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History of Changes for Study: NCT04907851
A Study to Assess RXC004 Efficacy in Advanced Solid Tumours After Progression on Standard of Care (SoC) Therapy (PORCUPINE2)
Latest version (submitted April 28, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 May 28, 2021 None (earliest Version on record)
2 September 23, 2021 Study Status, Arms and Interventions, Contacts/Locations, Eligibility, Outcome Measures and Oversight
3 February 10, 2022 Recruitment Status, Contacts/Locations, Study Status and Study Description
4 April 28, 2022 Contacts/Locations, Study Status, Eligibility and Conditions
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Study NCT04907851
Submitted Date:  May 28, 2021 (v1)

Open or close this module Study Identification
Unique Protocol ID: RXC004/0003
Brief Title: A Study to Assess RXC004 Efficacy in Advanced Solid Tumours After Progression on Standard of Care (SoC) Therapy (PORCUPINE2)
Official Title: 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
Secondary IDs:
Open or close this module Study Status
Record Verification: May 2021
Overall Status: Not yet recruiting
Study Start: June 30, 2021
Primary Completion: July 4, 2022 [Anticipated]
Study Completion: February 4, 2023 [Anticipated]
First Submitted: May 25, 2021
First Submitted that
Met QC Criteria:
May 28, 2021
First Posted: June 1, 2021 [Actual]
Last Update Submitted that
Met QC Criteria:
May 28, 2021
Last Update Posted: June 1, 2021 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Redx Pharma Plc
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: No
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
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 safety and survival.

Open or close this module Conditions
Conditions: Advanced Solid Tumours
Keywords: Open-Label
RXC004
Ring finger protein 43
Pancreatic ductal adenocarcinoma
Biliary tract cancer
Efficacy
Safety
Pharmacokinetics
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 40 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
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 (1.5 mg once daily [QD], orally) within 6 weeks of progression following 1st line SoC treatment.
Drug: RXC004
RXC004 will be administered orally, 1.5 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
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 (1.5 mg QD, orally) within 6 weeks of progression, following 1st line SoC treatment.
Drug: RXC004
RXC004 will be administered orally, 1.5 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
Open or close this module Outcome Measures
Primary Outcome Measures:
1. 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.
Secondary Outcome Measures:
1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Core Inclusion Criteria:

  • At least one lesion that is measurable by RECIST 1.1 at baseline (within 28 days 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 RECIST1.1 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 RECIST1.1 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 4 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.
Open or close this module Contacts/Locations
Central Contact Person: Craig Tilston
Telephone: +44(0) 1625 469908
Email: c.tilston@redxpharma.com
Central Contact Backup: Richard Armer
Telephone: +44 (0)7733 361689
Email: r.armer@redxpharma.com
Locations:
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Citations:
Links:
Available IPD/Information:

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U.S. National Library of Medicine | U.S. National Institutes of Health | U.S. Department of Health & Human Services