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

Neoplasm Metastasis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02313012
• Other study ID #: CC-90003-ST-001
• Status: Terminated
• Phase: Phase 1
• Start date: January 5, 2015
• Est. completion date: May 3, 2016

Study information

• Verified date: November 2019
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 19
• Est. completion date: May 3, 2016
• Est. primary completion date: May 3, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

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

Related Conditions & MeSH terms

• Neoplasm Metastasis

Intervention

Drug:
• CC-90003
CC-90003 PO once daily

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Centre	Melbourne
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	Cedars Sinai Medical Center, Inflammatory Bowel Disease Center	Los Angeles	California
United States	Sarah Cannon Cancer Center	Nashville	Tennessee
United States	Smilow Cancer Center	New Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 36 months
Primary	Dose Limiting Toxicities of CC-90003	Number of participants with dose limiting toxicities during the Dose Escalation Phase	Up to 18 months
Primary	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	Up to 36 months
Primary	Pharmacokinetics (PK) observed maximum concentration (Cmax)	The maximally observed plasma concentration of CC-90003 (Cmax)	Cycle 1, Day 1, 2, 3 (predose), 8, 11 (predose), 15, 16, , Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation
Primary	PK-Area under the plasma concentration time curve (AUC)	Area under the plasma concentration -time curve 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
Primary	PK-Time to maximal plasma concentration (Tmax)	The time to reach Cmax	Cycle 1, Day 1, 2, 3 (predose) 8, 11 (predose), 15, 16, Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation
Primary	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	Cycle 1, Day 1, 2, 3 (predose) 8, 11 (predose), 15, 16, Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation
Primary	PK-Apparent total body clearance (CL/F)	The apparent total body clearance of CC-90003 from plasma	Cycle 1, Day 1, 2, 3 (predose) 8, 11 (predose) 15, 16, , Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation
Primary	PK- Apparent Total Volume of Distribution (Vz/F)	PK- Apparent Total Volume of Distribution (Vz/F) During the terminal phase for 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
Primary	Accumulation index of CC-90003	Accumulation represents the relationship between the dosing interval and the rate of elimination for the drug	Cycle 1, Day 1, 2, 3 (predose) 8, 11 (predose), 15, 16, Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation
Secondary	Response Rate based on RECIST 1.1	The proportion of subjects who achieve a best response of CR or PR.	Up to 36 months
Secondary	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).	Up to 36 months
Secondary	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	Up to 36 Months
Secondary	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	Up to 36 months
Secondary	Overall Survival	Overall survival is defined as the time from start of study treatment until the date of death from any cause.	Up to 36 months