Cixutumumab, Everolimus, and Octreotide Acetate in Treating Patients With Advanced Low to Intermediate Grade Neuroendocrine Carcinoma
|ClinicalTrials.gov Identifier: NCT01204476|
Recruitment Status : Completed
First Posted : September 17, 2010
Last Update Posted : July 15, 2016
|Condition or disease||Intervention/treatment||Phase|
|Gastrin-Producing Neuroendocrine Tumor Lung Carcinoid Tumor Metastatic Digestive System Neuroendocrine Tumor G1 Pancreatic Glucagonoma Pancreatic Insulinoma Pancreatic Polypeptide Tumor Paraganglioma 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||Biological: Cixutumumab Drug: Everolimus Other: Laboratory Biomarker Analysis Drug: Octreotide Acetate Other: Pharmacological Study||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||27 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||October 2010|
|Actual Primary Completion Date :||July 2014|
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: Laboratory Biomarker Analysis
Drug: Octreotide Acetate
Other: Pharmacological Study
- Incidence of dose-limiting toxicities (DLTs) for the combination of cixutumumab and everolimus with octreotide acetate [ Time Frame: 21 days ]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 ]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 ]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 ]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 ]
- Changes in drug-induced molecular markers [ Time Frame: Baseline to up to day 1 of course 4 ]
- Changes in molecular markers [ Time Frame: Baseline to up to day 1 of course 4 ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01204476
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||James Yao||M.D. Anderson Cancer Center|