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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02313012




Registration number
NCT02313012
Ethics application status
Date submitted
5/12/2014
Date registered
9/12/2014
Date last updated
18/11/2019

Titles & IDs
Public title
Safety and PK Study of CC-90003 in Relapsed/Refractory Solid Tumors
Scientific title
A Phase 1a Multicenter, Open-label Safety, Tolerability and Pharmacokinetic Study of CC-90003, a Selective Extracellular Signal-Regulated Kinase (ERK) Inhibitor, in Subjects With Locally-Advanced or Metastatic, Relapsed, or Refractory BRAF or RAS-Mutated Malignancies
Secondary ID [1] 0 0
CC-90003-ST-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasm Metastasis 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - CC-90003

Experimental: Dose Level 1 CC-90003 - CC-90003 by mouth (PO) daily on days 1 -21 of every 28 day cycle; Cycle 1, Days 1 to 28 will constitute the dose limiting toxicity (DLT) assessment period for purposes of non-tolerated dose (NTD) and Maximum Tolerated Dose determination.


Treatment: Drugs: CC-90003
CC-90003 PO once daily

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Summary of the adverse events (type, severity, and incidence) related to CC- - An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values regardless of etiology.
Timepoint [1] 0 0
Up to 36 months
Primary outcome [2] 0 0
Dose Limiting Toxicities of CC-90003 - Number of participants with dose limiting toxicities during the Dose Escalation Phase
Timepoint [2] 0 0
Up to 18 months
Primary outcome [3] 0 0
Maximum Tolerated Dose (MTD) of CC-90003 - The MTD is defined as the highest dose level at which no more than 1 in 6 participants experiences a dose- limiting toxicity (DLT) during the first 28 day cycle of treatment
Timepoint [3] 0 0
Up to 36 months
Primary outcome [4] 0 0
Pharmacokinetics (PK) observed maximum concentration (Cmax) - The maximally observed plasma concentration of CC-90003 (Cmax)
Timepoint [4] 0 0
Cycle 1, Day 1, 2, 3 (predose), 8, 11 (predose), 15, 16, , Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation
Primary outcome [5] 0 0
PK-Area under the plasma concentration time curve (AUC) - Area under the plasma concentration -time curve of CC-90003
Timepoint [5] 0 0
Cycle 1, Day 1, 2, 3, (predose) 8, 11 (predose), 15, 16, Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation
Primary outcome [6] 0 0
PK-Time to maximal plasma concentration (Tmax) - The time to reach Cmax
Timepoint [6] 0 0
Cycle 1, Day 1, 2, 3 (predose) 8, 11 (predose), 15, 16, Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation
Primary outcome [7] 0 0
PK- terminal half-life; t1/2 - Terminal phase elimination half-life (t1/2) is calculated as follows: t1/2 =ln(2)/?z, where ?z is the first order rate constant associated with the terminal portion of the CC-90003 plasma concentration curve
Timepoint [7] 0 0
Cycle 1, Day 1, 2, 3 (predose) 8, 11 (predose), 15, 16, Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation
Primary outcome [8] 0 0
PK-Apparent total body clearance (CL/F) - The apparent total body clearance of CC-90003 from plasma
Timepoint [8] 0 0
Cycle 1, Day 1, 2, 3 (predose) 8, 11 (predose) 15, 16, , Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation
Primary outcome [9] 0 0
PK- Apparent Total Volume of Distribution (Vz/F) - PK- Apparent Total Volume of Distribution (Vz/F) During the terminal phase for CC- 90003
Timepoint [9] 0 0
Cycle 1, Day 1, 2, 3 (predose) 8, 11 (predose), 15,16, Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation
Primary outcome [10] 0 0
Accumulation index of CC-90003 - Accumulation represents the relationship between the dosing interval and the rate of elimination for the drug
Timepoint [10] 0 0
Cycle 1, Day 1, 2, 3 (predose) 8, 11 (predose), 15, 16, Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation
Secondary outcome [1] 0 0
Response Rate based on RECIST 1.1 - The proportion of subjects who achieve a best response of CR or PR.
Timepoint [1] 0 0
Up to 36 months
Secondary outcome [2] 0 0
Duration of Response - Duration of response is the time from the start of study treatment until the first documentation of an objective response (either CR or PR).
Timepoint [2] 0 0
Up to 36 months
Secondary outcome [3] 0 0
Disease Control - The proportion of subjects who achieve a best response of SD (documented at least 56 days after the start of study treatment) PR, or CR
Timepoint [3] 0 0
Up to 36 Months
Secondary outcome [4] 0 0
Progression Free Survival - PFS is defined as the time from the start of study treatment until progression (PD) or patient death (any cause), whichever occurs first
Timepoint [4] 0 0
Up to 36 months
Secondary outcome [5] 0 0
Overall Survival - Overall survival is defined as the time from start of study treatment until the date of death from any cause.
Timepoint [5] 0 0
Up to 36 months

Eligibility
Key inclusion criteria
1. Eligible study subjects in Part 1 and Part 2 must be 18 years or older

2. Eligible study subjects must have histologic or cytologic confirmation of advanced,
unresectable or metastatic solid tumors, and have at least one measurable lesion per
Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

3. Eligible study subjects must have Eastern Cooperative Oncology Group Performance
Status (ECOG PS) of 0 or 1

4. Eligible study subjects must exhibit acceptable liver, bone marrow, renal and cardiac
functions as assessed by laboratory tests, ECG and ECHO or MUGA scan.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Subjects with symptomatic or unstable CNS metastases

2. Subjects with a history of recent (within 28 days) systemic therapy for their
underlying malignancy

3. Subjects who have had surgery/radiotherapy within 2 weeks prior to start of study

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
North Carolina
Country [4] 0 0
United States of America
State/province [4] 0 0
Tennessee

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Celgene
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The CC-90003-ST -001 trial is a first-in-man, open-label study in subjects with
locally-advanced or wide spread cancers to determine if CC-90003 (an oral medication) can be
adequately tolerated with minimal side effects.
Trial website
https://clinicaltrials.gov/show/NCT02313012
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gordon Bray, MD
Address 0 0
Celgene
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02313012