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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04907851


Additional trial details provided through ANZCTR are available at the end of this record.


Registration number
NCT04907851
Ethics application status
Date submitted
25/05/2021
Date registered
1/06/2021
Date last updated
8/03/2024

Titles & IDs
Public title
A Study to Assess RXC004 Efficacy in Advanced Solid Tumours After Progression on Standard of Care (SoC) Therapy (PORCUPINE2)
Scientific 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 ID [1] 0 0
MK-3475-E86
Secondary ID [2] 0 0
RXC004/0003
Universal Trial Number (UTN)
Trial acronym
KEYNOTE-E86
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumours 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - RXC004
Treatment: Drugs - RXC004
Treatment: Drugs - RXC004
Treatment: Other - Denosumab
Treatment: Other - pembrolizumab

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.

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 within 6 weeks of progression, following 1st line SoC treatment.

Experimental: Module 3-Advanced (unresectable)/Metastatic Biliary Tract Cancer (Stage Ill/IV) Combination Therapy - Patients (ECOG performance status 0-1) will be recruited and dosed with RXC004 (1.5 mg QD, orally) in combination with pembrolizumab 400 mg IV infusion every 6 weeks (q6w) within 6 weeks of progression, following 1st line Soc treatment.


Treatment: Drugs: RXC004
RXC004 will be administered orally, 2 mg QD; Dose Formulation: 0.5 mg or 1 mg capsules.

Treatment: Drugs: RXC004
RXC004 will be administered orally, 2 mg QD (Cohort 1, Module 2) and 1 mg QD (Cohort 2, Module 2); Dose Formulation: 0.5 mg or 1 mg capsules.

Treatment: Drugs: RXC004
RXC004 will be administered orally, 1.5 mg QD; Dose Formulation: 0.5 mg or 1 mg capsules.

Treatment: Other: Denosumab
Denosumab will be administered via subcutaneous (SC) injection, 120 mg once every month; Use: Prophylactic

Treatment: Other: pembrolizumab
Pembrolizumab will be administered via intravenous infusion, 400 mg dose once every 6 weeks
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Monotherapy (Modules 1 and 2): 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)
Timepoint [1] 0 0
At 6 months
Primary outcome [2] 0 0
Combination therapy (Module 3): Objective response rate (ORR) using each patient's best overall response (BOR) according to RECIST 1.1
Timepoint [2] 0 0
Up to 23 months
Secondary outcome [1] 0 0
Monotherapy (Modules 1 and 2): Objective Response Rate (ORR) using Investigator assessments according to RECIST 1.1
Timepoint [1] 0 0
Up to 23 months
Secondary outcome [2] 0 0
Monotherapy (Modules 1 and 2) and Combination therapy (Module 3): Disease Control Rate (DCR) using Investigator assessments according to RECIST 1.1
Timepoint [2] 0 0
Up to 23 months
Secondary outcome [3] 0 0
Monotherapy (Modules 1 and 2) and Combination therapy (Module 3): PFS using Investigator assessments according to RECIST 1.1
Timepoint [3] 0 0
Up to 23 months
Secondary outcome [4] 0 0
Monotherapy (Modules 1 and 2) and Combination therapy (Module 3): Percentage change in the sum of target lesions using Investigator assessments according to RECIST 1.1
Timepoint [4] 0 0
Up to 23 months
Secondary outcome [5] 0 0
Monotherapy (Modules 1 and 2) and Combination therapy (Module 3): Overall survival (OS)
Timepoint [5] 0 0
Up to 23 months
Secondary outcome [6] 0 0
Maximum observed plasma concentration (Cmax)
Timepoint [6] 0 0
At Cycle 0 and Cycle 1 (Each cycle is 21 days in length)
Secondary outcome [7] 0 0
Time to Cmax (tmax)
Timepoint [7] 0 0
At Cycle 0 and Cycle 1 (Each cycle is 21 days in length)
Secondary outcome [8] 0 0
Minimum observed concentration across the dosing interval (Cmin)
Timepoint [8] 0 0
At each treatment cycle (Each cycle is 21 days in length), up to 23 months
Secondary outcome [9] 0 0
Terminal rate constant (?z)
Timepoint [9] 0 0
At Cycle 0 and Cycle 1 (Each cycle is 21 days in length)
Secondary outcome [10] 0 0
Terminal half-life (t½)
Timepoint [10] 0 0
At Cycle 0 and Cycle 1 (Each cycle is 21 days in length)
Secondary outcome [11] 0 0
Area under the plasma concentration-time curve from zero to infinity (AUC0-8)
Timepoint [11] 0 0
At Cycle 0 and Cycle 1 (Each cycle is 21 days in length)
Secondary outcome [12] 0 0
Total plasma clearance after oral administration (CL/F)
Timepoint [12] 0 0
At Cycle 0 and Cycle 1 (Each cycle is 21 days in length)
Secondary outcome [13] 0 0
Apparent volume of distribution after oral administration (Vz/F)
Timepoint [13] 0 0
At Cycle 0 and Cycle 1 (Each cycle is 21 days in length)
Secondary outcome [14] 0 0
Number of patients with adverse events (AEs)
Timepoint [14] 0 0
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 23 months)

Eligibility
Key inclusion criteria
Core

* 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 from the time of treatment initiation, 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 and Module 3 (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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
* 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.

There are no exclusion criteria specific to Modules 1 and 2.

Module 3 Specific

* Patients with any contraindication to the use of pembrolizumab as per approved label
* Has received prior therapy with an anti-programmed cell death-1 (anti-PD-1), anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor, and was discontinued from that treatment due to a Grade 3 or higher AE
* Has received prior radiotherapy within 2 weeks of start of study treatment or have had a history of radiation pneumonitis
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of pembrolizumab in this study
* Has severe hypersensitivity (= Grade 3) to pembrolizumab and/or any of its excipients
* Has an active autoimmune disease that has required systemic treatment in past 2 years
* Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease
* Has an active infection requiring systemic therapy
* Patients with a history of allogeneic tissue/solid organ transplant
* Patients with active infections, including tuberculosis, HIV, HBV, or HCV

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
10/12/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/11/2023
Sample size
Target
Accrual to date
Final
45
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Wollongong Hospital - Wollongong
Recruitment hospital [2] 0 0
The Alfred Hospital - Alfred Health - Melbourne
Recruitment postcode(s) [1] 0 0
2500 - Wollongong
Recruitment postcode(s) [2] 0 0
3304 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United Kingdom
State/province [1] 0 0
Cambridge
Country [2] 0 0
United Kingdom
State/province [2] 0 0
Glasgow
Country [3] 0 0
United Kingdom
State/province [3] 0 0
Leeds
Country [4] 0 0
United Kingdom
State/province [4] 0 0
London
Country [5] 0 0
United Kingdom
State/province [5] 0 0
Manchester
Country [6] 0 0
United Kingdom
State/province [6] 0 0
Oxford
Country [7] 0 0
United Kingdom
State/province [7] 0 0
Sheffield
Country [8] 0 0
United Kingdom
State/province [8] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Redx Pharma Ltd
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Merck Sharp & Dohme LLC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This study is to evaluate the preliminary efficacy and safety of RXC004 monotherapy and in combination with pembrolizumab in advanced solid tumours that have progressed following SoC treatment.
Trial website
https://clinicaltrials.gov/study/NCT04907851
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04907851

Additional trial details provided through ANZCTR
Accrual to date
Recruiting in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 45
Wollongong Hospital
Recruitment postcode(s) [1] 50
2500
Funding & Sponsors
Funding source category [1] 63
Charities/Societies/Foundations
Name [1] 63
Australian Genomic Cancer Medicine Centre Ltd t/a Omico
Address [1] 63
Level 7, 370 Victoria Street Darlinghurst NSW 2010
Country [1] 63
Australia
Funding source category [2] 64
Commercial sector/Industry
Name [2] 64
Redx Pharma Plc
Address [2] 64
Block 33 Mereside, Alderley Park Alderley Edge, Cheshire SK10 4TG
Country [2] 64
United Kingdom
Primary sponsor
Commercial sector/Industry
Primary sponsor name
Redx Pharma Plc
Primary sponsor address
Block 33
Mereside, Alderley Park
Alderley Edge, Cheshire
SK10 4TG
Primary sponsor country
United Kingdom
Secondary sponsor category [1] 62
Charities/Societies/Foundations
Name [1] 62
Australian Genomic Cancer Medicine Centre Ltd t/a Omico
Address [1] 62
Level 7, 370 Victoria Street Darlinghurst NSW 2010
Country [1] 62
Australia
Ethics approval
Ethics application status
Approved
Ethics committee name [1] 40
St Vincent’s Hospital HREC
Address [1] 40
Research Office St Vincent’s Hospital Translational Research Centre 97-105 Boundary Street Darlinghurst NSW 2010
Country [1] 40
Australia
Date submitted for ethics approval [1] 40
Approval date [1] 40
18/08/2021
Ethics approval number [1] 40
 
Public notes

Contacts
Principal investigator
Title 297 0
Dr
Name 297 0
Lorraine Chantrill
Address 297 0
Head of Department Medical Oncology L3 Illawarra Cancer Care Centre Wollongong Hospital New Dapto Rd Wollongong NSW 2500
Country 297 0
Australia
Phone 297 0
+61 2 4222 5260
Fax 297 0
Email 297 0
[email protected]
Contact person for public queries
Title 298 0
Dr
Name 298 0
Enmoore Lin
Address 298 0
The George Institute for Global Health Level 5, 1 King St Newtown NSW 2042
Country 298 0
Australia
Phone 298 0
+61 2 8052 4511
Fax 298 0
Email 298 0
[email protected]
Contact person for scientific queries
Title 299 0
Mr
Name 299 0
Craig Tilston
Address 299 0
Redx Pharma Plc Block 33 Mereside Alderley Park Alderley Edge, Cheshire SK10 4TG
Country 299 0
United Kingdom
Phone 299 0
+44 1625 469908
Fax 299 0
Email 299 0
[email protected]