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NCT Number: NCT03447470

Study to Evaluate the Safety and Tolerability of RXC004 in 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.

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Key information

Conditions

Cancer Biliary Tract Diseases Biliary Tract Neoplasms Digestive System Diseases Digestive System Neoplasms Hemic and Lymphatic Diseases Lymphatic Diseases Neoplasms Neoplasms by Site Solid Tumor Thoracic Neoplasms Thymus Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Royal Marsden Hospital, Institute of Cancer Research, Sutton, Surrey, United Kingdom

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

(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.

Treatment and study plan

RXC004

Drug

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

Nivolumab

Drug

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

Primary outcomes

  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:

    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.

  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.

    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

  3. 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.

Secondary outcomes

  1. 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.

  2. 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..

  3. 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..

  4. 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..

  5. 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.

  6. 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.

  7. 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..

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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.

Sponsors and collaborators

Lead sponsor

Redx Pharma Ltd

Industry

Registry information

Official study 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

Important dates

Study start
2019
Primary completion
2023
Study completion
2023
First posted
Feb 27, 2018
Registry last updated
Jan 29, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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