20Show fewer
  • 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.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United Kingdom5 sites
  • Guys Hospital

    London, SE1 9RT

  • The Christie NHS Foundation Trust

    Manchester, M20 4BX

  • Sir Bobby Robson Cancer Trials Research Centre

    Newcastle, NE77DN

  • Department of Oncology

    Oxford, OX3 7LE

  • Royal Marsden Hospital, Institute of Cancer Research

    Sutton, Surrey, SM2 5PT

Other trials in United Kingdom

About this study

Official title: 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.

Read the 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.

Conditions
Cancer, Solid Tumor
Being tested
RXC004, Nivolumab
Keywords
Biliary tract cancers, Thymus cancers
Medical subject headings
Neoplasms, Biliary Tract Neoplasms, Thymus Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RXC004Drug

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

  • NivolumabDrug

    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

Study groups in NCT03447470
Study groupRoleWhat they receive
Module 1 Arm 1 - Monotherapy RXC004 (0.5 mg)ExperimentalPatients were given 0.5 mg RXC004 and monitored for Dose Limiting Toxicities.
Receives: Drug: RXC004
Module 2 Arm 1 - RXC004 (1.0 mg) plus NivolumabExperimentalPatients were given 1.0 mg RXC004 in combination with a standard dose of Nivolumab and monitored for Dose Limiting Toxicities.
Receives: Drug: RXC004; Drug: Nivolumab
Module 3 - Intermittent schedules of monotherapy RXC004ExperimentalPatients 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.
Receives: Drug: RXC004
Module 1 Arm 2 - Monotherapy RXC004 (1.0 mg)ExperimentalPatients were given 1.0 mg RXC004 and monitored for Dose Limiting Toxicities.
Receives: Drug: RXC004
Module 1 Arm 3 - Monotherapy RXC004 (1.5 mg)ExperimentalPatients were given 1.5 mg RXC004 and monitored for Dose Limiting Toxicities.
Receives: Drug: RXC004
Module 1 Arm 4 - Monotherapy RXC004 (2.0 mg)ExperimentalPatients were given 2.0 mg RXC004 and monitored for Dose Limiting Toxicities.
Receives: Drug: RXC004
Module 1 Arm 5 - Monotherapy RXC004 (3.0 mg)ExperimentalPatients were given 3.0 mg RXC004 and monitored for Dose Limiting Toxicities.
Receives: Drug: RXC004
Module 1 Arm 6 - Monotherapy RXC004 (10.0 mg)ExperimentalPatients were given 10.0 mg RXC004 and monitored for Dose Limiting Toxicities.
Receives: Drug: RXC004
Module 2 Arm 2 - RXC004 (1.5 mg) plus NivolumabExperimentalPatients were given 1.5 mg RXC004 in combination with a standard dose of Nivolumab and monitored for Dose Limiting Toxicities.
Receives: Drug: RXC004; Drug: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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:

    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.

    Measured: 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.

  2. 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.

    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

    Measured: 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

  3. Module 3 - Safety and Tolerability of RXC004 at Intermittent Dosing Schedule.

    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.

    Measured: 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 outcomes (12)
  1. Module 1 - PK Profile - AUC on Cycle 0 Day 1 (C0D1)

    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.

    Measured: Samples were analyzed from 0 - 96 hours after administration to evaluate PK parameters on Cycle 0 Day 1.

  2. Module 1 - PK Profile - C24 on Cycle 0 Day 1 (C0D1)

    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..

    Measured: Samples were analyzed from 0 - 96 hours after administration to evaluate PK parameters on Cycle 0 Day 1.

  3. Module 1 - PK Profile - Cmax on Cycle 0 Day 1 (C0D1)

    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..

    Measured: Samples were analyzed from 0 - 96 hours after administration to evaluate PK parameters on Cycle 0 Day 1.

  4. Module 1 - PK Profile - Half-life From PK Analysis on Cycle 0 Day 1 (C0D1)

    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..

    Measured: Samples were analyzed from 0 - 96 hours after administration to evaluate PK parameters on Cycle 0 Day 1.

  5. Module 2 - PK Profile - AUC on Cycle 0 Day 1 (C0D1)

    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.

    Measured: Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1.

  6. Module 2 - PK Profile - C24 on Cycle 0 Day 1 (C0D1)

    Mean Plasma concentration of RXC004 at 24 h post-dose when given in combination with Nivolumab.

    Measured: Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1.

  7. Module 2 - PK Profile - Cmax on Cycle 0 Day 1 (C0D1)

    Maximum plasma concentration (Cmax) of RXC004 following single dose on Cycle 0 Day1 when given in combination with Nivolumab..

    Measured: Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1.

  8. Module 2 - PK Profile - Half-life From PK Analysis on Cycle 0 Day 1 (C0D1)

    Half-life of RXC004 following single dose on Cycle 0 Day1 when given in combination with Nivolumab.

    Measured: Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1.

  9. Module 3 - PK Profile - AUC on Cycle 0 Day 1 (C0D1)

    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

    Measured: Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1.

  10. Module 3 - PK Profile - C24 on Cycle 0 Day 1 (C0D1)

    Mean Plasma concentration of RXC004 at 24 h post-dose

    Measured: Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1.

  11. Module 3 - PK Profile - Cmax on Cycle 0 Day 1 (C0D1)

    Maximum plasma concentration (Cmax) of RXC004 following single dose

    Measured: Samples were analyzed from 0 - 48 hours after administration to evaluate PK parameters on Cycle 0 Day 1.

  12. Module 3 - PK Profile - Half-life on Cycle 0 Day 1 (C0D1)

    Half-life of RXC004 following single dose.

    Measured: Cycle 0 Day 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Feb 2018
  2. Study start18 Mar 2019
  3. Primary completion29 Sep 2023
  4. Study completion29 Sep 2023

Resources

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
Non-randomised
Intervention model
Sequential
Model description
Module 1 monotherapy Dose escalation in those patients with advanced solid tumors while being monitored for safety and dose-limiting toxicity. This module will provide information on dosing and schedules for further module(s). Module 2 will commence by enrolling patients with advanced solid tumors into a monotherapy dose escalation, in combination with a fixed dose of nivolumab (a known anti-cancer treatment). This module will provide information and safety and tolerability of the study drug or in combination with the anti-cancer treatment. Module 3 will investigate the pharmacokinetic, Wnt pathway inhibition, incidence/severity of Wnt pathway related adverse events and anti-tumour activity of RXC004 when given at 2 different intermittent dosing schedules in selected patients with Wnt ligand dependent advanced tumours.
Masking
None (open label)
Enrolment
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03447470
Sponsor's protocol ID
RXC004/0001
Status last verified
Dec 2024
First submitted
14 Feb 2018
Last updated
29 Jan 2025
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing RXC004 and Nivolumab in people with Cancer and Solid Tumor, run by Redx Pharma Ltd at 5 sites in United Kingdom.

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 6 inclusion and 20 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: finished, as of the sponsor's last update on 29 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United Kingdom. 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?

Yes. Results are posted in the registry (first posted 29 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

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.). 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 29 Jan 2025.

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