Carcinoma, Non-Small-Cell LungPhase 1NCT01545947
Study Assessing Safety, Pharmacokinetics and Efficacy of CC-223 With Either Erlotinib or Oral Azacitidine in Advanced Non-Small Cell Lung Cancer
A Phase 1 study testing CC-223, erlotinib and CC-223, oral azacitidine in people with Carcinoma, Non-Small-Cell Lung and Non-Small Cell Lung Cancer, run by Celgene at 9 sites in 2 countries.
Trial summary
The main purpose of this first study combining an investigational dual mTOR inhibitor, CC-223, with other agents (erlotinib or the investigational agent, oral azacitidine) is to establish a maximum tolerated dose level for each combination in order to evaluate their effects in future clinical trials for advanced… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung, Non-Small Cell Lung Cancer
- What is being tested?
- CC-223, erlotinib and CC-223, oral azacitidine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- 9 sitesin 2 countries
- Study dates
- 1 May 2012to 11 Dec 2014
- 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
- Men and women, 18 years or older, with histologically or cytologically-confirmed, Stage IIIB/IV Non-Small Cell Lung Cancer with tumor progression following at least one prior treatment regimen (either chemotherapy or an Epidermal Growth Factor Receptor inhibitor) for advanced disease. There is no restriction on the number of prior treatment regimens allowed.
- Eastern Cooperative Oncology Group Performance Score of 0 to 1.
- Adequate organ function.
- Adequate contraception (if appropriate).
- Consent to retrieve archival tumor tissue.
- Consent to repeated tumor biopsy (dose expansion phase).
Who cannot join
- Prior systemic cancer-directed treatments or investigational drugs within 4 weeks or 5 half lives, whichever is shorter except erlotinib which may be continued with intervention in subjects allocated in Arm A.
- Symptomatic central nervous system metastases.
- Acute or chronic pancreatitis.
- Persistent diarrhea or malabsorption > Grade 2, despite medical management.
- Impaired cardiac function or significant cardiac disease.
- Diabetes on active treatment, fasting blood glucose > 126 mg/dL, HbA1c > 6.5%.
Show all 11Show fewer
- Known Human Immunodeficiency Virus, chronic hepatitis B or C infection.
- Prior treatment with an investigational dual TORC1/TORC2, PI3K, or Akt inhibitor. Prior treatment with rapalogs is allowed.
- Major surgery < 2 weeks prior to starting study drugs. No specific wash out is required for radiotherapy. Subjects must have recovered from any effects of recent therapy that might confound the safety evaluation of study drug.
- Pregnant or breastfeeding, inadequate contraception.
- History of concurrent second malignancies requiring ongoing systemic treatment.
Trial locations and contacts
9 sites in 2 countries.
9 sites in 2 countries
United States7 sites
Mary Crowley Cancer Research Centers - Medical City
Dallas, Texas, 75201
Cancer Center of the Carolinas
Greenville, South Carolina, 29605
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Cedars Sinai Medical Center, Inflammatory Bowel Disease Center
Los Angeles, California, 90048
Henry-Joyce Cancer Clinic
Nashville, Tennessee, 37232-5505
NYU School of Medicine
New York, New York, 10016
University of California, San Francisco
San Francisco, California, 9411
Spain2 sites
Vall d´Hebron University Hospital
Barcelona, 08035
Hospital Virgen del Rocio Servicio de Hematologia
Seville, 41013
About this study
Official title: A PHASE 1B, MULTI-CENTER, OPEN-LABEL STUDY OF THE MTOR KINASE INHIBITOR CC-223 IN COMBINATION WITH ERLOTINIB OR ORAL AZACITIDINE IN ADVANCED NON-SMALL CELL LUNG CANCER
The main purpose of this first study combining an investigational dual mTOR inhibitor, CC-223, with other agents (erlotinib or the investigational agent, oral azacitidine) is to establish a maximum tolerated dose level for each combination in order to evaluate their effects in future clinical trials for advanced non-small cell lung cancer.
- Being tested
- CC-223, erlotinib, CC-223, oral azacitidine
- Keywords
- Neoplasms, Pulmonary, Lung Cancer, Cancer of the Lung, Stage IIIB Non-Small Cell Lung Cancer, IV Non-Small Cell Lung Cancer, Non-Small Cell Lung Cancer
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Neoplasms, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CC-223, erlotinibDrug
Dose escalation: Combination doses start with 15 mg CC-223 and 100 mg erlotinib, or 15 mg CC-223 and 150 mg erlotonib, administered in 28-day cycles. Combination dose levels increase sequentially using predefined regimens until non-tolerated dose levels are established and a maximum tolerated dose combination has been identified for further study.
Dose expansion: The maximum tolerated doses are evaluated further for evidence of preliminary efficacy
CC-223, oral azacitidineDrug
Dose escalation: Combination doses start with 15 mg CC-223 and 200 mg oral azacitidine, administered in 28-day cycle. Combination dose levels increase sequentially using predefined regimens until non-tolerated dose levels are established and a maximum tolerated dose combination has been identified for further study.
Dose expansion: The maximum tolerated doses are evaluated further for evidence of preliminary efficacy
CC-223, oral azacitidineDrug
Dose escalation: Sequential dosing starts with 200 mg of oral azacitidine administered on Days 1 through 7 of each 28-day cycle, followed by daily dose level of 15 mg CC-223 on Days 8 through 28. Combination dose levels increase sequentially using predefined regimens until non-tolerated dose levels are established and a maximum tolerated dose combination has been identified for further study.
Dose expansion: The maximum tolerated doses are evaluated further for evidence of preliminary efficacy
| Study group | Role | What they receive |
|---|---|---|
| CC-223/erlotinib concurrent | Experimental | Cohorts will receive escalating continuous daily doses (15 mg and 30 mg) of CC-223 in capsules concurrently with at least two different daily dose levels of erlotinib tablets (100 mg and 150 mg) in 28-day cycles. Receives: Drug: CC-223, erlotinib |
| CC-223/oral azacitidine concurrent | Experimental | Cohorts will receive escalating continuous daily doses of CC-223 (15 mg and 30 mg) with one or more dose levels of oral azacitidine (200 mg or 300 mg, as two or three 100 mg tablets) administered on Day 1 to 21 of each 28-day cycle. Receives: Drug: CC-223, oral azacitidine |
| CC-223/oral azacitidine sequential | Experimental | Cohorts will receive escalating continuous daily dose levels of CC-223 (15 mg and 30 mg) administered on Days 8 through 28 sequentially with one or more dose levels of of oral azacitidine (200 mg or 300 mg, as two or three 100 mg tablets) administered on Days 1 to 7 of each 28-day cycle Receives: Drug: CC-223, oral azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events
Number of participants with adverse events
Measured: Up to 24 months
MTD
Maximum tolerated dose (MTD)
Measured: Up to 24 months
PK-Cmax
Pk-Maximum observed concentration in plasma (Cmax)
Measured: Up to 15 months
PK-AUC
Area under the plasma concentration-time curve (AUC)
Measured: Up to 15 months
PK-Tmax
PK-Time to maximum concentration (Tmax)
Measured: Up to 15 months
PK-T1/2
PK-Terminal half-life (T1/2)
Measured: Up to 15 months
PK-CL/F
PK-Apparent total body clearance (CL/F)
Measured: Up to 15 months
PK-Vz/F
PK-Apparent volume of distribution (Vz/F)
Measured: Up to 15 months
Secondary outcomes (4)
mTORC1 and mTORC2 pathway biomarkers
The effect of treatment on mTORC1 and mTORC2 pathway biomarkers in blood and tumor
Measured: Up to 15 months.
CC-223 metabolite, M1
CC-223 metabolite, M1, will be characterized
Measured: Up to 9 months
Tumor Response Rate
Tumor Response Rate using RECIST 1.1 (Eisenhauer, 2009)
Measured: Up to 24 months
Number of participants surviving without tumor progression
Number of participants surviving without tumor progression
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2012 (estimated)
- Study start1 May 2012
- Primary completion11 Dec 2014
- Study completion11 Dec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, Non-Small-Cell LungStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celgene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Kristen Hege, MD, Study director, Celgene Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01545947
- Sponsor's protocol ID
- CC-223-NSCL-001
- Other IDs
- 2011-005290-23
- Status last verified
- Nov 2019
- First submitted
- 2 Mar 2012
- Last updated
- 12 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A PHASE 1B, MULTI-CENTER, OPEN-LABEL STUDY OF THE MTOR KINASE INHIBITOR CC-223 IN COMBINATION WITH ERLOTINIB OR ORAL AZACITIDINE IN ADVANCED NON-SMALL CELL LUNG CANCER
- ClinicalTrials.gov ID
- NCT01545947
- Acronym / sponsor ID
- CC-223-NSCL-001
- Keywords
- Neoplasms, Pulmonary, Lung Cancer, Cancer of the Lung, Stage IIIB Non-Small Cell Lung Cancer, IV Non-Small Cell Lung Cancer, Non-Small Cell Lung Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- CelgeneIndustry (pharma, biotech, devices)
- Study start
- 1 May 2012 (actual)
- Primary completion
- 11 Dec 2014 (actual)
- Study completion
- 11 Dec 2014 (actual)
- First posted
- 7 Mar 2012 (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 main purpose of this first study combining an investigational dual mTOR inhibitor, CC-223, with other agents (erlotinib or the investigational agent, oral azacitidine) is to establish a maximum tolerated dose level for each combination in order to evaluate their effects in future clinical trials for advanced non-small cell lung cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| CC-223/erlotinib concurrent | Experimental | Drug: CC-223, erlotinibCohorts will receive escalating continuous daily doses (15 mg and 30 mg) of CC-223 in capsules concurrently with at least two different daily dose levels of erlotinib tablets (100 mg and 150 mg) in 28-day cycles. |
| CC-223/oral azacitidine concurrent | Experimental | Drug: CC-223, oral azacitidineCohorts will receive escalating continuous daily doses of CC-223 (15 mg and 30 mg) with one or more dose levels of oral azacitidine (200 mg or 300 mg, as two or three 100 mg tablets) administered on Day 1 to 21 of each 28-day cycle. |
| CC-223/oral azacitidine sequential | Experimental | Drug: CC-223, oral azacitidineCohorts will receive escalating continuous daily dose levels of CC-223 (15 mg and 30 mg) administered on Days 8 through 28 sequentially with one or more dose levels of of oral azacitidine (200 mg or 300 mg, as two or three 100 mg tablets) administered on Days 1 to 7 of each 28-day cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Men and women, 18 years or older, with histologically or cytologically-confirmed, Stage IIIB/IV Non-Small Cell Lung Cancer with tumor progression following at least one prior treatment regimen (either chemotherapy or an Epidermal Growth Factor Receptor inhibitor) for advanced disease. There is no restriction on the number of prior treatment regimens allowed.
- Eastern Cooperative Oncology Group Performance Score of 0 to 1.
- Adequate organ function.
- Adequate contraception (if appropriate).
- Consent to retrieve archival tumor tissue.
Key exclusion criteria (11 listed)
- Prior systemic cancer-directed treatments or investigational drugs within 4 weeks or 5 half lives, whichever is shorter except erlotinib which may be continued with intervention in subjects allocated in Arm A.
- Symptomatic central nervous system metastases.
- Acute or chronic pancreatitis.
- Persistent diarrhea or malabsorption > Grade 2, despite medical management.
- Impaired cardiac function or significant cardiac disease.
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-223, erlotinibDose escalation: Combination doses start with 15 mg CC-223 and 100 mg erlotinib, or 15 mg CC-223 and 150 mg erlotonib, administered in 28-day cycles. Combination dose levels increase sequentially using predefined regimens until non-tolerated dose levels are established and a maximum tolerated dose combination has been identified for further study. Dose expansion: The maximum tolerated doses are evaluated further for evidence of preliminary efficacy | Drug | CC-223/erlotinib concurrent |
| CC-223, oral azacitidineDose escalation: Combination doses start with 15 mg CC-223 and 200 mg oral azacitidine, administered in 28-day cycle. Combination dose levels increase sequentially using predefined regimens until non-tolerated dose levels are established and a maximum tolerated dose combination has been identified for further study. Dose expansion: The maximum tolerated doses are evaluated further for evidence of preliminary efficacy | Drug | CC-223/oral azacitidine concurrent |
| CC-223, oral azacitidineDose escalation: Sequential dosing starts with 200 mg of oral azacitidine administered on Days 1 through 7 of each 28-day cycle, followed by daily dose level of 15 mg CC-223 on Days 8 through 28. Combination dose levels increase sequentially using predefined regimens until non-tolerated dose levels are established and a maximum tolerated dose combination has been identified for further study. Dose expansion: The maximum tolerated doses are evaluated further for evidence of preliminary efficacy | Drug | CC-223/oral azacitidine sequential |
Primary outcome
Adverse events
Time frame: Up to 24 months
Number of participants with adverse events
MTD
Time frame: Up to 24 months
Maximum tolerated dose (MTD)
PK-Cmax
Time frame: Up to 15 months
Pk-Maximum observed concentration in plasma (Cmax)
PK-AUC
Time frame: Up to 15 months
Area under the plasma concentration-time curve (AUC)
PK-Tmax
Time frame: Up to 15 months
PK-Time to maximum concentration (Tmax)
PK-T1/2
Time frame: Up to 15 months
PK-Terminal half-life (T1/2)
PK-CL/F
Time frame: Up to 15 months
PK-Apparent total body clearance (CL/F)
PK-Vz/F
Time frame: Up to 15 months
PK-Apparent volume of distribution (Vz/F)
4 secondary outcomes
mTORC1 and mTORC2 pathway biomarkers
Time frame: Up to 15 months.
CC-223 metabolite, M1
Time frame: Up to 9 months
Tumor Response Rate
Time frame: Up to 24 months
Number of participants surviving without tumor progression
Time frame: Up to 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 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.
Kristen Hege, MD study director
Celgene Corporation
9 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-223, erlotinib and CC-223, oral azacitidine in people with Carcinoma, Non-Small-Cell Lung and Non-Small Cell Lung Cancer, run by Celgene at 9 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 6 inclusion and 11 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: finished, as of the sponsor's last update on 12 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 9 sites in United States, Spain. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Adverse events (time frame: Up to 24 months). The study lists 8 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 12 Nov 2019.