Clinical trial NCT00781911: A Study of Cixutumumab (IMC-A12) in Islet Cell Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma
Neuroendocrine Tumors
Keywords: Islet Cell
CARCINOMA, ISLET CELL
Octreotide
depot octreotide acetate
Insulin-Like Growth Factor (IGF) 1
Metastatic, Carcinoid or Islet Cell
Neuroendocrine Tumors
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2008-10-29
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Determine the 6-month progression free survival (PFS) rate associated with cixutumumab in combination with depot octreotide acetate (octreotide) in participants with metastatic neuroendocrine tumors.


Eligibility criteria: Inclusion Criteria:

* The participant has well-differentiated or moderately-differentiated, histologically confirmed neuroendocrine carcinoma, including carcinoid of any location and islet cell tumors
* The participant has metastatic disease at the time of study entry
* The participant 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, adrenocorticotropin hormone (ACTH), gastrin, or other tumor specific biochemical markers), or both
* The participant is age ≥ 18 years
* The participant's tumor has Ki-67 expression ≤ 20%
* The participant is receiving depot octreotide therapy at the time of enrolling into the study
* The participant 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 participant is no longer a candidate for surgery, embolization, or radiofrequency ablation therapy
* The participant has experienced radiographic, biochemical, and/or scintigraphic disease progression while on a regimen that includes octreotide
* The participant 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. Participants that have received palliative radiation therapy to bony metastases prior to the first dose of study medication are eligible
* The participant has a life expectancy of \> 3 months
* The participant has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2
* The participant has adequate hematologic function as defined by absolute neutrophil count ≥ 1500/microliters (μL), hemoglobin ≥ 9 gram/deciliter (g/dL), and platelet count ≥100,000/μL
* The participant 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 participant 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 participant has adequate renal function as defined by serum creatinine ≤ 1.5 x the institutional ULN or creatinine clearance ≥ 60 milliliter/minute (mL/min) for participants with creatinine levels above the ULN
* The participant has fasting serum glucose \< 160 milligram/deciliter (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 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 participant has the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* The participant has uncontrolled brain or leptomeningeal metastases
* The participant 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 participant is receiving any other investigational agent(s)
* The participant has received therapeutic radiolabeled somatostatin analogues
* The participant has received more than 2 prior regimens of systemic therapy in the metastatic setting
* The participant has a history of treatment with other agents targeting the IGF receptor
* The participant has a history of allergic reactions attributed to compounds of chemical or biologic composition similar to that of cixutumumab or to octreotide
* The participant has poorly controlled diabetes mellitus. Participants 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 participant 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 participant is pregnant or lactating
* The participant is known to be positive for infection with the human immunodeficiency virus
* The participant 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

Primary outcomes:
measure: Percentage of Participants With Progression-Free Survival (PFS) Rate at Six Months
timeFrame: From Start of Study Treatment to Progressive Disease or Death Due to Any Cause (Up to 6 Months)
Secondary outcomes:
measure: Percentage of Participants Who Achieve Modified Objective Response Rate (ORR) of Complete Response (CR), Partial Response (PR) and Minor Response (MR) Modified Objective Response Rate (mORR)
timeFrame: From Start of Treatment Baseline to Disease Progression (Up to 18 Months)
measure: Percentage of Participants With a Biochemical Response Rate
timeFrame: From Start of Treatment Up to 18 Months
measure: Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)
timeFrame: 18 months
measure: Pharmacokinetics (PK): Maximum Concentration (Cmax) Cycle 1
timeFrame: Prior to the final infusion, immediately after the infusion, and 1, 2, 4, 8, 48, 96, 168, and 336 hours after the completion of the final infusion
measure: PK: Half-life (t 1/2) Cycle 1
timeFrame: Prior to the final infusion, immediately after the infusion, and 1, 2, 4, 8, 48, 96, 168, and 336 hours after the completion of the final infusion
measure: PK: Area Under Concentration (AUCinf) Cycle 1
timeFrame: Prior to the final infusion, immediately after the infusion, and 1, 2, 4, 8, 48, 96, 168, and 336 hours after the completion of the final infusion
measure: PK: Clearance (CL) Cycle 1
timeFrame: Prior to the final infusion, immediately after the infusion, and 1, 2, 4, 8, 48, 96, 168, and 336 hours after the completion of the final infusion
measure: PK: Volume at Steady State (Vss) Cycle 1
timeFrame: Prior to the final infusion, immediately after the infusion, and 1, 2, 4, 8, 48, 96, 168, and 336 hours after the completion of the final infusion
measure: Serum Anti-Cixutumumab Antibody Assessment
timeFrame: 18 months
measure: Pharmacodynamics Markers; Concentration of Insulin-like Growth Factor I, II (IGF-I, IGF-II), IGF Body Fat (IGFBF)-1 and IGFBF-2
timeFrame: 18 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: ImClone Investigational Site
state: California
city: Los Angeles
country: United States
facility: ImClone Investigational Site
state: California
city: Aurora
country: United States
facility: ImClone Investigational Site
state: Colorado
city: Atlanta
country: United States
facility: ImClone Investigational Site
state: Georgia
city: Indianapolis
country: United States
facility: ImClone Investigational Site
state: Indiana
city: Kenner
country: United States
facility: ImClone Investigational Site
state: Louisiana
city: Columbus
country: United States
facility: ImClone Investigational Site
state: Ohio
city: Providence
country: United States
facility: ImClone Investigational Site
state: Rhode Island
city: Nashville
country: United States
facility: ImClone Investigational Site
state: Tennessee
city: Dallas
country: United States
facility: ImClone Investigational Site
state: Texas
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: