Study Assessing Safety, Pharmacokinetics and Efficacy of CC-223 With Either Erlotinib or Oral Azacitidine in Advanced Non-Small Cell Lung Cancer
This study is ongoing, but not recruiting participants.
Sponsor:
Celgene Corporation
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01545947
First received: March 2, 2012
Last updated: November 24, 2014
Last verified: November 2014
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Carcinoma, Non-Small-Cell Lung Non-Small Cell Lung Cancer |
Drug: CC-223, erlotinib Drug: CC-223, oral azacitidine |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| 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 |
Resource links provided by NLM:
Further study details as provided by Celgene Corporation:
Primary Outcome Measures:
- Adverse events [ Time Frame: Up to 24 months ] [ Designated as safety issue: Yes ]Number of participants with adverse events
- MTD [ Time Frame: Up to 24 months ] [ Designated as safety issue: Yes ]Maximum tolerated dose (MTD)
- PK-Cmax [ Time Frame: Up to 15 months ] [ Designated as safety issue: No ]Pk-Maximum observed concentration in plasma (Cmax)
- PK-AUC [ Time Frame: Up to 15 months ] [ Designated as safety issue: No ]Area under the plasma concentration-time curve (AUC)
- PK-Tmax [ Time Frame: Up to 15 months ] [ Designated as safety issue: No ]PK-Time to maximum concentration (Tmax)
- PK-T1/2 [ Time Frame: Up to 15 months ] [ Designated as safety issue: No ]PK-Terminal half-life (T1/2)
- PK-CL/F [ Time Frame: Up to 15 months ] [ Designated as safety issue: No ]PK-Apparent total body clearance (CL/F)
- PK-Vz/F [ Time Frame: Up to 15 months ] [ Designated as safety issue: No ]PK-Apparent volume of distribution (Vz/F)
Secondary Outcome Measures:
- mTORC1 and mTORC2 pathway biomarkers [ Time Frame: Up to 15 months. ] [ Designated as safety issue: No ]The effect of treatment on mTORC1 and mTORC2 pathway biomarkers in blood and tumor
- CC-223 metabolite, M1 [ Time Frame: Up to 9 months ] [ Designated as safety issue: No ]CC-223 metabolite, M1, will be characterized
- Tumor Response Rate [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]Tumor Response Rate using RECIST 1.1 (Eisenhauer, 2009)
- Number of participants surviving without tumor progression [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]Number of participants surviving without tumor progression
| Estimated Enrollment: | 108 |
| Study Start Date: | April 2012 |
| Estimated Study Completion Date: | December 2015 |
| Estimated Primary Completion Date: | March 2015 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: CC-223/erlotinib concurrent
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.
|
Drug: CC-223, erlotinib
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 |
|
Experimental: CC-223/oral azacitidine concurrent
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.
|
Drug: CC-223, oral azacitidine
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 |
|
Experimental: CC-223/oral azacitidine sequential
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
|
Drug: CC-223, oral azacitidine
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 |
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01545947
Please refer to this study by its ClinicalTrials.gov identifier: NCT01545947
Locations
| United States, California | |
| Cedars Sinai | |
| Los Angeles, California, United States, 90048 | |
| University of California San Francisco | |
| San Francisco, California, United States, 94115 | |
| United States, New York | |
| NYU Cancer Institute | |
| New York, New York, United States, 10016 | |
| United States, South Carolina | |
| ITOR Cancer Center of North Carolina | |
| Greenville, South Carolina, United States, 29605 | |
| United States, Tennessee | |
| Vanderbilt University Medical Center | |
| Nashville, Tennessee, United States, 37232 | |
| United States, Texas | |
| Mary Crowley Cancer Research Center | |
| Dallas, Texas, United States, 75201 | |
| University of Texas MD Anderson | |
| Houston, Texas, United States, 77030 | |
| Spain | |
| Hospital Universitari Vall d'Hebron | |
| Barcelona, Spain, 08035 | |
| Hospital Universitario Virgen del Rocío | |
| Sevilla, Spain, 41013 | |
| Hospital Universitario Clínico de Valencia | |
| Valencia, Spain, 46010 | |
Sponsors and Collaborators
Celgene Corporation
Investigators
| Study Director: | Kristen Hege, MD | Celgene Corporation |
More Information
No publications provided
| Responsible Party: | Celgene Corporation |
| ClinicalTrials.gov Identifier: | NCT01545947 History of Changes |
| Other Study ID Numbers: | CC-223-NSCL-001, 2011-005290-23 |
| Study First Received: | March 2, 2012 |
| Last Updated: | November 24, 2014 |
| Health Authority: | United States: Food and Drug Administration United States: Institutional Review Board France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Spain: Agencia Española de Medicamentos y Productos Sanitarios |
Keywords provided by Celgene Corporation:
|
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 |
Additional relevant MeSH terms:
|
Carcinoma, Non-Small-Cell Lung Lung Neoplasms Bronchial Neoplasms Carcinoma, Bronchogenic Lung Diseases Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms |
Azacitidine Erlotinib Antimetabolites Antimetabolites, Antineoplastic Antineoplastic Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Protein Kinase Inhibitors Therapeutic Uses |
ClinicalTrials.gov processed this record on March 03, 2015