A Study to Assess Efficacy of RXC004 +/- Nivolumab in Ring Finger Protein 43 (RNF43) or R-spondin (RSPO) Aberrated, Metastatic, Microsatellite Stable, Colorectal Cancer After Progression on Standard of Care (SOC)

NCT ID: NCT04907539

Last Updated: 2025-04-16

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

25 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-11-08

Study Completion Date

2024-04-02

Brief Summary

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This is a Phase II, open label, multicentre, multi-arm, study to evaluate the preliminary efficacy and safety of RXC004 as monotherapy and in combination with nivolumab in patients with Ring finger protein 43 (RNF43) or R-spondin (RSPO) aberrated, microsatellite stable (MSS), colorectal cancer (CRC), that have progressed following current standard of care treatment.

Detailed Description

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The study is composed of two arms, RXC004 monotherapy (Arm A) and RXC004 in combination with nivolumab (Arm B). 20 evaluable patients will be enrolled in Arm A and 20 eligible patients in Arm B.

The study initially opened with Arm A; Arm B will be opened once a recommended Phase II dose (RP2D) for RXC004 in combination with nivolumab is established in the phase I dose escalation study (NCT03447470).

Once Arm B is opened, patients who are eligible for both Arm A and Arm B will be randomised 2:1 to Arm B: Arm A in an open-label manner.

Patients in Arm A may be treated with RXC004 + nivolumab if they have progressive disease on the 8 week scan, as long as they are eligible for Arm B and have Sponsor approval.

Conditions

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Colorectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A: RXC004 monotherapy

Patients will receive RXC004 (2 mg once daily \[QD\], orally).

Patients in Arm A may crossover to Arm B treatment if they have progressive disease on the first Response Evaluation Criteria in Solid Tumours, (RECIST) scan (if Arm B is open at the time of progression).

Group Type EXPERIMENTAL

RXC004

Intervention Type DRUG

RXC004 will be administered orally, 2 mg QD (Monotherapy); and 1.5 mg QD (Combination therapy)

Dose Formulation: 0.5 mg or 1 mg capsules.

Denosumab

Intervention Type BIOLOGICAL

Denosumab will be administered via subcutaneous (SC) injection, 120 mg once every month.

Use: Prophylactic

Arm B: RXC004 + nivolumab

Patients will receive RXC004 (1.5 mg QD, orally) in combination with nivolumab (480 mg every 4 weeks \[q4w\], intravenous \[IV\] infusion).

Arm B will be opened once a RP2D for RXC004 in combination with nivolumab is established in the phase I dose escalation study (NCT03447470). RXC004 dose to be used in combination with nivolumab will be based on data from the phase 1 study (NCT03447470).

Group Type EXPERIMENTAL

RXC004

Intervention Type DRUG

RXC004 will be administered orally, 2 mg QD (Monotherapy); and 1.5 mg QD (Combination therapy)

Dose Formulation: 0.5 mg or 1 mg capsules.

Nivolumab

Intervention Type BIOLOGICAL

Nivolumab will be administered via IV infusion, 480 mg q4w.

Denosumab

Intervention Type BIOLOGICAL

Denosumab will be administered via subcutaneous (SC) injection, 120 mg once every month.

Use: Prophylactic

Interventions

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RXC004

RXC004 will be administered orally, 2 mg QD (Monotherapy); and 1.5 mg QD (Combination therapy)

Dose Formulation: 0.5 mg or 1 mg capsules.

Intervention Type DRUG

Nivolumab

Nivolumab will be administered via IV infusion, 480 mg q4w.

Intervention Type BIOLOGICAL

Denosumab

Denosumab will be administered via subcutaneous (SC) injection, 120 mg once every month.

Use: Prophylactic

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* Histological documentation of metastatic (Stage IV) Colorectal cancer (CRC) and

1. Documented tumour tissue aberration in RNF43 and/or RSPO
2. Documented confirmation of microsatellite stable (MSS) status
* Patients must have had documented radiological progression following a minimum of 1 prior SOC treatment regimen for metastatic disease
* Eastern Cooperative Oncology Group performance status 0 or 1
* At least one lesion that is measurable by RECIST 1.1 at baseline
* Patients must have at least one lesion suitable for biopsy at screening and be willing to provide mandatory tumour biopsy samples
* Patients with adequate organ functions
* Female patients of childbearing potential must have a negative pregnancy test prior to start of dosing
* Female patients of childbearing potential and male patients with female partners of childbearing potential must agree to use a highly effective method of contraception during the study and for at least 5 months after the last dose of study drug.


* Patients must have had documented RECIST1.1 defined radiological progression on RXC004 monotherapy treatment on the first scheduled scan (week 8 +/- 1 week)
* Patients must receive Cycle 1 Day 1 of combination study treatment within 28 days of the first scheduled scan (week 8 +/- 1 week).

Exclusion Criteria

* Prior therapy with a compound of the same mechanism of action as RXC004
* Patients at higher risk of bone fractures
* Any known uncontrolled inter-current illness or persistent clinically significant toxicity related to prior anti-cancer treatment
* Patients who have any history of an active (requiring treatment) other malignancy within 2 years of study entry
* Patients with known or suspected brain metastases
* Use of anti-neoplastic agents, immunosuppressants and other investigational drugs
* Patients with a known hypersensitivity to any RXC004 excipients
* Patients with a contra-indication for denosumab treatment
* Patients who are pregnant or breast-feeding
* Use of any live or live-attenuated vaccines against infectious diseases (e.g., influenza nasal spray, varicella) within 4 weeks (28 days) of initiation of study treatment
* Patients with a mean resting corrected QTcF \>470 ms, obtained from triplicate electrocardiograms performed at screening

For patients on RXC004 + nivolumab combination treatment (Arm B or Arm A RXC004 + nivolumab treatment phase):

* Patients with any contraindication to the use of nivolumab
* Patients with active or prior documented autoimmune or inflammatory disorders within the past 5 years
* Patients with active infections, including tuberculosis, hepatitis B, hepatitis C or human immunodeficiency virus
* Patients with a history of allogeneic organ transplant or active primary immunodeficiency
* Patients with a known hypersensitivity to nivolumab or any of the excipients of the product
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Redx Pharma Ltd

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Providence Medical Foundation

Santa Rosa, California, United States

Site Status

Community Health Network Cancer Center North - Community Hospital Network

Indianapolis, Indiana, United States

Site Status

OptumCare Cancer Care

Las Vegas, Nevada, United States

Site Status

UT MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Lumi Research

Kingswood, Texas, United States

Site Status

National Cancer Center

Goyang-si, Gyeonggido [Kyonggi-do], South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Severance Hospital, Yonsei University Health System - Medical Oncology

Seoul, , South Korea

Site Status

Asan Medical Center - Oncology

Seoul, , South Korea

Site Status

Samsung Medical Center - Hematology-Oncology

Seoul, , South Korea

Site Status

Hospital del Mar

Barcelona, , Spain

Site Status

Hospital Universitario Vall d'Hebrón

Barcelona, , Spain

Site Status

Hospital Clìnic de Barcelona

Barcelona, , Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Hospital Universitario Virgen del Rocio

Seville, , Spain

Site Status

Beatson West of Scotland Cancer Centre - Oncology

Glasgow, Scotland, United Kingdom

Site Status

Queen Elizabeth Hospital - Clinical Reasearch

Birmingham, , United Kingdom

Site Status

University College of London (UCL)

London, , United Kingdom

Site Status

The Royal Marsden NHS Foundation Trust - Royal Marsden Hospital

London, , United Kingdom

Site Status

Christie Hospital

Manchester, , United Kingdom

Site Status

Oxford Cancer Centre

Oxford, , United Kingdom

Site Status

The Royal Marsden Hospital (Surrey)

Surrey Quays, , United Kingdom

Site Status

Countries

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United States South Korea Spain United Kingdom

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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RXC004/0002

Identifier Type: -

Identifier Source: org_study_id

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