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

Primary Purpose

Neoplasm Metastasis

Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
CC-90003
Sponsored by
Celgene
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neoplasm Metastasis focused on measuring 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]

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Cedars Sinai Medical Center, Inflammatory Bowel Disease Center
  • Smilow Cancer Center
  • Levine Cancer Institute
  • Sarah Cannon Cancer Center
  • Peter MacCallum Cancer Centre

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dose Level 1 CC-90003

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
Dose Limiting Toxicities of CC-90003
Number of participants with dose limiting toxicities during the Dose Escalation Phase
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
Pharmacokinetics (PK) observed maximum concentration (Cmax)
The maximally observed plasma concentration of CC-90003 (Cmax)
PK-Area under the plasma concentration time curve (AUC)
Area under the plasma concentration -time curve of CC-90003
PK-Time to maximal plasma concentration (Tmax)
The time to reach Cmax
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
PK-Apparent total body clearance (CL/F)
The apparent total body clearance of CC-90003 from plasma
PK- Apparent Total Volume of Distribution (Vz/F)
PK- Apparent Total Volume of Distribution (Vz/F) During the terminal phase for CC- 90003
Accumulation index of CC-90003
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
The proportion of subjects who achieve a best response of CR or PR.
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).
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
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
Overall Survival
Overall survival is defined as the time from start of study treatment until the date of death from any cause.

Full Information

First Posted
December 5, 2014
Last Updated
November 14, 2019
Sponsor
Celgene
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1. Study Identification

Unique Protocol Identification Number
NCT02313012
Brief Title
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

2. Study Status

Record Verification Date
November 2019
Overall Recruitment Status
Terminated
Study Start Date
January 5, 2015 (Actual)
Primary Completion Date
May 3, 2016 (Actual)
Study Completion Date
May 3, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celgene

4. Oversight

Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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]

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dose Level 1 CC-90003
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
CC-90003
Intervention Description
CC-90003 PO once daily
Primary Outcome Measure Information:
Title
Summary of the adverse events (type, severity, and incidence) related to CC-
Description
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
Title
Dose Limiting Toxicities of CC-90003
Description
Number of participants with dose limiting toxicities during the Dose Escalation Phase
Time Frame
Up to 18 months
Title
Maximum Tolerated Dose (MTD) of CC-90003
Description
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
Title
Pharmacokinetics (PK) observed maximum concentration (Cmax)
Description
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
Title
PK-Area under the plasma concentration time curve (AUC)
Description
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
Title
PK-Time to maximal plasma concentration (Tmax)
Description
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
Title
PK- terminal half-life; t1/2
Description
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
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
Title
PK-Apparent total body clearance (CL/F)
Description
The apparent total body clearance of CC-90003 from plasma
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
Title
PK- Apparent Total Volume of Distribution (Vz/F)
Description
PK- Apparent Total Volume of Distribution (Vz/F) During the terminal phase for 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
Title
Accumulation index of CC-90003
Description
Accumulation represents the relationship between the dosing interval and the rate of elimination for the drug
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
Secondary Outcome Measure Information:
Title
Response Rate based on RECIST 1.1
Description
The proportion of subjects who achieve a best response of CR or PR.
Time Frame
Up to 36 months
Title
Duration of Response
Description
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
Title
Disease Control
Description
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
Title
Progression Free Survival
Description
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
Title
Overall Survival
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gordon Bray, MD
Organizational Affiliation
Celgene
Official's Role
Study Director
Facility Information:
Facility Name
Cedars Sinai Medical Center, Inflammatory Bowel Disease Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Smilow Cancer Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
Levine Cancer Institute
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Sarah Cannon Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Peter MacCallum Cancer Centre
City
Melbourne
ZIP/Postal Code
3000
Country
Australia

12. IPD Sharing Statement

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

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