Trial purpose
Cancer treatment
Tumor type
Upper gastrointestinal tract
Age
18+
Clinical summary
Summary
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. All participants will receive RXC004 (2mg daily, orally). Denosumab will also be administered via subcutaneous injection at a dose of 120mg once a month.
Conditions
This trial is treating people with RNF43 mutated or metastatic pancreatic cancer and biliary tract cancer
Eligibility
Inclusion
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 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.
Exclusion
- 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 Exclusion Criteria:
- 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
Inclusion
- Your cancer has spread to other parts of the body (metastatic) or has grown into nearby parts of the body (locally advanced).
- Your cancer has not spread to other parts of the body (localised).
- You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.
Exclusion
- You have certain types of non-cancer medical conditions.
- You have had certain treatments, surgical procedures or drugs.
- You are currently being treated on a clinical trial.
Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.
More information
Trial Identifiers
Information on this page is partially produced from ClinicalTrials.gov *. View further details about this trial on the registry via the links below:
Trial sponsor
Redx Pharma Plc
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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