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A Study to Assess RXC004 Efficacy in Advanced Solid Tumours After Progression on Standard of Care (SoC) Therapy (PORCUPINE2)

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ClinicalTrials.gov Identifier: NCT04907851
Recruitment Status : Recruiting
First Posted : June 1, 2021
Last Update Posted : May 2, 2022
Sponsor:
Information provided by (Responsible Party):
Redx Pharma Plc

Tracking Information
First Submitted Date  ICMJE May 25, 2021
First Posted Date  ICMJE June 1, 2021
Last Update Posted Date May 2, 2022
Actual Study Start Date  ICMJE December 10, 2021
Estimated Primary Completion Date March 7, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 28, 2021)
Progression free survival (percent) rate at 6 months using Investigator assessment according to Response Evaluation Criteria in Solid Tumours, version 1.1 (RECIST 1.1) [ Time Frame: At 6 months ]
To assess the anti-tumour activity of RXC004. Progression free survival rate at 6 months is defined as the proportion of patients who remain alive and free of progression at 6 months.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 23, 2021)
  • Objective Response Rate (ORR) using Investigator assessments according to RECIST 1.1 [ Time Frame: Up to 20.5 months ]
    To further assess the preliminary efficacy of RXC004. ORR is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR), based on local Investigator assessment, as defined in RECIST 1.1.
  • Disease Control Rate (DCR) using Investigator assessments according to RECIST 1.1 [ Time Frame: Up to 20.5 months ]
    To further assess the preliminary efficacy of RXC004. DCR is defined as the proportion of patients with a best overall response of either CR, PR or stable disease (SD) for at least 6 weeks.
  • PFS using Investigator assessments according to RECIST 1.1 [ Time Frame: Up to 20.5 months ]
    To further assess the preliminary efficacy of RXC004. PFS is defined as the time from first dose of study treatment until the date of disease progression or death (by any cause in the absence of progression), regardless whether the patient withdraws from the assigned study treatment or receives another anticancer prior to progression.
  • Percentage change in the sum of target lesions using Investigator assessments according to RECIST 1.1 [ Time Frame: Up to 20.5 months ]
    To further assess the preliminary efficacy of RXC004. Percentage change in tumour size will be derived at each visit by the percentage change from baseline in the sum of diameters of target lesions. The best percentage change in tumour size will be the patients value representing the largest decrease (or smallest increase) from baseline in tumour size.
  • Overall survival (OS) [ Time Frame: Up to 20.5 months ]
    To further assess the preliminary efficacy of RXC004. OS is defined as the time from first day of study treatment until death due to any cause.
  • Maximum observed plasma concentration (Cmax) [ Time Frame: At Cycle 0 and Cycle 1 (Each cycle is 21 days in length) ]
    To assess the pharmacokinetic (PK) of RXC004.
  • Time to Cmax (tmax) [ Time Frame: At Cycle 0 and Cycle 1 (Each cycle is 21 days in length) ]
    To assess the PK of RXC004.
  • Minimum observed concentration across the dosing interval (Cmin) [ Time Frame: At each treatment cycle (Each cycle is 21 days in length), up to 20.5 months ]
    To assess the PK of RXC004.
  • Terminal rate constant (λz) [ Time Frame: At Cycle 0 and Cycle 1 (Each cycle is 21 days in length) ]
    To assess the PK of RXC004.
  • Terminal half-life (t½) [ Time Frame: At Cycle 0 and Cycle 1 (Each cycle is 21 days in length) ]
    To assess the PK of RXC004.
  • Area under the plasma concentration-time curve from zero to infinity (AUC0-∞) [ Time Frame: At Cycle 0 and Cycle 1 (Each cycle is 21 days in length) ]
    To assess the PK of RXC004.
  • Total plasma clearance after oral administration (CL/F) [ Time Frame: At Cycle 0 and Cycle 1 (Each cycle is 21 days in length) ]
    To assess the PK of RXC004.
  • Apparent volume of distribution after oral administration (Vz/F) [ Time Frame: At Cycle 0 and Cycle 1 (Each cycle is 21 days in length) ]
    To assess the PK of RXC004.
  • Number of patients with adverse events (AEs) [ Time Frame: From time of signature of main study informed consent form throughout the treatment period and until the 30 days after last dose of RXC004 (Up to 20.5 months) ]
    To assess the safety and tolerability profile of RXC004.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 28, 2021)
  • Objective Response Rate (ORR) using Investigator assessments according to RECIST 1.1 [ Time Frame: Up to 20 months ]
    To further assess the preliminary efficacy of RXC004. ORR is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR), based on local Investigator assessment, as defined in RECIST 1.1.
  • Disease Control Rate (DCR) using Investigator assessments according to RECIST 1.1 [ Time Frame: Up to 20 months ]
    To further assess the preliminary efficacy of RXC004. DCR is defined as the proportion of patients with a best overall response of either CR, PR or stable disease (SD) for at least 6 weeks.
  • PFS using Investigator assessments according to RECIST 1.1 [ Time Frame: Up to 20 months ]
    To further assess the preliminary efficacy of RXC004. PFS is defined as the time from first dose of study treatment until the date of disease progression or death (by any cause in the absence of progression), regardless whether the patient withdraws from the assigned study treatment or receives another anticancer prior to progression.
  • Percentage change in the sum of target lesions using Investigator assessments according to RECIST 1.1 [ Time Frame: Up to 20 months ]
    To further assess the preliminary efficacy of RXC004. Percentage change in tumour size will be derived at each visit by the percentage change from baseline in the sum of diameters of target lesions. The best percentage change in tumour size will be the patients value representing the largest decrease (or smallest increase) from baseline in tumour size.
  • Overall survival (OS) [ Time Frame: Up to 20 months ]
    To further assess the preliminary efficacy of RXC004. OS is defined as the time from first day of study treatment until death due to any cause.
  • Maximum observed plasma concentration (Cmax) [ Time Frame: At Cycle 0 and Cycle 1 (Each cycle is 21 days in length) ]
    To assess the pharmacokinetic (PK) of RXC004.
  • Time to Cmax (tmax) [ Time Frame: At Cycle 0 and Cycle 1 (Each cycle is 21 days in length) ]
    To assess the PK of RXC004.
  • Minimum observed concentration across the dosing interval (Cmin) [ Time Frame: At each treatment cycle (Each cycle is 21 days in length), up to 20 months ]
    To assess the PK of RXC004.
  • Terminal rate constant (λz) [ Time Frame: At Cycle 0 and Cycle 1 (Each cycle is 21 days in length) ]
    To assess the PK of RXC004.
  • Terminal half-life (t½) [ Time Frame: At Cycle 0 and Cycle 1 (Each cycle is 21 days in length) ]
    To assess the PK of RXC004.
  • Area under the plasma concentration-time curve from zero to infinity (AUC0-∞) [ Time Frame: At Cycle 0 and Cycle 1 (Each cycle is 21 days in length) ]
    To assess the PK of RXC004.
  • Total plasma clearance after oral administration (CL/F) [ Time Frame: At Cycle 0 and Cycle 1 (Each cycle is 21 days in length) ]
    To assess the PK of RXC004.
  • Apparent volume of distribution after oral administration (Vz/F) [ Time Frame: At Cycle 0 and Cycle 1 (Each cycle is 21 days in length) ]
    To assess the PK of RXC004.
  • Number of patients with adverse events (AEs) [ Time Frame: From time of signature of main study informed consent form throughout the treatment period and until the 30 days after last dose of RXC004 (Up to 20 months) ]
    To assess the safety and tolerability profile of RXC004.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Assess RXC004 Efficacy in Advanced Solid Tumours After Progression on Standard of Care (SoC) Therapy (PORCUPINE2)
Official Title  ICMJE A Modular, Phase II, Open-Label, Multicentre Study to Assess the Preliminary Efficacy and Safety of RXC004, in Patients With Advanced Solid Tumours That Have Progressed Following Therapy With Current Standard of Care
Brief Summary This study is to evaluate the preliminary efficacy and safety of RXC004 monotherapy in advanced solid tumours that have progressed following SoC treatment.
Detailed Description

This Phase II, modular, open label, multicentre study will initially open with ring finger protein 43 (RNF43) loss of function (LoF) mutation-positive pancreatic ductal adenocarcinoma (PDAC) (Module 1) and biliary tract cancer (BTC) (Module 2) modules. 15 evaluable patients will be enrolled in each module.

The primary objective of the study is to assess the preliminary efficacy of RXC004 in each module in terms of progression free survival (PFS) at 6 months. Following radiological progression, patients will be followed-up for survival.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumours
Intervention  ICMJE
  • Drug: RXC004
    RXC004 will be administered orally, 2 mg QD Dose Formulation: 0.5 mg or 1 mg capsules.
  • Biological: Denosumab
    Denosumab will be administered via subcutaneous (SC) injection, 120 mg once every month. Use: Prophylactic
Study Arms  ICMJE
  • Experimental: Module 1 - RNF43 Mutated Advanced (unresectable)/Metastatic Pancreatic Cancer (Stage III/IV)
    Patients (Karnofsky performance status ≥70) will be recruited and dosed with RXC004 (2 mg once daily [QD], orally) within 6 weeks of progression following 1st line SoC treatment.
    Interventions:
    • Drug: RXC004
    • Biological: Denosumab
  • Experimental: Module 2 -Advanced (unresectable)/Metastatic Biliary Tract Cancer (Stage III/IV)
    Patients (Eastern Cooperative Oncology Group [ECOG] performance status 0-1) will be recruited and dosed with RXC004 (2 mg QD, orally) within 6 weeks of progression, following 1st line SoC treatment.
    Interventions:
    • Drug: RXC004
    • Biological: Denosumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 28, 2021)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 10, 2023
Estimated Primary Completion Date March 7, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Core Inclusion Criteria:

  • At least one lesion that is measurable by RECIST 1.1 at baseline (within 6 weeks prior to start of study treatment).
  • Mandatory paired biopsies; Patients must have at least one lesion suitable for biopsy at screening
  • Adequate organ and marrow function
  • 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.

Module 1 (PDAC) Specific Inclusion Criteria

  • Histological documentation of advanced (unresectable)/metastatic (Stage III/IV) PDAC, with documented loss of function tumour mutation in RNF43
  • Patients must have received one prior systemic treatment for advanced (unresectable)/metastatic PDAC (Stage III/IV), with clear evidence of radiological disease progression
  • Patients must be enrolled and receive first dose of study treatment within 6 weeks of radiologically confirmed progression
  • Karnofsky performance status ≥70.

Module 2 (BTC) Specific Inclusion Criteria

  • Histological documentation of advanced (unresectable)/metastatic (Stage III/IV) BTC (intrahepatic or extrahepatic cholangiocarcinoma, ampulla of Vater, or gallbladder cancer)
  • Patients must have received one prior systemic treatment for advanced (unresectable)/metastatic BTC, with clear evidence of radiological disease progression
  • Patients must be enrolled and receive first dose of study treatment within 6 weeks of radiologically confirmed progression
  • ECOG status 0 or 1.

Core 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 and other investigational drugs within 3 weeks prior to the first dose of study treatment
  • Patients with a known hypersensitivity to any RXC004 excipients
  • Patients with a contra-indication for denosumab treatment
  • Patients who are pregnant or breast-feeding
  • Known active human immunodeficiency viruses (HIV), hepatitis B (HBV), or hepatitis C (HCV) infections
  • 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
  • Mean resting corrected QTcF >470 ms, obtained from triplicate ECGs performed at screening.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Craig Tilston +44(0) 1625 469908 c.tilston@redxpharma.com
Listed Location Countries  ICMJE Australia,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04907851
Other Study ID Numbers  ICMJE RXC004/0003
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Redx Pharma Plc
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Redx Pharma Plc
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Redx Pharma Plc
Verification Date April 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP