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

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ClinicalTrials.gov Identifier: NCT03447470
Recruitment Status : Recruiting
First Posted : February 27, 2018
Last Update Posted : May 3, 2021
Sponsor:
Information provided by (Responsible Party):
Redx Pharma Plc

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.

Condition or disease Intervention/treatment Phase
Cancer Solid Tumor Drug: RXC004 Drug: Nivolumab Phase 1

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Dose escalation from 0.5mg up to 3mg, the minimum increase in dose will be 0.5mg but larger increases in dose are allowed depending in the observed exposure within a cohort
Masking: None (Open Label)
Masking Description: Open label design
Primary Purpose: Treatment
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
Actual Study Start Date : March 18, 2019
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arm Intervention/treatment
Monotherapy RXC004 - Module 1
Patients will be given RXC004 at a specified dose level and reviewed for Dose Limiting Toxicities Once the DLT period is complete RXC004 will be given at a higher dose until MTD
Drug: RXC004
RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway

Combination RXC004 plus Nivolumab - Module 2
Patients will be given RXC004 at specific doses in combination with a standard dose of Nivolumab and reviewed for Dose Limiting Toxicities Once the DLT period is complete RXC004 will be given at a higher dose until MTD
Drug: RXC004
RXC004 is taken orally, inhibits porcupine (PORCN) and interacts with the wnt signalling pathway

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




Primary Outcome Measures :
  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: The DLT period will be assessed from the first dose until the end of 21 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 for more than 4 consecutive days. Grade 3 neutropenia of any duration accompanied by fever >38.5 degrees Celsius. Grage 3 thrombocytopaenia with bleeding. Any other confirmed haematological toxicity >CTCAE grade 4. Non-haematological toxicity >CTCAE grade 3. 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 for more than 4 consecutive days. Grade 3 neutropenia of any duration accompanied by fever >38.5 degrees Celsius. Grage 3 thrombocytopaenia with bleeding. Any other confirmed haematological toxicity >CTCAE grade 4. Non-haematological toxicity >CTCAE grade 3. 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 Outcome Measures :
  1. Module 1 [ Time Frame: Throughout the study and at study completion (approximately 1 year) ]
    Characterise the PK profile of RXC004 following single dose and at steady state and after multiple dose.

  2. Module 2 [ Time Frame: Throughout the study and at study completion (approximately 1 year) ]
    Characterise the PK profile of RXC004 in combination with Nivolumab to following single dose and at steady state and after multiple dose.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

(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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03447470


Contacts
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Contact: Dr Jane Robertson CMO 44(0)1625 469900 j.robertson@redxpharma.com

Locations
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United Kingdom
Royal Marsden Hospital, Institute of Cancer Research Recruiting
Sutton, Surrey, United Kingdom, SM2 5PT
Contact: Dr Juanita Lopez         
Guys Hospital Recruiting
London, United Kingdom, SE1 9RT
Contact: Dr Debashis Sarker         
The Christie NHS Foundation Trust Recruiting
Manchester, United Kingdom, M20 4BX
Contact: Dr Natalie Cook         
Sir Bobby Robson Cancer Trials Research Centre Recruiting
Newcastle, United Kingdom, NE77DN
Contact: Dr Ruth Plummer         
Department of Oncology Recruiting
Oxford, United Kingdom, OX3 7LE
Contact: Dr Sarah Blagden         
Sponsors and Collaborators
Redx Pharma Plc
Investigators
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Principal Investigator: Natalie Cook The Christie NHS Foundation Trust
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Responsible Party: Redx Pharma Plc
ClinicalTrials.gov Identifier: NCT03447470    
Other Study ID Numbers: RXC004/0001
First Posted: February 27, 2018    Key Record Dates
Last Update Posted: May 3, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents