Clinical trial NCT02313012: Safety and PK Study of CC-90003 in Relapsed/Refractory Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Neoplasm Metastasis
Keywords: Maximum Tolerated Dose
Solid Tumors
Locally Advanced Tumors
Metastatic Solid Tumors
Relapsed or refractory, BRAFV600 or RAS-mutated solid tumors
Melanoma
Colorectal Carcinomas Papillary
Thyroid carcinomas
Pancreatic ductal Adenocarcinomas
Non -small cell lung cancer [NSCLC]
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2014-12-09
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Summary of the adverse events (type, severity, and incidence) related to CC-
timeFrame: Up to 36 months
measure: Dose Limiting Toxicities of CC-90003
timeFrame: Up to 18 months
measure: Maximum Tolerated Dose (MTD) of CC-90003
timeFrame: Up to 36 months
measure: Pharmacokinetics (PK) observed maximum concentration (Cmax)
timeFrame: Cycle 1, Day 1, 2, 3 (predose), 8, 11 (predose), 15, 16, , Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation
measure: PK-Area under the plasma concentration time curve (AUC)
timeFrame: Cycle 1, Day 1, 2, 3, (predose) 8, 11 (predose), 15, 16, Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation
measure: PK-Time to maximal plasma concentration (Tmax)
timeFrame: Cycle 1, Day 1, 2, 3 (predose) 8, 11 (predose), 15, 16, Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation
measure: PK- terminal half-life; t1/2
timeFrame: Cycle 1, Day 1, 2, 3 (predose) 8, 11 (predose), 15, 16, Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation
measure: PK-Apparent total body clearance (CL/F)
timeFrame: Cycle 1, Day 1, 2, 3 (predose) 8, 11 (predose) 15, 16, , Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation
measure: PK- Apparent Total Volume of Distribution (Vz/F)
timeFrame: Cycle 1, Day 1, 2, 3 (predose) 8, 11 (predose), 15,16, Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation
measure: Accumulation index of CC-90003
timeFrame: Cycle 1, Day 1, 2, 3 (predose) 8, 11 (predose), 15, 16, Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation
Secondary outcomes:
measure: Response Rate based on RECIST 1.1
timeFrame: Up to 36 months
measure: Duration of Response
timeFrame: Up to 36 months
measure: Disease Control
timeFrame: Up to 36 Months
measure: Progression Free Survival
timeFrame: Up to 36 months
measure: Overall Survival
timeFrame: Up to 36 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center, Inflammatory Bowel Disease Center
state: California
city: New Haven
country: United States
facility: Smilow Cancer Center
state: Connecticut
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Nashville
country: United States
facility: Sarah Cannon Cancer Center
state: Tennessee
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
Study officials:
affiliation: Celgene
name: Gordon Bray, MD
role: STUDY_DIRECTOR
References: