A Modular, Multi-arm, Phase 1/2a, Adaptive Design Study to Evaluate the Safety and Tolerability of RXC004, Alone and in Combination with Anti-cancer Treatments, in Patients with Advanced Malignancies
- Conditions
- Patients with Advanced MalignanciesMedDRA version: 21.0Level: LLTClassification code 10048683Term: Advanced cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-000720-98-GB
- Lead Sponsor
- Redx Pharma plc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 50
1. Ability to give written informed consent prior to any study-specific screening procedures, sampling and analyses; including access to all archival tumour tissue taken within the last 18 months, with the understanding that the consent may be withdrawn by the patient at any time without prejudice.
2. Capable of understanding the protocol requirements, is willing and able to comply with the study protocol procedures, restrictions and has signed and dated the informed consent document.
3. Patients must have histological or cytological confirmation of advanced malignancy not considered to be appropriate for further conventional treatment.
4. Aged at least 18 years at the time of screening.
5. Evaluable disease, either measurable on imaging, or with informative tumour marker(s), as assessed by RECIST 1.1 or other relevant response assessment criteria for tumour type. For RECIST 1.1, patients should have at least 1 lesion that qualifies as a RECIST 1.1 target lesion at baseline (within 28 days of the first dose). The use of scans obtained as part of standard clinical practice, prior to informed consent, will be accepted if they comply with RECIST 1.1 criteria and have been performed within the 28-day screening period.
6. Patients must have recovered from toxicities of prior therapies. (i.e. to CTCAE = grade 2) apart from alopecia.
7. Eastern Cooperative Oncology Group (ECOG) or World Health Organisation (WHO) performance status 0 or 1 with no deterioration over the previous 2 weeks and an estimated life expectancy of greater than 12 weeks.
8. Ability to swallow and retain oral medication.
9. Organ Function Requirements - Subjects must have adequate organ functions as defined below:
AST/ALT = 2X ULN (upper limit of normal; with no underlying Liver Metastasis)
AST/ALT = 3X ULN [with underlying Liver Metastasis]
Total Bilirubin within normal range
Serum Creatinine = 1.5X ULN
ANC = 1500 /µL
Platelets > 100,000/µL
Hb >9g/dL
10. Females must be using adequate contraceptive measures, must not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
Post menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
Amenorrhoeic for 12 months and serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and plasma oestradiol levels in the postmenopausal range for the institution
Module 1 Part B Monotherapy Expansion Specific Inclusion Criteria:
11. Patients must have histological or cytological confirmed, advanced or metastatic
gastric, pancreatic, colorectal or biliary cancer, not considered to be appropriate for
further conventional treatment
12. Patients in gastric, pancreatic or colorectal tumour expansion cohorts must have a
genetic alteration in the upstream Wnt signaling pathway (e.g. RNF43 mutation or
RSPO fusions). Patients in a biliary tumour expansion cohort will not have any genetic
selection.
13. Archival tumour material will be required (the provision of a fresh biopsy at screening
is also acceptable)
14. For entry into the colorectal expansion cohort patients will have a genetic alteration in
t
1. Prior therapy with a compound of the same mechanism of action as RXC004.
2. No other anti-cancer therapy or other investigational product (bisphosphonates are acceptable) is permitted other than the agent(s) described in the relevant study module
- During the study period, patients using allowed hormonal therapy should maintain a constant dose and should not change existing regimen.
- If a change in hormonal therapy is indicated, e.g. due to intolerable adverse effects, the regimen may be modified but change should be minimized thereafter.
3. Patients with persistent grade 2 or higher diarrhoea (any cause) that has not resolved or improved with appropriate treatment prior to study enrolment
4. Patients at higher risk of bone fractures, including;
• Patients with bone metastases
• Patients with beta-CTX (bone turnover marker) of > 1000 pg/mL
• Patients with Vitamin D [25(OH)D3] deficiency defined as < 30nmol/L (<12ng/mL). [Note - Patients who fail on this criteria alone can be retested within the screening window]
• Patients with a corrected total serum calcium level of <2 mmol/L and serum magnesium level of < 0.60 mmol/L
Patients with osteoporosis (as defined by a T-score of < -2.5 at L/R total hip, L/R femoral neck, or lumbar spine (L1-4) by DEXA scan) or history of fragility fractures (any fracture occurring with low-level trauma or as a result of falling < standing height and any = grade 2 vertebral fracture on VFA)
• Patients with a prior diagnosis of hyperparathyroidism, Pagets disease or Osteomalacia, considered to have no increased bone fragility risk, may be included only after consultation with the Sponsor's Medical Monitor.
• Patients who have received treatment for type 2 Diabetes Mellitus with a Thiazolidinedione peroxisome proliferator-activated receptor gamma agonist (e.g. pioglitazone or rosiglitazone) within 4 weeks prior to study drug dosing.
• Patients who have received oral or intravenous (i.v.) glucocorticoids for > 4weeks at daily doses equivalent to 7.5 mg of oral (p.o.) prednisolone within 6 weeks prior to study drug dosing
5. Patients receiving radiation to more than 30% of the bone marrow, direct radiation to their spine or pelvis, or with a wide field of radiation within 4 weeks of the first dose of study treatment.
6. Female patients who are pregnant or breast-feeding at entry
7. QTcF prolongation (> 470 msec or 60 msec above baseline)
8. Patients with any known uncontrolled inter-current illness including ongoing or active clinically significant infections, symptomatic congestive heart failure (with an Ejection Fraction (EF) = 50% or the institutional lower limit of normal whichever is lower), hypertension, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
9. Patients with any of the following medications within 4 weeks prior to enrollment:
Anti-neoplastic agents
Immunotherapy [mAbs, Interferons, Cytokines (except GCSF)]
Immunosuppressants (e.g., cyclosporin, rapamycin, tacrolimus, rituximab, alemtuzumab, natalizumab, etc.).
Another investigational drug
10. Patients with any known severe allergies (e.g., anaphylaxis) to any active or inactive ingredients in the study drugs
In addition to the core exclusion criteria, patients must not enter Module 2 if any of the following exclusion criteria are fulfilled;
11. Patients with any contraindication to the use of Nivolumab as per approved county label (Summ
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method