Study to Evaluate CCS1477 in Advanced Tumours

January 18, 2024 updated by: CellCentric Ltd.

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.

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 Overview

Study Type

Interventional

Enrollment (Estimated)

350

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

      • Bordeaux, France, 33000
        • Completed
        • Institute Bergonie
      • Paris, France, 75015
        • Completed
        • Hopital Europeen Georges Pompidou
      • Villejuif, France, 94805
        • Completed
        • Institute Gustave Roussy
      • Amsterdam, Netherlands, 1066 CX
        • Completed
        • Netherlands Cancer Institute (NKI)
      • Rotterdam, Netherlands, 3015 GD
        • Withdrawn
        • Erasmus MC Institute
      • Barcelona, Spain, 08035
        • Completed
        • Hospital Vall d'Hebron, VHIO
      • Madrid, Spain, 28050
        • Completed
        • START CIOCC Hospital Universitario HM
      • Valencia, Spain, 46010
        • Withdrawn
        • INCLIVA Biomedical Research Institute
      • Stockholm, Sweden, 171 76
        • Completed
        • Karolinska Institute
      • Belfast, United Kingdom, BT9 7AB
        • Recruiting
        • Belfast City Hospital
        • Contact:
          • Victoria Coyle
      • Birmingham, United Kingdom, B15 2TH
        • Recruiting
        • Queen Elizabeth Hospital Cancer Centre
        • Contact:
          • Daniel Ford
      • Cambridge, United Kingdom, CB2 0QQ
        • Recruiting
        • Cambridge University Hospital
        • Contact:
          • Simon Pacey
      • Edinburgh, United Kingdom, EH4 2XU
        • Recruiting
        • Edinburgh Cancer Centre Western General Hospital
        • Contact:
          • Aravind Sundaramurthy
      • Glasgow, United Kingdom, G12 0YN
        • Recruiting
        • The Beatson West of Scotland Cancer Centre
        • Contact:
          • Richard Wilson
      • Leicester, United Kingdom, LE1 5WW
        • Recruiting
        • Leicester Royal Infirmary
        • Contact:
          • Harriet Walter
      • Manchester, United Kingdom, M20 4BX
        • Recruiting
        • The Christie Hospital
        • Contact:
          • Louise Carter
      • Newcastle, United Kingdom, NE7 7DN
        • Recruiting
        • Freeman Hospital
        • Contact:
          • Ruth Plummer
      • Southampton, United Kingdom, SO16 6YD
        • Recruiting
        • University Hospital Southampton
        • Contact:
          • Simon Crabb
      • Sutton, United Kingdom, SM2 5NG
        • Recruiting
        • Royal Marsden Hospital
        • Contact:
          • Johann de Bono
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Completed
        • Dana-Farber Cancer Institute
    • New York
      • New York, New York, United States, 10065
        • Withdrawn
        • New York-Presbyterian Hospital/Weill Cornell Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Completed
        • Thomas Jefferson University, Sidney Kimmel Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CCS1477 dose escalation - mCRPC
CCS1477 monotherapy in patients with mCRPC
Capsules, oral
Experimental: CCS1477 expansion phase - mCRPC
CCS1477 monotherapy in patients with mCRPC
Capsules, oral
Experimental: CCS1477 and abiraterone acetate, combination dose finding and expansion - mCRPC
CCS1477 plus abiraterone acetate in patients with mCRPC
Capsules, oral
Abiraterone acetate 500mg tablets plus prednisone/prednisolone
Experimental: CCS1477 and enzalutamide, combination dose finding and expansion - mCRPC
CCS1477 plus enzalutamide in patients with mCRPC
Capsules, oral
Enzalutamide 40mg capsules/tablets
Experimental: CCS1477 Monotherapy - Solid tumours
CCS1477 expansion phase in patients with advanced solid tumours with molecular markers which may indicate potential for response to p300/CBP inhibition
Capsules, oral
Experimental: CCS1477 and darolutamide, combination dose finding and expansion - mCRPC
CCS1477 plus darolutamide in patients with mCRPC
Capsules, oral
300mg tablets
Experimental: CCS1477 and olaparib, combination dose finding and expansion - mCRPC and metastatic breast cancer
CCS1477 plus olaparib in patients with mCRPC or metastatic breast cancer.
Capsules, oral
150mg tablets
Experimental: CCS1477 and atezolizumab, combination dose finding and expansion - non-small cell lung cancer
CCS1477 plus atezolizumab in patients with non-small cell lung cancer
Capsules, oral
840mg/14ml concentrate for solution for infusion vials

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of treatment-related adverse events
Time Frame: Up to 12 months
Treatment-related adverse events and serious adverse events
Up to 12 months
Laboratory assessments
Time Frame: Up to 12 months
Clinical chemistry and haematology assessments
Up to 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PSA response
Time Frame: Up to 12 months
PSA response as defined by Prostate Cancer Clinical Trial Working Group 3 (PCWG-3)
Up to 12 months
CTC response
Time Frame: 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
Up to 12 months
Objective response rate (ORR)
Time Frame: 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)
Up to 12 months
Radiological progression-free survival (rPFS)
Time Frame: 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
Up to 12 months
AUC of CCS1477
Time Frame: 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
Up to 30 days after first dose of CCS1477
Cmax of CCS1477
Time Frame: Up to 30 days after first dose of CCS1477
Maximum observed plasma concentration (Cmax) of CCS1477
Up to 30 days after first dose of CCS1477

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Johann de Bono, MD, Royal Marsden NHS Foundation Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 23, 2018

Primary Completion (Estimated)

March 1, 2024

Study Completion (Estimated)

March 1, 2024

Study Registration Dates

First Submitted

June 4, 2018

First Submitted That Met QC Criteria

June 14, 2018

First Posted (Actual)

June 26, 2018

Study Record Updates

Last Update Posted (Estimated)

January 19, 2024

Last Update Submitted That Met QC Criteria

January 18, 2024

Last Verified

April 1, 2023

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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