A first in human study to investigate the safety and tolerability of CV6-168 in combination with anti-cancer treatments in patients with advanced cancer.
- Conditions
- CancerAdvanced malignancies
- Registration Number
- ISRCTN12434145
- Lead Sponsor
- CV6 Therapeutics (NI) Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 141
Module 1 Inclusion Criteria: Inclusion Criteria for Part A (Dose Escalation) & Part B (Dose Expansion)
To be eligible for inclusion into this study, each patient must fulfil the following inclusion criteria within 28 days before C1D1:
1. Patients must be aged at least 18 years.
2. An ECOG Performance Score of 0-1.
3. A life expectancy of at least 12 weeks.
4. Patients must be able to swallow oral medications.
5. Women of childbearing potential (WOCBP) must have a negative serum test (minimum sensitivity 25 IU/L or equivalent units of HCG) during screening and within 48 hours prior to the start of investigational product and agree to have regular urine pregnancy testing throughout the trial. WOCBP must agree to use two effective forms of contraception (one highly effective form plus a barrier method) throughout the study and until 6 months after the last study medication administration. A woman is considered as WOCBP, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. Post-menopause is defined as:
5.1. Amenorrhea = 12 consecutive months without another cause, or
5.2. For women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level >35 mIU/mL; however, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
5.3. For women who have had surgical bilateral oophorectomy (with or without hysterectomy) at least 6 weeks before screening. In the case of bilateral oophorectomy alone, the female patient is considered of non-childbearing potential only when the reproductive status of the patient has been confirmed by FSH hormone level assessment.
6. Male patients must agree to use a barrier method of contraception [condom plus spermicide] and refrain from donating sperm from the first administration of IMP, throughout the study and until 6 months after the last IMP administration. Men with partners of child-bearing potential must also be willing to ensure that their partner uses a highly effective method of contraception for the same duration. Men with pregnant or lactating partners should be advised to use barrier method contraception (e.g., condom plus spermicidal gel) to prevent exposure to the foetus or neonate.
7. Histological or cytological diagnosis of malignancy.
8. Clinical or pathological diagnosis of an advanced disease.
9. Adequate bone marrow function as defined by:
9.1. Absolute neutrophil count (ANC) =1.5 × 109/L
9.2. Platelet count =100 × 109/L
9.3. Haemoglobin =9 g/dL (transfusion allowed to achieve this but must be stable afterwards).
10. Adequate hepatic function as evidenced by a serum bilirubin =1.5X the upper limit of the normal range (ULN) (unless due to Gilbert’s syndrome in which case up to 3 × ULN is permissible) and serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels =2.5X the ULN for the reference lab (=5X the ULN if there is evidence of hepatic involvement by malignant disease).
11. Adequate renal function assessed as glomerular filtration rate =50 mL/min (calculated by the Cockcroft-Gault method).
12. Serum albumin =30 g/L.
13. Patients must have been advised to take measures to avoid or minimize exposure to UV light for the duration of study participation and for a period of 4 weeks following the last dose of study medication.
14. P
Module 1 Exclusion Criteria: Exclusion Criteria for Part A (Dose Escalation) & Part B (Dose Expansion)
To be eligible for inclusion into this study, each patient must violate none of the following exclusion criteria within 28 days before C1D1:
1. Patients who received treatment for the malignancy within 28 days before the first dose of IMP.
2. Patients with an active bacterial or viral infection (including Severe Acute Respiratory Syndrome Coronavirus 2 [SARS-CoV-2], Herpes Zoster, Varicella Zoster or chickenpox), including a major systemic infection requiring antibiotics or antivirals 1 week or less prior to the first dose of study drug.
3. Patients with known active hepatitis B or C (mandatory testing not required).
4. Patients with known Human Immunodeficiency Virus (HIV) infection (mandatory testing not required).
5. Patients with any other condition, including mental illness or substance abuse or abnormal laboratory results, deemed by the Investigator to be likely to interfere with a patient’s ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results. This includes (but is not limited to) the following:
5.1. Congestive heart failure (New York Heart Association Class III or Class IV).
5.2. Clinically significant coronary heart disease or myocardial infarction within 6 months of the first dose of study medication or high risk of uncontrolled arrhythmia.
5.3. Unstable or poorly controlled angina pectoris.
5.4. Complete left bundle branch, fascicular block or other clinically significant abnormal ECG finding.
5.5. QTc interval >470 milliseconds using the Fridericia formula.
5.6. History of or current risk factor for torsade de pointes (e.g., heart failure, hypokalaemia, or a family history of long QT syndrome).
5.7. History of severe skin reactions.
5.8. History of severe ocular disorders.
5.9. Interstitial pneumonitis or pulmonary fibrosis.
5.10. Diabetes mellitus with ketoacidosis or chronic obstructive pulmonary disease (COPD) requiring hospitalisation in the preceding 6 months; or any other intercurrent medical condition that contra-indicates treatment with CV6-168 or places the patient at undue risk for treatment-related complications.
6. Female patients who are pregnant or breastfeeding.
7. Patients who have had any active bleeding in the last = 4 weeks or have an otherwise known bleeding diathesis.
8. History of hypersensitivity or current contra-indications or severe toxicity to 5-FU (irrespective of DPYD polymorphism status), FUdR or capecitabine.
9. Evidence of central nervous system (CNS) or leptomeningeal metastases.
10. Palliative radiotherapy during participation in the study is permitted but should not be concurrent with study treatment and recovery should be allowed to prevent overlapping toxicity. It should not include a target lesion.
11. No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, curatively treated in situ cancer of the cervix, surgically excised or potentially curatively treated ductal carcinoma in situ of the breast or potentially curatively treated in situ melanoma, superficial bladder cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for at least 3 years.
12. Thromboembolic event in the 6 months before inclusion (e.g., transitory ischemic st
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method