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

NCT02313012 | Terminated Phase 1

• 1 other identifier: CC-90003-ST-001
• Study Type: interventional
• Target: 19
• Locations: 2 countries
• Sites: 5

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.

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]

Outcome Measures

Primary Outcomes (10)

• 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

• Dose Limiting Toxicities of CC-90003

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

  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

  Up to 36 months

• 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

• 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

• 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

• PK- terminal half-life; t1/2

  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

  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 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

• 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

• 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 Outcomes (5)

• Response Rate based on RECIST 1.1

  Up to 36 months

• Duration of Response

  Up to 36 months

• Disease Control

  Up to 36 Months

• Progression Free Survival

  Up to 36 months

• Overall Survival

  Up to 36 months

Study Arms (1)

Dose Level 1 CC-90003

EXPERIMENTAL

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

Interventions

CC-90003 DRUG

CC-90003 PO once daily

Dose Level 1 CC-90003

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Celgene: lead

Study Sites (5)

Cedars Sinai Medical Center, Inflammatory Bowel Disease Center

Los Angeles, California, 90048, United States

Location

Smilow Cancer Center

New Haven, Connecticut, 06510, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Sarah Cannon Cancer Center

Nashville, Tennessee, 37203, United States

Location

Peter MacCallum Cancer Centre

Melbourne, 3000, Australia

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Recurrence; Melanoma; Thyroid Neoplasms

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Study Officials

• Gordon Bray, MD

  Celgene

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2014
• First Posted: December 9, 2014
• Study Start: January 5, 2015
• Primary Completion: May 3, 2016
• Study Completion: May 3, 2016
• Last Updated: November 18, 2019

Record last verified: 2019-11

Locations

AU (1); US (4)