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

NCT03447470 | Completed Phase 1 Results DMC

• 1 other identifier: RXC004/0001
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 5

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.

Conditions

Cancer; Solid Tumor

Keywords

Biliary tract cancers; Thymus cancers

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  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 Outcomes (12)

• Module 1 - PK Profile - AUC on Cycle 0 Day 1 (C0D1)

  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)

  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)

  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)

  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)

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

Study Arms (9)

Module 1 Arm 1 - Monotherapy RXC004 (0.5 mg)

EXPERIMENTAL

Patients were given 0.5 mg RXC004 and monitored for Dose Limiting Toxicities.

Drug: RXC004

Module 2 Arm 1 - RXC004 (1.0 mg) plus Nivolumab

EXPERIMENTAL

Patients were given 1.0 mg RXC004 in combination with a standard dose of Nivolumab and monitored for Dose Limiting Toxicities.

Drug: RXC004; Drug: Nivolumab

Module 3 - Intermittent schedules of monotherapy RXC004

EXPERIMENTAL

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

Module 1 Arm 2 - Monotherapy RXC004 (1.0 mg)

EXPERIMENTAL

Patients were given 1.0 mg RXC004 and monitored for Dose Limiting Toxicities.

Drug: RXC004

Module 1 Arm 3 - Monotherapy RXC004 (1.5 mg)

EXPERIMENTAL

Patients were given 1.5 mg RXC004 and monitored for Dose Limiting Toxicities.

Drug: RXC004

Module 1 Arm 4 - Monotherapy RXC004 (2.0 mg)

EXPERIMENTAL

Patients were given 2.0 mg RXC004 and monitored for Dose Limiting Toxicities.

Drug: RXC004

Module 1 Arm 5 - Monotherapy RXC004 (3.0 mg)

EXPERIMENTAL

Patients were given 3.0 mg RXC004 and monitored for Dose Limiting Toxicities.

Drug: RXC004

Module 1 Arm 6 - Monotherapy RXC004 (10.0 mg)

EXPERIMENTAL

Patients were given 10.0 mg RXC004 and monitored for Dose Limiting Toxicities.

Drug: RXC004

Module 2 Arm 2 - RXC004 (1.5 mg) plus Nivolumab

EXPERIMENTAL

Patients were given 1.5 mg RXC004 in combination with a standard dose of Nivolumab and monitored for Dose Limiting Toxicities.

Drug: RXC004; Drug: Nivolumab

Interventions

RXC004 DRUG

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

Module 1 Arm 1 - Monotherapy RXC004 (0.5 mg); Module 1 Arm 2 - Monotherapy RXC004 (1.0 mg); Module 1 Arm 3 - Monotherapy RXC004 (1.5 mg); Module 1 Arm 4 - Monotherapy RXC004 (2.0 mg); Module 1 Arm 5 - Monotherapy RXC004 (3.0 mg); Module 1 Arm 6 - Monotherapy RXC004 (10.0 mg); Module 2 Arm 1 - RXC004 (1.0 mg) plus Nivolumab; Module 2 Arm 2 - RXC004 (1.5 mg) plus Nivolumab; Module 3 - Intermittent schedules of monotherapy RXC004

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

Module 2 Arm 1 - RXC004 (1.0 mg) plus Nivolumab; Module 2 Arm 2 - RXC004 (1.5 mg) plus Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Redx Pharma Ltd: lead

Study Sites (5)

Royal Marsden Hospital, Institute of Cancer Research

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Guys Hospital

London, SE1 9RT, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Sir Bobby Robson Cancer Trials Research Centre

Newcastle, NE77DN, United Kingdom

Location

Department of Oncology

Oxford, OX3 7LE, United Kingdom

Location

MeSH Terms

Conditions

Neoplasms; Biliary Tract Neoplasms; Thymus Neoplasms

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Biliary Tract Diseases; Digestive System Diseases; Thoracic Neoplasms; Lymphatic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Craig Tilston
• Organization: Redx Pharma Limited

c.tilston@redxpharma.com

+44 (0)7787 983 638

Study Officials

• Natalie Cook

  The Christie NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open label design
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 14, 2018
• First Posted: February 27, 2018
• Study Start: March 18, 2019
• Primary Completion: September 29, 2023
• Study Completion: September 29, 2023
• Last Updated: January 29, 2025
• Results First Posted: January 29, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (5)