Clinical Trial: Cixutumumab, Everolimus, and Octreotide Acetate in Treating Patients With Advanced Low to Intermediate Grade Neuroendocrine Carcinoma

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief Summary: This phase I trial studies the side effects and best dose of cixutumumab when given together with everolimus and octreotide acetate in treating patients with advanced low- or intermediate-grade neuroendocrine cancer. Monoclonal antibodies, such as cixutumumab, may find tumor cells and help carry tumor-killing substances to them. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Octreotide acetate may interfere with the growth of tumor cells and slow the growth of neuroendocrine cancer. Giving cixutumumab together with everolimus and octreotide acetate may be a better treatment for neuroendocrine cancer.

Detailed Summary:

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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).

TERTIARY OBJECTIVES:

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.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • 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.


Original Primary Outcome:

  • Dose-limiting toxicities
  • Safety profile
  • Pharmacodynamic markers
  • Antitumor activity as assessed by RECIST criteria


Current Secondary Outcome: Anti-tumor activity as determined by RECIST [ Time Frame: Up to 30 days after completion of study treatment ]

Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: September 16, 2010
Date Started: October 2010
Date Completion:
Last Updated: July 14, 2016
Last Verified: July 2016