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
  Purpose

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.


Condition Intervention Phase
Carcinoma
Neuroendocrine Tumors
Biological: IMC-A12 (cixutumumab)
Drug: depot octreotide
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: Approximately 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 43
Study Start Date: February 2009
Estimated Study Completion Date: December 2014
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Carcinoid tumor 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: Islet cell carcinoma 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00781911

Locations
United States, California
ImClone Investigational Site
Los Angeles, California, United States, 90095
ImClone Investigational Site
Los Angeles, California, United States, 90033
United States, Colorado
ImClone Investigational Site
Aurora, Colorado, United States, 80045
United States, Georgia
ImClone Investigational Site
Atlanta, Georgia, United States, 30318
United States, Indiana
ImClone Investigational Site
Indianapolis, Indiana, United States, 46202
United States, Louisiana
ImClone Investigational Site
Kenner, Louisiana, United States, 70065
United States, Ohio
ImClone Investigational Site
Columbus, Ohio, United States, 43210
United States, Rhode Island
ImClone Investigational Site
Providence, Rhode Island, United States, 02903
United States, Tennessee
ImClone Investigational Site
Nashville, Tennessee, United States, 37232
United States, Texas
ImClone Investigational Site
Dallas, Texas, United States, 75246
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00781911     History of Changes
Other Study ID Numbers: 13929, CP13-0710, I5A-IE-JAEE
Study First Received: October 27, 2008
Last Updated: July 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:
Islet Cell
CARCINOMA, ISLET CELL
Octreotide
depot octreotide acetate
Insulin-Like Growth Factor (IGF) 1
Metastatic, Carcinoid or Islet Cell
Neuroendocrine Tumors

Additional relevant MeSH terms:
Carcinoma
Neuroendocrine Tumors
Carcinoma, Islet Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Adenocarcinoma
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Octreotide
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 28, 2014