Cixutumumab, Everolimus, and Octreotide Acetate in Treating Patients With Advanced Low to Intermediate Grade Neuroendocrine Carcinoma
Gastrin-Producing Neuroendocrine Tumor
Lung Carcinoid Tumor
Metastatic Digestive System Neuroendocrine Tumor G1
Pancreatic Polypeptide Tumor
Recurrent Digestive System Neuroendocrine Tumor G1
Recurrent Merkel Cell Carcinoma
Recurrent Pancreatic Neuroendocrine Carcinoma
Regional Digestive System Neuroendocrine Tumor G1
Somatostatin-Producing Neuroendocrine Tumor
Stage III Merkel Cell Carcinoma
Stage IV Merkel Cell Carcinoma
Thyroid Gland Medullary Carcinoma
Other: Laboratory Biomarker Analysis
Drug: Octreotide Acetate
Other: Pharmacological Study
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of Anti-IGF-1R Monoclonal Antibody, IMC-A12, and mTOR Inhibitor, Everolimus, in Advanced Low to Intermediate Grade Neuroendocrine Carcinoma|
- Incidence of dose-limiting toxicities (DLTs) for the combination of cixutumumab and everolimus with octreotide acetate [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]Analysis will be performed using a patient summary of the number of cycles of study drug administered by initial dose level, and will be presented including a flag for DLTs which occurred during course 1. The recommended Phase II dose will also be presented.
- Pharmacodynamic markers in blood and tumor tissue [ Time Frame: Up to day 1 of course 4 ] [ Designated as safety issue: No ]Descriptive statistics for the changes from baseline in blood and tissue biomarkers will be presented by response category in an attempt to characterize these changes with respect to efficacy.
- Pharmacokinetic parameters [ Time Frame: Pre-dose and day 1 of courses 1-7 ] [ Designated as safety issue: No ]Descriptive statistics will be used for plasma drug concentration data. Calculated parameters will include maximum concentration and minimum concentration.
- Safety profile of cixutumumab and everolimus with octreotide acetate among patients with advanced neuroendocrine tumors, defined by the incidence of adverse events [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]Safety data will be tabulated for all patients who receive any amount of study medication. These data will include adverse events and laboratory parameters. Adverse events will be tabulated by body system, preferred term, severity and relation to treatment. The tabulation of adverse events will be done using the CTCAE version 4.0.
- Anti-tumor activity as determined by RECIST [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: No ]
- Changes in drug-induced molecular markers [ Time Frame: Baseline to up to day 1 of course 4 ] [ Designated as safety issue: No ]
- Changes in molecular markers [ Time Frame: Baseline to up to day 1 of course 4 ] [ Designated as safety issue: No ]
|Study Start Date:||October 2010|
|Primary Completion Date:||May 2013 (Final data collection date for primary outcome measure)|
Experimental: Treatment (cixutumumab, octreotide acetate, everolimus)
Patients receive cixutumumab IV over 60-90 minutes and octreotide acetate IM on day 1 and everolimus PO QD on days 1-21. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.
Other Names:Drug: Everolimus
Other Names:Other: Laboratory Biomarker Analysis
Correlative studiesDrug: Octreotide Acetate
Other Names:Other: Pharmacological Study
I. To recommend a phase 2 dose for the combination of IMC-A12 (cixutumumab) and everolimus, given with octreotide long-acting release (LAR) (octreotide acetate), in patients with advanced neuroendocrine tumors.
II. To describe the pharmacokinetics of IMC-A12 given once every 21 days in combination with everolimus and octreotide LAR.
III. To evaluate pharmacodynamic markers in blood, and tumor tissue.
I. To evaluate the safety profile of IMC-A12 and everolimus with octreotide LAR.
II. To explore the anti-tumor activity of the combination of IMC-A12 and everolimus as defined by Response Evaluation Criteria in Solid Tumors (RECIST) response rate and progression-free survival (PFS).
I. To explore baseline molecular marker and drug-induced molecular marker changes that may predict clinical outcome.
OUTLINE: This is a dose-escalation study of cixutumumab.
Patients receive cixutumumab intravenously (IV) over 60-90 minutes and octreotide acetate intramuscularly (IM) on day 1 and everolimus orally (PO) once daily (QD) on days 1-21. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01204476
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||James Yao||M.D. Anderson Cancer Center|