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A Study of IMC-A12 in Islet Cell Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00781911
First received: October 27, 2008
Last updated: July 3, 2014
Last verified: July 2014

October 27, 2008
July 3, 2014
February 2009
July 2011   (final data collection date for primary outcome measure)
Progression-free survival (PFS) [ Time Frame: Approximately 6 months ] [ Designated as safety issue: No ]
To determine the 6-month progression-free survival (PFS) rate associated with IMC-A12 in combination with depot octreotide acetate (octreotide) in patients with metastatic neuroendocrine tumors. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00781911 on ClinicalTrials.gov Archive Site
  • Objective response rate (ORR) [ Time Frame: Approximately 18 months ] [ Designated as safety issue: No ]
  • Biochemical response rate [ Time Frame: Approximately 18 months ] [ Designated as safety issue: No ]
    Determine the biochemical response rate (≥ 50% reduction in tumor-specific markers; may include, not limited to 24 hour urine 5-hydroxyindoleacetic acid , chromogranin A, ACTH, or gastrin) in the subset of patients with biochemically measurable disease.
  • Summary Listing of Participants Reporting Treatment-Emergent Adverse Events (AEs) [ Time Frame: Approximately 18 months ] [ Designated as safety issue: Yes ]
  • Maximum concentration (Cmax) prior to day 1 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Maximum concentration (Cmax) is the maximum peak concentration measured in blood plasma prior to receiving study drug.
  • Half-life (t 1/2) prior to day 1 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Half-life (t 1/2) is the maximum peak concentration measured in blood plasma prior to receiving study drug.
  • Area under concentration (AUCinf) prior to day 1 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Area under concentration (AUCinf) is the area under serum concentration versus time curve from time zero extrapolated to infinity prior to receiving study drug.
  • Clearance (CL) prior to day 1 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Volume at steady state (Vss) prior to day 1 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Serum Anti-IMC-A12 Antibody Assessment [ Time Frame: Approximately 18 months ] [ Designated as safety issue: Yes ]
  • Effect of IMC-A12 in combination with depot octreotide on selected pharmacodynamic markers; concentration of IGF-I, IGF-II, IGFBF-1 and IGFBF-2 [ Time Frame: Approximately 18 months ] [ Designated as safety issue: No ]
  • To determine the modified objective response rate (ORR) in patients with radiographically measurable disease [ Time Frame: 18 months or until patients progress ] [ Designated as safety issue: No ]
  • Determine the biochemical response rate (≥ 50% reduction in tumor-specific markers; may include, not limited to 24 hour urine 5-hydroxyindoleacetic acid , chromogranin A, ACTH, or gastrin) in the subset of patients with biochemically measurable disease. [ Time Frame: 18 months or until patients progress ] [ Designated as safety issue: No ]
  • To evaluate the safety, tolerability, and adverse event profile of IMC-A12 in combination with depot octreotide [ Time Frame: 18 months or until patients progress ] [ Designated as safety issue: Yes ]
  • To evaluate the pharmacokinetic profile of IMC-A12 [ Time Frame: 18 months or until patients progress ] [ Designated as safety issue: No ]
  • To screen for the development of antibodies against IMC-A12 [ Time Frame: 18 months or until patients progress ] [ Designated as safety issue: Yes ]
  • To evaluate the effect of IMC-A12 in combination with depot octreotide on selected pharmacodynamic markers [ Time Frame: 18 months or until patients progress ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Study of IMC-A12 in Islet Cell Cancer
A Phase 2, Multicenter, Two Tier Study of IMC-A12 in Combination With Depot Octreotide in Patients With Metastatic, Well or Moderately Differentiated Carcinoid or Islet Cell Carcinoma

Determine the 6-month progression free survival (PFS) rate associated with IMC-A12 in combination with depot octreotide acetate (octreotide) in patients with metastatic neuroendocrine tumors.

Not Provided
Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Carcinoma
  • Neuroendocrine Tumors
  • Biological: IMC-A12 (cixutumumab)
    Patients will receive intravenous (I.V.) IMC-A12 (cixutumumab) 10 mg/kg over 1 hour every 2 weeks. ). Treatment will continue until there is evidence of disease progression, intolerable toxicity, or other withdrawal criteria are met.
    Other Name: cixutumumab
  • Drug: depot octreotide
    Patients must be receiving depot octreotide at the time of enrolling into the study.Patients on stable doses of depot octreotide will continue to receive the same dose and schedule of their last regimen.
  • Experimental: Carcinoid tumor
    Interventions:
    • Biological: IMC-A12 (cixutumumab)
    • Drug: depot octreotide
  • Experimental: Islet cell carcinoma
    Interventions:
    • Biological: IMC-A12 (cixutumumab)
    • Drug: depot octreotide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
43
December 2014
July 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • The patient has well-differentiated or moderately-differentiated, histologically confirmed neuroendocrine carcinoma, including carcinoid of any location and islet cell tumors
  • The patient has metastatic disease at the time of study entry
  • The patient must have a tumor measurable according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, measurable by elevated tumor markers (eg, 24-hour urine 5-HIAA, chromogranin A, ACTH, gastrin, or other tumor specific biochemical markers), or both
  • The patient is age ≥ 18 years
  • The patient's tumor has Ki-67 expression ≤ 20%
  • The patient is receiving depot octreotide therapy at the time of enrolling into the study
  • The patient has received 0 - 2 systemic anticancer regimens in addition to depot octreotide, which may have included chemotherapy, interferon, antiangiogenic therapy, other targeted treatments, or a combination of such treatments
  • The patient is no longer a candidate for surgery, embolization, or radiofrequency ablation therapy
  • The patient has experienced radiographic, biochemical, and/or scintigraphic disease progression while on a regimen that includes octreotide
  • The patient has completed prior chemotherapy and/or radiotherapy with curative intent at least 3 weeks prior to the administration of the first dose of study therapy. Patients that have received palliative radiation therapy to bony metastases prior to the first dose of study medication are eligible
  • The patient has a life expectancy of > 3 months
  • The patient has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2
  • The patient has adequate hematologic function as defined by absolute neutrophil count ≥ 1500/μL, hemoglobin ≥ 9 g/dL, and platelet count ≥100,000/μL
  • The patient has adequate hepatic function as defined by a total bilirubin ≤ 1.5 x the upper limit of normal (ULN), and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x the ULN (or ≤ 5 x the ULN in the presence of known liver metastases)
  • The patient either has adequate coagulation function as defined by international normalized ratio (INR) ≤ 1.5 and partial thromboplastin time (PTT) no more than 5 seconds above the ULN, or is on a stable dose of anticoagulant
  • The patient has adequate renal function as defined by serum creatinine ≤ 1.5 x the institutional ULN or creatinine clearance ≥ 60 mL/min for patients with creatinine levels above the ULN
  • The patient has fasting serum glucose < 160 mg/dL and hemoglobin A1c (HgbA1c)≤ 7. If baseline nonfasting glucose is < 160 mg/dL, fasting glucose measurement is not required
  • Because the teratogenicity of IMC-A12 (cixutumumab) is not known, women of childbearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
  • The patient has the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • The patient has uncontrolled brain or leptomeningeal metastases
  • The patient has not recovered to Grade ≤ 1 from adverse events due to agents administered more than 4 weeks prior to study entry (except for alopecia)
  • The patient is receiving any other investigational agent(s)
  • The patient has received therapeutic radiolabeled somatostatin analogues
  • The patient has received more than 2 prior regimens of systemic therapy in the metastatic setting
  • The patient has a history of treatment with other agents targeting the IGF receptor
  • The patient has a history of allergic reactions attributed to compounds of chemical or biologic composition similar to that of IMC-A12 (cixutumumab) or to octreotide
  • The patient has poorly controlled diabetes mellitus. Patients with a history of diabetes mellitus are allowed to participate, provided that their fasting glucose < 160 mg/dL or below the ULN and that they are on a stable dietary or therapeutic regimen for this condition
  • The patient has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics, symptomatic congestive heart failure, uncontrolled hypertension, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • The patient is pregnant or lactating
  • The patient is known to be positive for infection with the human immunodeficiency virus
  • The patient has a history of another primary cancer, with the exception of: a) curatively resected nonmelanomatous skin cancer; b) curatively treated cervical carcinoma in-situ; or c) other primary solid tumor curatively resected or treated with no known active disease present and no treatment administered for the last 3 years
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00781911
13929, CP13-0710, I5A-IE-JAEE
Yes
Eli Lilly and Company
Eli Lilly and Company
Not Provided
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
Eli Lilly and Company
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP