Back to resultsStudy Assessing Safety, Pharmacokinetics and Efficacy of CC-223 With Either Erlotinib or Oral Azacitidine in Advanced Non-Small Cell Lung Cancer
Primary Purpose
Carcinoma, Non-Small-Cell Lung, Non-Small Cell Lung Cancer
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
CC-223, erlotinib
CC-223, oral azacitidine
CC-223, oral azacitidine
Sponsored by
About this trial
This is an interventional treatment trial for Carcinoma, Non-Small-Cell Lung focused on measuring 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
Eligibility Criteria
Inclusion Criteria:
- 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).
Exclusion Criteria:
- 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%.
- 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.
Sites / Locations
- Cedars Sinai Medical Center, Inflammatory Bowel Disease Center
- University of California, San Francisco
- NYU School of Medicine
- Cancer Center of the Carolinas
- Henry-Joyce Cancer Clinic
- Mary Crowley Cancer Research Centers - Medical City
- The University of Texas MD Anderson Cancer Center
- Vall d´Hebron University Hospital
- Hospital Virgen del Rocio Servicio de Hematologia
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
CC-223/erlotinib concurrent
CC-223/oral azacitidine concurrent
CC-223/oral azacitidine sequential
Arm Description
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.
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.
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
Outcomes
Primary Outcome Measures
Adverse events
Number of participants with adverse events
MTD
Maximum tolerated dose (MTD)
PK-Cmax
Pk-Maximum observed concentration in plasma (Cmax)
PK-AUC
Area under the plasma concentration-time curve (AUC)
PK-Tmax
PK-Time to maximum concentration (Tmax)
PK-T1/2
PK-Terminal half-life (T1/2)
PK-CL/F
PK-Apparent total body clearance (CL/F)
PK-Vz/F
PK-Apparent volume of distribution (Vz/F)
Secondary Outcome Measures
mTORC1 and mTORC2 pathway biomarkers
The effect of treatment on mTORC1 and mTORC2 pathway biomarkers in blood and tumor
CC-223 metabolite, M1
CC-223 metabolite, M1, will be characterized
Tumor Response Rate
Tumor Response Rate using RECIST 1.1 (Eisenhauer, 2009)
Number of participants surviving without tumor progression
Number of participants surviving without tumor progression
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01545947
Brief Title
Study Assessing Safety, Pharmacokinetics and Efficacy of CC-223 With Either Erlotinib or Oral Azacitidine in Advanced Non-Small Cell Lung Cancer
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
May 1, 2012 (Actual)
Primary Completion Date
December 11, 2014 (Actual)
Study Completion Date
December 11, 2014 (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 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Non-Small-Cell Lung, Non-Small Cell Lung Cancer
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
76 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CC-223/erlotinib concurrent
Arm Type
Experimental
Arm Description
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.
Arm Title
CC-223/oral azacitidine concurrent
Arm Type
Experimental
Arm Description
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.
Arm Title
CC-223/oral azacitidine sequential
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
CC-223, erlotinib
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
CC-223, oral azacitidine
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
CC-223, oral azacitidine
Intervention Description
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
Primary Outcome Measure Information:
Title
Adverse events
Description
Number of participants with adverse events
Time Frame
Up to 24 months
Title
MTD
Description
Maximum tolerated dose (MTD)
Time Frame
Up to 24 months
Title
PK-Cmax
Description
Pk-Maximum observed concentration in plasma (Cmax)
Time Frame
Up to 15 months
Title
PK-AUC
Description
Area under the plasma concentration-time curve (AUC)
Time Frame
Up to 15 months
Title
PK-Tmax
Description
PK-Time to maximum concentration (Tmax)
Time Frame
Up to 15 months
Title
PK-T1/2
Description
PK-Terminal half-life (T1/2)
Time Frame
Up to 15 months
Title
PK-CL/F
Description
PK-Apparent total body clearance (CL/F)
Time Frame
Up to 15 months
Title
PK-Vz/F
Description
PK-Apparent volume of distribution (Vz/F)
Time Frame
Up to 15 months
Secondary Outcome Measure Information:
Title
mTORC1 and mTORC2 pathway biomarkers
Description
The effect of treatment on mTORC1 and mTORC2 pathway biomarkers in blood and tumor
Time Frame
Up to 15 months.
Title
CC-223 metabolite, M1
Description
CC-223 metabolite, M1, will be characterized
Time Frame
Up to 9 months
Title
Tumor Response Rate
Description
Tumor Response Rate using RECIST 1.1 (Eisenhauer, 2009)
Time Frame
Up to 24 months
Title
Number of participants surviving without tumor progression
Description
Number of participants surviving without tumor progression
Time Frame
Up to 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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).
Exclusion Criteria:
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%.
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kristen Hege, MD
Organizational Affiliation
Celgene Corporation
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
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
9411
Country
United States
Facility Name
NYU School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Cancer Center of the Carolinas
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
Henry-Joyce Cancer Clinic
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-5505
Country
United States
Facility Name
Mary Crowley Cancer Research Centers - Medical City
City
Dallas
State/Province
Texas
ZIP/Postal Code
75201
Country
United States
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Vall d´Hebron University Hospital
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Virgen del Rocio Servicio de Hematologia
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
12. IPD Sharing Statement
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Study Assessing Safety, Pharmacokinetics and Efficacy of CC-223 With Either Erlotinib or Oral Azacitidine in Advanced Non-Small Cell Lung Cancer
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