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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/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)
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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
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Secondary ID [1]
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MK-3475-E86
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Secondary ID [2]
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RXC004/0003
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Universal Trial Number (UTN)
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Trial acronym
KEYNOTE-E86
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumours
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Condition category
Condition code
Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - RXC004
Treatment: Drugs - RXC004
Treatment: Drugs - RXC004
Other interventions - Denosumab
Other interventions - 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.
Other interventions: Denosumab
Denosumab will be administered via subcutaneous (SC) injection, 120 mg once every month; Use: Prophylactic
Other interventions: pembrolizumab
Pembrolizumab will be administered via intravenous infusion, 400 mg dose once every 6 weeks
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Intervention code [1]
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Treatment: Drugs
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Intervention code [2]
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Other interventions
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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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)
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Assessment method [1]
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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.
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Timepoint [1]
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At 6 months
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Primary outcome [2]
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Combination therapy (Module 3): Objective response rate (ORR) using each patient's best overall response (BOR) according to RECIST 1.1
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Assessment method [2]
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To assess the anti-tumour activity of RXC004 as combination therapy. ORR, defined as the proportion of patients with a best overall response of complete response or partial response, based on local investigator assessment, as defined in RECIST 1.1.
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Timepoint [2]
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Up to 23 months
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Secondary outcome [1]
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Monotherapy (Modules 1 and 2): Objective Response Rate (ORR) using Investigator assessments according to RECIST 1.1
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Assessment method [1]
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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.
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Timepoint [1]
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Up to 23 months
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Secondary outcome [2]
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Monotherapy (Modules 1 and 2) and Combination therapy (Module 3): Disease Control Rate (DCR) using Investigator assessments according to RECIST 1.1
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Assessment method [2]
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To further assess the preliminary efficacy of RXC004 as monotherapy and as combination therapy. 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.
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Timepoint [2]
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Up to 23 months
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Secondary outcome [3]
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Monotherapy (Modules 1 and 2) and Combination therapy (Module 3): PFS using Investigator assessments according to RECIST 1.1
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Assessment method [3]
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To further assess the preliminary efficacy of RXC004 as monotherapy and as combination therapy. 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.
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Timepoint [3]
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Up to 23 months
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Secondary outcome [4]
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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
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Assessment method [4]
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To further assess the preliminary efficacy of RXC004 as monotherapy and as combination therapy. 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.
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Timepoint [4]
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Up to 23 months
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Secondary outcome [5]
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Monotherapy (Modules 1 and 2) and Combination therapy (Module 3): Overall survival (OS)
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Assessment method [5]
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To further assess the preliminary efficacy of RXC004 as monotherapy and as combination therapy. OS is defined as the time from first day of study treatment until death due to any cause.
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Timepoint [5]
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Up to 23 months
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Secondary outcome [6]
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Maximum observed plasma concentration (Cmax)
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Assessment method [6]
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To assess the pharmacokinetic (PK) of RXC004 as monotherapy and as combination therapy.
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Timepoint [6]
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At Cycle 0 and Cycle 1 (Each cycle is 21 days in length)
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Secondary outcome [7]
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Time to Cmax (tmax)
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Assessment method [7]
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To assess the PK of RXC004 as monotherapy and as combination therapy.
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Timepoint [7]
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At Cycle 0 and Cycle 1 (Each cycle is 21 days in length)
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Secondary outcome [8]
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Minimum observed concentration across the dosing interval (Cmin)
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Assessment method [8]
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To assess the PK of RXC004 as monotherapy and as combination therapy.
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Timepoint [8]
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At each treatment cycle (Each cycle is 21 days in length), up to 23 months
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Secondary outcome [9]
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Terminal rate constant (?z)
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Assessment method [9]
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To assess the PK of RXC004 as monotherapy and as combination therapy.
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Timepoint [9]
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At Cycle 0 and Cycle 1 (Each cycle is 21 days in length)
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Secondary outcome [10]
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Terminal half-life (t½)
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Assessment method [10]
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To assess the PK of RXC004 as monotherapy and as combination therapy.
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Timepoint [10]
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At Cycle 0 and Cycle 1 (Each cycle is 21 days in length)
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Secondary outcome [11]
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Area under the plasma concentration-time curve from zero to infinity (AUC0-8)
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Assessment method [11]
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To assess the PK of RXC004 as monotherapy and as combination therapy.
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Timepoint [11]
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At Cycle 0 and Cycle 1 (Each cycle is 21 days in length)
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Secondary outcome [12]
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Total plasma clearance after oral administration (CL/F)
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Assessment method [12]
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To assess the PK of RXC004 as monotherapy and as combination therapy.
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Timepoint [12]
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At Cycle 0 and Cycle 1 (Each cycle is 21 days in length)
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Secondary outcome [13]
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Apparent volume of distribution after oral administration (Vz/F)
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Assessment method [13]
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To assess the PK of RXC004 as monotherapy and as combination therapy.
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Timepoint [13]
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At Cycle 0 and Cycle 1 (Each cycle is 21 days in length)
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Secondary outcome [14]
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Number of patients with adverse events (AEs)
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Assessment method [14]
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To assess the safety and tolerability profile of RXC004 as monotherapy and as combination therapy.
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Timepoint [14]
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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)
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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
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
10/12/2021
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
30/11/2023
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Sample size
Target
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Accrual to date
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Final
45
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Recruitment in Australia
Recruitment state(s)
NSW,VIC
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Recruitment hospital [1]
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Wollongong Hospital - Wollongong
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Recruitment hospital [2]
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The Alfred Hospital - Alfred Health - Melbourne
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Recruitment postcode(s) [1]
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2500 - Wollongong
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Recruitment postcode(s) [2]
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3304 - Melbourne
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Recruitment outside Australia
Country [1]
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United Kingdom
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State/province [1]
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Cambridge
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Country [2]
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United Kingdom
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State/province [2]
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Glasgow
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Country [3]
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United Kingdom
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State/province [3]
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Leeds
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Country [4]
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United Kingdom
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State/province [4]
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London
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Country [5]
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United Kingdom
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State/province [5]
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Manchester
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Country [6]
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United Kingdom
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State/province [6]
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Oxford
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Country [7]
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United Kingdom
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State/province [7]
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Sheffield
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Country [8]
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United Kingdom
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State/province [8]
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Sutton
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Redx Pharma Plc
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Address
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Country
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Other collaborator category [1]
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Commercial sector/Industry
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Name [1]
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Merck Sharp & Dohme LLC
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Address [1]
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Country [1]
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Ethics approval
Ethics application status
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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.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT04907851
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/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]
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Level 7, 370 Victoria Street Darlinghurst NSW 2010
Country [1]
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Australia
Funding source category [2]
64
Commercial sector/Industry
Name [2]
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Redx Pharma Plc
Address [2]
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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]
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Australian Genomic Cancer Medicine Centre Ltd t/a Omico
Address [1]
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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]
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Research Office St Vincent’s Hospital Translational Research Centre 97-105 Boundary Street Darlinghurst NSW 2010
Country [1]
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Australia
Date submitted for ethics approval [1]
40
Approval date [1]
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18/08/2021
Ethics approval number [1]
40
Public notes
Contacts
Principal investigator
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Dr
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Name
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Lorraine Chantrill
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Address
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Head of Department Medical Oncology L3 Illawarra Cancer Care Centre Wollongong Hospital New Dapto Rd Wollongong NSW 2500
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Country
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Australia
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Phone
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+61 2 4222 5260
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Fax
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Email
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[email protected]
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Contact person for public queries
Title
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Dr
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Name
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Enmoore Lin
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Address
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The George Institute for Global Health Level 5, 1 King St Newtown NSW 2042
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Country
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Australia
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Phone
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+61 2 8052 4511
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Fax
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Email
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[email protected]
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Contact person for scientific queries
Title
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Mr
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Name
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Craig Tilston
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Address
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Redx Pharma Plc Block 33 Mereside Alderley Park Alderley Edge, Cheshire SK10 4TG
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Country
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United Kingdom
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Phone
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+44 1625 469908
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Fax
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Email
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[email protected]
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