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Study to Evaluate CCS1477 in Advanced Tumours

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ClinicalTrials.gov Identifier: NCT03568656
Recruitment Status : Recruiting
First Posted : June 26, 2018
Last Update Posted : January 19, 2024
Sponsor:
Information provided by (Responsible Party):
CellCentric Ltd.

Study Description
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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.

Condition or disease Intervention/treatment Phase
Metastatic Castration-Resistant Prostate Cancer Metastatic Breast Cancer Non-small Cell Lung Cancer Advanced Solid Tumors Drug: CCS1477 Drug: Abiraterone acetate Drug: Enzalutamide Drug: Darolutamide Drug: Olaparib Drug: Atezolizumab Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 350 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: The RP2D/MTD dose will be determined in Part A. Parts B-H will run in parallel after the completion of Part A.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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.
Actual Study Start Date : July 23, 2018
Estimated Primary Completion Date : March 2024
Estimated Study Completion Date : March 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: CCS1477 dose escalation - mCRPC
CCS1477 monotherapy in patients with mCRPC
 Drug: CCS1477
Capsules, oral
Experimental: CCS1477 expansion phase - mCRPC
CCS1477 monotherapy in patients with mCRPC
 Drug: CCS1477
Capsules, oral
Experimental: CCS1477 and abiraterone acetate, combination dose finding and expansion - mCRPC
CCS1477 plus abiraterone acetate in patients with mCRPC
 Drug: CCS1477
Capsules, oral

Drug: Abiraterone acetate
Abiraterone acetate 500mg tablets plus prednisone/prednisolone
Experimental: CCS1477 and enzalutamide, combination dose finding and expansion - mCRPC
CCS1477 plus enzalutamide in patients with mCRPC
 Drug: CCS1477
Capsules, oral

Drug: Enzalutamide
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
 Drug: CCS1477
Capsules, oral
Experimental: CCS1477 and darolutamide, combination dose finding and expansion - mCRPC
CCS1477 plus darolutamide in patients with mCRPC
 Drug: CCS1477
Capsules, oral

Drug: Darolutamide
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.
 Drug: CCS1477
Capsules, oral

Drug: Olaparib
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
 Drug: CCS1477
Capsules, oral

Drug: Atezolizumab
840mg/14ml concentrate for solution for infusion vials


Outcome Measures
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Primary Outcome Measures :
  1. Incidence of treatment-related adverse events [ Time Frame: Up to 12 months ]
    Treatment-related adverse events and serious adverse events

  2. Laboratory assessments [ Time Frame: Up to 12 months ]
    Clinical chemistry and haematology assessments


Secondary Outcome Measures :
  1. PSA response [ Time Frame: Up to 12 months ]
    PSA response as defined by Prostate Cancer Clinical Trial Working Group 3 (PCWG-3)

  2. 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

  3. 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)

  4. 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

  5. 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

  6. Cmax of CCS1477 [ Time Frame: Up to 30 days after first dose of CCS1477 ]
    Maximum observed plasma concentration (Cmax) of CCS1477


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03568656


Contacts
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Contact: Tomasz Knurowski, MD, MFPM 07882 871299 Tomasz.Knurowski@cellcentric.com
Contact: Karen Clegg, PhD Karen.Clegg@cellcentric.com

Locations
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Sponsors and Collaborators
CellCentric Ltd.
Investigators
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Principal Investigator: Johann de Bono, MD Royal Marsden NHS Foundation Trust
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: CellCentric Ltd.
ClinicalTrials.gov Identifier: NCT03568656    
Other Study ID Numbers: CCS1477-01
First Posted: June 26, 2018    Key Record Dates
Last Update Posted: January 19, 2024
Last Verified: April 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Neoplasms by Site
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Atezolizumab
Olaparib
 Abiraterone Acetate
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Antineoplastic Agents
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 Enzyme Inhibitors