Study to Evaluate CCS1477 in Advanced Tumours
- Conditions
- Metastatic Castration-Resistant Prostate CancerNon-small Cell Lung CancerMetastatic Breast CancerAdvanced Solid Tumors
- Interventions
- Registration Number
- NCT03568656
- Lead Sponsor
- CellCentric Ltd.
- Brief Summary
A Phase 1/2a study to assess the safety, tolerability, PK and biological activity of CCS1477 in patients with metastatic castration resistant prostate cancer, metastatic breast cancer, non-small cell lung cancer or advanced solid tumours.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 350
- Provision of consent
- ECOG performance status 0-1
- Assessable disease (by CT, MRI, bone scan or X-ray)
- Adequate organ function
- Highly effective contraception measures for duration of study
Additional inclusion criteria for mCRPC patients only:
-
Previously received abiraterone and/or enzalutamide (or equivalent anti-androgen), and docetaxel (unless ineligible or refused)
-
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
-
PSA at screening ≥2 μg/L
-
Serum testosterone concentration ≤50 ng/dL
-
Serum albumin >2.5 g/dL
Additional inclusion criteria for patients in CCS1477 plus abiraterone combination arm:
- Patients must have previously progressed on abiraterone treatment
- 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:
- Patients must have previously progressed on enzalutamide treatment
- 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 patients in mutation arm:
- Advanced solid tumour with identification of markers which may indicate potential for response to p300/CBP inhibition. Markers include loss of function mutations in CREBBP, EP300 or ARID1A, MYC gene amplifications or rearrangements and androgen receptor (AR) gene amplifications or over-expression.
- Intervention with any chemotherapy, investigational agents or other anti-cancer drugs within 14 days or 5 half-lives of the first dose
- 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
- Major surgical procedure or significant traumatic injury within 4 weeks of the first dose of study treatment
- Strong inhibitors of CYP3A4 or CYP3A4 substrates with a narrow therapeutic range taken within 2 weeks of the first dose of study treatment
- Strong inducers of CYP3A4 within 4 weeks of the first dose of study treatment
- Statins; patients should discontinue statins prior to starting study treatment
- Any unresolved reversible toxicities from prior therapy >CTCAE grade 1 at the time of starting study treatment
- Any evidence of severe or uncontrolled systemic diseases
- Any known uncontrolled inter-current illness
- QTcF prolongation (> 480 msec).
- Primary brain tumours or known or suspected brain metastases.
Additional exclusion criteria for patients in CCS1477 plus abiraterone combination arm:
- Clinically significant cardiac abnormalities
Additional exclusion criteria for patients in CCS1477 plus enzalutamide combination arm:
- History of seizures or other predisposing factors
- Use of substrates with a narrow therapeutic index metabolised by CYP2C9 or CYP2C19 within 2 weeks of the first dose of study treatment
- Clinically significant cardiac abnormalities
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description CCS1477 and enzalutamide, combination dose finding and expansion - mCRPC CCS1477 CCS1477 plus enzalutamide in patients with mCRPC CCS1477 dose escalation - mCRPC CCS1477 CCS1477 monotherapy in patients with mCRPC CCS1477 and abiraterone acetate, combination dose finding and expansion - mCRPC CCS1477 CCS1477 plus abiraterone acetate in patients with mCRPC CCS1477 expansion phase - mCRPC CCS1477 CCS1477 monotherapy in patients with mCRPC CCS1477 and enzalutamide, combination dose finding and expansion - mCRPC Enzalutamide CCS1477 plus enzalutamide in patients with mCRPC CCS1477 Monotherapy - Solid tumours CCS1477 CCS1477 expansion phase in patients with advanced solid tumours with molecular markers which may indicate potential for response to p300/CBP inhibition CCS1477 and darolutamide, combination dose finding and expansion - mCRPC CCS1477 CCS1477 plus darolutamide in patients with mCRPC CCS1477 and olaparib, combination dose finding and expansion - mCRPC and metastatic breast cancer Olaparib CCS1477 plus olaparib in patients with mCRPC or metastatic breast cancer. CCS1477 and atezolizumab, combination dose finding and expansion - non-small cell lung cancer CCS1477 CCS1477 plus atezolizumab in patients with non-small cell lung cancer CCS1477 and atezolizumab, combination dose finding and expansion - non-small cell lung cancer Atezolizumab CCS1477 plus atezolizumab in patients with non-small cell lung cancer CCS1477 and olaparib, combination dose finding and expansion - mCRPC and metastatic breast cancer CCS1477 CCS1477 plus olaparib in patients with mCRPC or metastatic breast cancer. CCS1477 and abiraterone acetate, combination dose finding and expansion - mCRPC Abiraterone acetate CCS1477 plus abiraterone acetate in patients with mCRPC CCS1477 and darolutamide, combination dose finding and expansion - mCRPC Darolutamide CCS1477 plus darolutamide in patients with mCRPC
- Primary Outcome Measures
Name Time Method Laboratory assessments Up to 12 months Clinical chemistry and haematology assessments
Incidence of treatment-related adverse events Up to 12 months Treatment-related adverse events and serious adverse events
- Secondary Outcome Measures
Name Time Method AUC of CCS1477 Up to 30 days after first dose of CCS1477 Area under the plasma concentration-time curve (AUC) from time 0 to the time of the last measurable concentration of CCS1477
PSA response Up to 12 months PSA response as defined by Prostate Cancer Clinical Trial Working Group 3 (PCWG-3)
Objective response rate (ORR) Up to 12 months * malignant soft tissue response rate (Response Evaluation Criteria in Solid Tumours \[RECIST\] v1.1)
* metastatic bone disease status (PCWG-3 bone scan criteria)CTC response Up to 12 months CTC response defined as a change from unfavourable (five or more cells) at baseline to favourable (four or fewer cells) post treatment
Radiological progression-free survival (rPFS) Up to 12 months Defined as the time from start of treatment until objective disease progression as defined by RECIST 1.1 or PCWG-3 or death
Cmax of CCS1477 Up to 30 days after first dose of CCS1477 Maximum observed plasma concentration (Cmax) of CCS1477
Trial Locations
- Locations (19)
Institute Gustave Roussy
🇫🇷Villejuif, France
Netherlands Cancer Institute (NKI)
🇳🇱Amsterdam, Netherlands
Hospital Vall d'Hebron, VHIO
🇪🇸Barcelona, Spain
START CIOCC Hospital Universitario HM
🇪🇸Madrid, Spain
Karolinska Institute
🇸🇪Stockholm, Sweden
Belfast City Hospital
🇬🇧Belfast, United Kingdom
Queen Elizabeth Hospital Cancer Centre
🇬🇧Birmingham, United Kingdom
Cambridge University Hospital
🇬🇧Cambridge, United Kingdom
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Thomas Jefferson University, Sidney Kimmel Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Institute Bergonie
🇫🇷Bordeaux, France
Hôpital Europeen Georges Pompidou
🇫🇷Paris, France
Edinburgh Cancer Centre Western General Hospital
🇬🇧Edinburgh, United Kingdom
The Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
Leicester Royal Infirmary
🇬🇧Leicester, United Kingdom
The Christie Hospital
🇬🇧Manchester, United Kingdom
Freeman Hospital
🇬🇧Newcastle, United Kingdom
University Hospital Southampton
🇬🇧Southampton, United Kingdom
Royal Marsden Hospital
🇬🇧Sutton, United Kingdom