Neoplasm MetastasisPhase 1NCT02313012
Safety and PK Study of CC-90003 in Relapsed/Refractory Solid Tumors
A Phase 1 study testing CC-90003 in people with Neoplasm Metastasis, run by Celgene at 5 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasm Metastasis
- What is being tested?
- CC-90003
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 5 Jan 2015to 3 May 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
United States4 sites
Levine Cancer Institute
Charlotte, North Carolina, 28204
Cedars Sinai Medical Center, Inflammatory Bowel Disease Center
Los Angeles, California, 90048
Sarah Cannon Cancer Center
Nashville, Tennessee, 37203
Smilow Cancer Center
New Haven, Connecticut, 06510
About this study
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
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.
Read the 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.
- Conditions
- Neoplasm Metastasis
- Being tested
- CC-90003
- 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]
- Medical subject headings
- Neoplasm Metastasis, Recurrence, Melanoma, Thyroid Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CC-90003Drug
CC-90003 PO once daily
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: CC-90003 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 36 months
Dose Limiting Toxicities of CC-90003
Number of participants with dose limiting toxicities during the Dose Escalation Phase
Measured: 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
Measured: Up to 36 months
Pharmacokinetics (PK) observed maximum concentration (Cmax)
The maximally observed plasma concentration of CC-90003 (Cmax)
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
The proportion of subjects who achieve a best response of CR or PR.
Measured: 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).
Measured: 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
Measured: 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
Measured: 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.
Measured: Up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2014 (estimated)
- Study start5 Jan 2015
- Primary completion3 May 2016
- Study completion3 May 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neoplasm MetastasisStudies of the same condition, open and under way.
- More trials run by CelgeneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celgene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gordon Bray, MD, Study director, Celgene
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02313012
- Sponsor's protocol ID
- CC-90003-ST-001
- Status last verified
- Nov 2019
- First submitted
- 5 Dec 2014
- Last updated
- 18 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02313012
- Acronym / sponsor ID
- CC-90003-ST-001
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 19 participants (actual)
- Lead sponsor
- CelgeneIndustry (pharma, biotech, devices)
- Study start
- 5 Jan 2015 (actual)
- Primary completion
- 3 May 2016 (actual)
- Study completion
- 3 May 2016 (actual)
- First posted
- 9 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dose Level 1 CC-90003 | Experimental | Drug: CC-90003CC-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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CC-90003CC-90003 PO once daily | Drug | Dose Level 1 CC-90003 |
Primary outcome
Summary of the adverse events (type, severity, and incidence) related to CC-
Time frame: Up to 36 months
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
Time frame: Up to 18 months
Number of participants with dose limiting toxicities during the Dose Escalation Phase
Maximum Tolerated Dose (MTD) of CC-90003
Time frame: Up to 36 months
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)
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
The maximally observed plasma concentration of CC-90003 (Cmax)
PK-Area under the plasma concentration time curve (AUC)
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
Area under the plasma concentration -time curve of CC-90003
PK-Time to maximal plasma concentration (Tmax)
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
The time to reach Cmax
PK- terminal half-life; t1/2
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
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)
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
The apparent total body clearance of CC-90003 from plasma
PK- Apparent Total Volume of Distribution (Vz/F)
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- Apparent Total Volume of Distribution (Vz/F) During the terminal phase for CC- 90003
Accumulation index 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
Accumulation represents the relationship between the dosing interval and the rate of elimination for the drug
5 secondary outcomes
Response Rate based on RECIST 1.1
Time frame: Up to 36 months
Duration of Response
Time frame: Up to 36 months
Disease Control
Time frame: Up to 36 Months
Progression Free Survival
Time frame: Up to 36 months
Overall Survival
Time frame: Up to 36 months
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gordon Bray, MD study director
Celgene
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CC-90003 in people with Neoplasm Metastasis, run by Celgene at 5 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Summary of the adverse events (type, severity, and incidence) related to CC- (time frame: Up to 36 months). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2019.