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

Phase 1TerminatedNCT02313012

Celgene19 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Neoplasm Metastasis

Interventions

CC-90003DRUG

CC-90003 PO once daily

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (5)

Cedars Sinai Medical Center, Inflammatory Bowel Disease Center

Los Angeles, California, United States

Smilow Cancer Center

New Haven, Connecticut, United States

Levine Cancer Institute

Charlotte, North Carolina, United States

Sarah Cannon Cancer Center

Nashville, Tennessee, United States

Outcomes

Primary Outcomes

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.

Time frame: Up to 36 months

Dose Limiting Toxicities of CC-90003

Number of participants with dose limiting toxicities during the Dose Escalation Phase

Time frame: Up to 18 months

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

Time frame: Up to 36 months

Pharmacokinetics (PK) observed maximum concentration (Cmax)

The maximally observed plasma concentration of CC-90003 (Cmax)

Time frame: Cycle 1, Day 1, 2, 3 (predose), 8, 11 (predose), 15, 16, , Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation

PK-Area under the plasma concentration time curve (AUC)

Area under the plasma concentration -time curve of CC-90003

Time frame: Cycle 1, Day 1, 2, 3, (predose) 8, 11 (predose), 15, 16, Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation

PK-Time to maximal plasma concentration (Tmax)

The time to reach Cmax

Time frame: Cycle 1, Day 1, 2, 3 (predose) 8, 11 (predose), 15, 16, Cycle 2, Day 1, Cycle 3, Day 1 and at discontinuation

PK- terminal half-life; t1/2

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Secondary Outcomes

Response Rate based on RECIST 1.1

The proportion of subjects who achieve a best response of CR or PR.

Time frame: Up to 36 months

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).

Time frame: Up to 36 months

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

Time frame: Up to 36 Months

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

Time frame: Up to 36 months

Overall Survival

Overall survival is defined as the time from start of study treatment until the date of death from any cause.

Time frame: Up to 36 months