Clinical trial NCT03568656: Study to Evaluate CCS1477 in Advanced Tumours
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.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Metastatic Castration-Resistant Prostate Cancer
Metastatic Breast Cancer
Non-small Cell Lung Cancer
Advanced Solid Tumors
Lead sponsor: CellCentric Ltd.
Sponsor class: INDUSTRY
First posted: 2018-06-26
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Incidence of treatment-related adverse events
timeFrame: Up to 12 months
measure: Laboratory assessments
timeFrame: Up to 12 months
Secondary outcomes:
measure: PSA response
timeFrame: Up to 12 months
measure: CTC response
timeFrame: Up to 12 months
measure: Objective response rate (ORR)
timeFrame: Up to 12 months
measure: Radiological progression-free survival (rPFS)
timeFrame: Up to 12 months
measure: AUC of CCS1477
timeFrame: Up to 30 days after first dose of CCS1477
measure: Cmax of CCS1477
timeFrame: Up to 30 days after first dose of CCS1477
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Philadelphia
country: United States
facility: Thomas Jefferson University, Sidney Kimmel Cancer Center
state: Pennsylvania
city: Bordeaux
country: France
facility: Institute Bergonie
city: Paris
country: France
facility: Hôpital Europeen Georges Pompidou
city: Villejuif
country: France
facility: Institute Gustave Roussy
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute (NKI)
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron, VHIO
city: Madrid
country: Spain
facility: START CIOCC Hospital Universitario HM
city: Stockholm
country: Sweden
facility: Karolinska Institute
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital Cancer Centre
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospital
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Centre Western General Hospital
city: Glasgow
country: United Kingdom
facility: The Beatson West of Scotland Cancer Centre
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: Manchester
country: United Kingdom
facility: The Christie Hospital
city: Newcastle
country: United Kingdom
facility: Freeman Hospital
city: Southampton
country: United Kingdom
facility: University Hospital Southampton
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
Study officials:
affiliation: Royal Marsden NHS Foundation Trust
name: Johann de Bono, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Eickhoff N, Bergman AM, Zwart W. Homing in on a Moving Target: Androgen Receptor Cistromic Plasticity in Prostate Cancer. Endocrinology. 2022 Oct 11;163(11):bqac153. doi: 10.1210/endocr/bqac153.