Safety and PK Study of CC-90003 in Relapsed/Refractory Solid Tumors

Sponsor

Celgene (Industry)

Overall Status

Terminated

CT.gov ID

NCT02313012

Collaborator

(none)

Enrollment

Locations

Arm

15.9

Actual Duration (Months)

3.8

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Neoplasm Metastasis	Drug: CC-90003	Phase 1

Detailed Description

CC-90003-ST -001 is an open-label, multicenter, Phase 1a study in subjects with locally-advanced or metastatic, solid tumors who are intolerant of, resistant to, or have relapsed after at least one line of therapy and for whom no standard therapy exists. The study will be conducted in two parts: Dose Escalation (Part 1) and Cohort Expansion (Part 2). Subjects may continue CC-90003 until progression of their underlying malignancy, the occurrence of intolerable toxicity, or physician/subject decision to discontinue CC-90003. In Part 1, cohorts of subjects with relapsed or refractory solid tumors will receive increasing doses of CC-90003 in order to assess its safety and tolerability, the maximum tolerated dose (MTD), and PK profile. In Part 2, cohorts of subjects with specific tumors that harbor mutations involving the Mitogen -Activated Protein Kinase (MAPK) pathway will receive CC-90003 at or below the MTD until progression of disease, intolerable toxicity, or physician/subject decision to discontinue CC-90003.

Study Design

Study Type:

Interventional

Actual Enrollment :

19 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official 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

Actual Study Start Date :

Jan 5, 2015

Actual Primary Completion Date :

May 3, 2016

Actual Study Completion Date :

May 3, 2016

Arms and Interventions

Arm	Intervention/Treatment
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.	Drug: CC-90003 CC-90003 PO once daily

Arm

Intervention/Treatment

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.

Drug: CC-90003

CC-90003 PO once daily

Outcome Measures

Primary Outcome Measures

Summary of the adverse events (type, severity, and incidence) related to CC- [Up to 36 months]
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.
Dose Limiting Toxicities of CC-90003 [Up to 18 months]
Number of participants with dose limiting toxicities during the Dose Escalation Phase
Maximum Tolerated Dose (MTD) of CC-90003 [Up to 36 months]
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
Pharmacokinetics (PK) observed maximum concentration (Cmax) [Cycle 1, Day 1, 2, 3 (predose), 8, 11 (predose), 15, 16, , Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation]
The maximally observed plasma concentration of CC-90003 (Cmax)
PK-Area under the plasma concentration time curve (AUC) [Cycle 1, Day 1, 2, 3, (predose) 8, 11 (predose), 15, 16, Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation]
Area under the plasma concentration -time curve of CC-90003
PK-Time to maximal plasma concentration (Tmax) [Cycle 1, Day 1, 2, 3 (predose) 8, 11 (predose), 15, 16, Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation]
The time to reach Cmax
PK- terminal half-life; t1/2 [Cycle 1, Day 1, 2, 3 (predose) 8, 11 (predose), 15, 16, Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation]
Terminal phase elimination half-life (t1/2) is calculated as follows: t1/2 =ln(2)/λz, where λz is the first order rate constant associated with the terminal portion of the CC-90003 plasma concentration curve
PK-Apparent total body clearance (CL/F) [Cycle 1, Day 1, 2, 3 (predose) 8, 11 (predose) 15, 16, , Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation]
The apparent total body clearance of CC-90003 from plasma
PK- Apparent Total Volume of Distribution (Vz/F) [Cycle 1, Day 1, 2, 3 (predose) 8, 11 (predose), 15,16, Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation]
PK- Apparent Total Volume of Distribution (Vz/F) During the terminal phase for CC- 90003
Accumulation index of CC-90003 [Cycle 1, Day 1, 2, 3 (predose) 8, 11 (predose), 15, 16, Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation]
Accumulation represents the relationship between the dosing interval and the rate of elimination for the drug

Secondary Outcome Measures

Response Rate based on RECIST 1.1 [Up to 36 months]
The proportion of subjects who achieve a best response of CR or PR.
Duration of Response [Up to 36 months]
Duration of response is the time from the start of study treatment until the first documentation of an objective response (either CR or PR).
Disease Control [Up to 36 Months]
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
Progression Free Survival [Up to 36 months]
PFS is defined as the time from the start of study treatment until progression (PD) or patient death (any cause), whichever occurs first
Overall Survival [Up to 36 months]
Overall survival is defined as the time from start of study treatment until the date of death from any cause.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Eligible study subjects in Part 1 and Part 2 must be 18 years or older
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
Eligible study subjects must have Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
Eligible study subjects must exhibit acceptable liver, bone marrow, renal and cardiac functions as assessed by laboratory tests, ECG and ECHO or MUGA scan.

Exclusion Criteria:

Subjects with symptomatic or unstable CNS metastases
Subjects with a history of recent (within 28 days) systemic therapy for their underlying malignancy
Subjects who have had surgery/radiotherapy within 2 weeks prior to start of study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedars Sinai Medical Center, Inflammatory Bowel Disease Center	Los Angeles	California	United States	90048
2	Smilow Cancer Center	New Haven	Connecticut	United States	06510
3	Levine Cancer Institute	Charlotte	North Carolina	United States	28204
4	Sarah Cannon Cancer Center	Nashville	Tennessee	United States	37203
5	Peter MacCallum Cancer Centre	Melbourne		Australia	3000