An open-label Phase I/IIa study to evaluate the safety and efficacy of CCS1477 as monotherapy and in combination, in patients with advanced solid/metastatic tumours.

Study ID: 37538
Short Title: Phase I/IIa study to evaluate CCS1477 in advanced tumours v1.0
Trust Name: UHS
Recruitment Site: Southampton General Hospital
Disease Area: Urology
Phase: II
I
Expected End Date: 31/12/2021
Postcode: SO16 6YD
Contact Name: Amanda Pattie
Contact Email: studysupport1and3.crnwessex@nihr.ac.uk
Active: Yes

Inclusion criteria, exclusion criteria and study summary

All Patients: o Provision of consent. o ECOG performance status 0-1. o Assessable disease (by CT, MRI, bone scan or X-ray). o Adequate organ functions defined as: AST/ALT < = 3 X ULN (upper limit of normal) or AST/ALT < = 5 X ULN [with underlying liver metastasis] Total bilirubin < = 1.5 X ULN Serum creatinine < = 1.5 X ULN ANC > = 1.5 x 109/L Platelets > = 100 x 109/L Haemoglobin > = 9g/dL o Highly effective contraception measures for duration of study. Additional inclusion criteria for mCRPC patients only: o Previously received abiraterone and/or enzalutamide (or equivalent anti-androgen), and docetaxel (unless ineligible or refused). o Progressive disease documented by one or more of the following: Biochemical progression defined as at least 2 stepwise increases in a series of any 3 PSA values. Progression as defined by RECIST v1.1 guideline for assessment of malignant soft tissue disease. Progression defined as two or more new metastatic bone lesions confirmed on bone scan from a previous assessment. o PSA at screening > = 2 μg/L. o Serum testosterone concentration < = 50 ng/dL. o Serum albumin > 2.5 g/dL. Additional inclusion criteria for patients in CCS1477 plus abiraterone combination arm: o Patients must have previously progressed on abiraterone treatment. o Patients whose last dose of abiraterone is greater than 6 months prior to start of study treatment will receive a 4-week run-in treatment with abiraterone to confirm refractoriness to abiraterone treatment. Additional inclusion criteria for patients in CCS1477 plus enzalutamide combination arm: o Patients must have previously progressed on enzalutamide treatment. o Patients whose last dose of enzalutamide is greater than 6 months prior to start of study treatment will receive a 4-week run-in treatment with enzalutamide to confirm refractoriness to enzalutamide treatment. Additional inclusion criteria for p300/CBP mutation expansion only: o Patients must have histological or cytological confirmation of malignancy that is advanced and not considered to be appropriate for further approved/standard of care treatment. o Confirmation that the tumour harbours one or more p300 or CBP mutations (identified locally or by a central laboratory in tumour or blood circulating free DNA).

All Patients: o Intervention with any of the following: o Any chemotherapy, investigational agents or other anti-cancer drugs within 14 days or 5 half-lives (whichever is longer of these two) of the first dose of study treatment. o Radiotherapy with a wide field of radiation or to more than 30% of the bone marrow within 4 weeks of the first dose of study treatment. o Major surgical procedure or significant traumatic injury within 4 weeks of the first dose of study treatment. o Strong inducers or inhibitors of CYP3A4, or CYP3A4 substrates with a narrow therapeutic range taken within 2 weeks of the first dose of study treatment. Herbal medications cannot be taken within 7 days of the first dose of study treatment (3 weeks for St John’s wort) or while on study treatment. o Statins; patients should discontinue statins prior to starting study treatment. o Any unresolved reversible toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment with the exception of alopecia. o Patients who are pregnant or breast-feeding at study entry. o Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). o Patients with any known uncontrolled inter-current illness including ongoing or active clinically significant infections, symptomatic congestive heart failure, hypertension, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. o QTcF prolongation (> 500 msec). o Prior malignancy that could affect compliance with the protocol or interpretation of results. o Primary brain tumours or known or suspected brain metastases. Additional exclusion criteria for patients in CCS1477 plus abiraterone combination arm: o Patients with clinically significant cardiac abnormalities as assessed by the treating physician that may include (but not limited to) recent myocardial infarction (< = 6 months) or unstable angina (< = 3 months), New York Heart association (NYHA) class III or IV heart failure except if LVEF is > = 50%, clinically significant uncontrolled rhythm disturbances, and patients with uncontrolled hypertension. Additional exclusion criteria for patients in CCS1477 plus enzalutamide combination arm: o History of seizures or other predisposing factors including, but not limited to, underlying brain injury, stroke, primary brain tumours, brain metastases and leptomeningeal disease, or alcoholism. o Use of substrates with a narrow therapeutic index metabolised by CYP2C9 or CYP2C19 within 2 weeks of the first dose of study treatment. o Patients with clinically significant cardiac abnormalities as assessed by the treating physician that may include (but not limited to) recent myocardial infarction (< = 6 months) or unstable angina (< = 3 months), New York Heart association (NYHA) class III or IV heart failure except if LVEF is > = 50%, clinically significant uncontrolled rhythm disturbances, and patients with uncontrolled hypertension.

CCS1477 is a new experimental medication (sponsored by CellCentric Ltd) for a type of prostate cancer called metastatic castration resistant prostate cancer (mCRPC). It is aimed at tumours that are not responsive to, or have become resistant to, existing medications used in late stage disease. CCS1477 may also be used for other cancers with specific gene mutations, again where existing treatments are no longer working. The purpose of this study is to examine the safety, tolerability, pharmacokinetics (PK) and efficacy of CCS1477 when treating patients with mCRPC, when given alone or in combination with other standard mCRPC therapies, and in treating patients with other solid tumour cancers which have a gene mutation in p300 or CBP. It is expected that approximately 150 patients will be recruited from up to 20 hospitals in the UK and US. The study has 5 parts consisting of dose escalation and expansion cohorts. Patients will have regular clinic visits for various safety and clinical benefit assessments, to monitor any side effects and to find out how CCS1477 is handled by the body and affects the tumour. The information gained in this study will help the sponsor to determine whether CCS1477 is suitable for further studies in humans.

Study MapList of studies

Accessibility tools

Return to header