Study Assessing Safety, Pharmacokinetics and Efficacy of CC-223 With Either Erlotinib or Oral Azacitidine in Advanced Non-Small Cell Lung Cancer

Non-Small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01545947
• Other study ID #: CC-223-NSCL-001
• Secondary ID: 2011-005290-23
• Status: Completed
• Phase: Phase 1
• Start date: May 1, 2012
• Est. completion date: December 11, 2014

Study information

• Verified date: November 2019
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 non-small cell lung cancer.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: December 11, 2014
• Est. primary completion date: December 11, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 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.

2. Eastern Cooperative Oncology Group Performance Score of 0 to 1.

3. Adequate organ function.

4. Adequate contraception (if appropriate).

5. Consent to retrieve archival tumor tissue.

6. Consent to repeated tumor biopsy (dose expansion phase).

Exclusion Criteria:

1. 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.

2. Symptomatic central nervous system metastases.

3. Acute or chronic pancreatitis.

4. Persistent diarrhea or malabsorption > Grade 2, despite medical management.

5. Impaired cardiac function or significant cardiac disease.

6. Diabetes on active treatment, fasting blood glucose > 126 mg/dL, HbA1c > 6.5%.

7. Known Human Immunodeficiency Virus, chronic hepatitis B or C infection.

8. Prior treatment with an investigational dual TORC1/TORC2, PI3K, or Akt inhibitor. Prior treatment with rapalogs is allowed.

9. 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.

10. Pregnant or breastfeeding, inadequate contraception.

11. History of concurrent second malignancies requiring ongoing systemic treatment.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

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
• 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
• 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

Locations

Country	Name	City	State
Spain	Vall d´Hebron University Hospital	Barcelona
Spain	Hospital Virgen del Rocio Servicio de Hematologia	Sevilla
United States	Mary Crowley Cancer Research Centers - Medical City	Dallas	Texas
United States	Cancer Center of the Carolinas	Greenville	South Carolina
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Cedars Sinai Medical Center, Inflammatory Bowel Disease Center	Los Angeles	California
United States	Henry-Joyce Cancer Clinic	Nashville	Tennessee
United States	NYU School of Medicine	New York	New York
United States	University of California, San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events	Number of participants with adverse events	Up to 24 months
Primary	MTD	Maximum tolerated dose (MTD)	Up to 24 months
Primary	PK-Cmax	Pk-Maximum observed concentration in plasma (Cmax)	Up to 15 months
Primary	PK-AUC	Area under the plasma concentration-time curve (AUC)	Up to 15 months
Primary	PK-Tmax	PK-Time to maximum concentration (Tmax)	Up to 15 months
Primary	PK-T1/2	PK-Terminal half-life (T1/2)	Up to 15 months
Primary	PK-CL/F	PK-Apparent total body clearance (CL/F)	Up to 15 months
Primary	PK-Vz/F	PK-Apparent volume of distribution (Vz/F)	Up to 15 months
Secondary	mTORC1 and mTORC2 pathway biomarkers	The effect of treatment on mTORC1 and mTORC2 pathway biomarkers in blood and tumor	Up to 15 months.
Secondary	CC-223 metabolite, M1	CC-223 metabolite, M1, will be characterized	Up to 9 months
Secondary	Tumor Response Rate	Tumor Response Rate using RECIST 1.1 (Eisenhauer, 2009)	Up to 24 months
Secondary	Number of participants surviving without tumor progression	Number of participants surviving without tumor progression	Up to 24 months