Trial | NCT03568656  Report issue

Title

Study to Evaluate CCS1477 in Advanced Tumours
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.

  • Phase

    Phase 1/Phase 2

  • Study Type

    Interventional

  • Status

    Recruiting

  • Study Participants

    350
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.
Study Started
Jul 23
2018
Primary Completion
Mar 31
2024
Anticipated
Study Completion
Mar 31
2024
Anticipated
Last Update
Sep 15
2023

Drug Olaparib

150mg tablets

Drug CCS1477

Capsules, oral

Drug Abiraterone acetate

Abiraterone acetate 500mg tablets plus prednisone/prednisolone

Drug Enzalutamide

Enzalutamide 40mg capsules/tablets

Drug Darolutamide

300mg tablets

Drug Atezolizumab

840mg/14ml concentrate for solution for infusion vials

CCS1477 dose escalation - mCRPC Experimental

CCS1477 monotherapy in patients with mCRPC

CCS1477 expansion phase - mCRPC Experimental

CCS1477 monotherapy in patients with mCRPC

CCS1477 and abiraterone acetate, combination dose finding and expansion - mCRPC Experimental

CCS1477 plus abiraterone acetate in patients with mCRPC

CCS1477 and enzalutamide, combination dose finding and expansion - mCRPC Experimental

CCS1477 plus enzalutamide in patients with mCRPC

CCS1477 Monotherapy - Solid tumours Experimental

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 Experimental

CCS1477 plus darolutamide in patients with mCRPC

CCS1477 and olaparib, combination dose finding and expansion - mCRPC and metastatic breast cancer Experimental

CCS1477 plus olaparib in patients with mCRPC or metastatic breast cancer.

CCS1477 and atezolizumab, combination dose finding and expansion - non-small cell lung cancer Experimental

CCS1477 plus atezolizumab in patients with non-small cell lung cancer

Criteria 

Inclusion Criteria:

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.

Exclusion Criteria:

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
No Results Posted