A Study of Cixutumumab (IMC-A12) in Islet Cell Cancer
Condition: Carcinoma; Neuroendocrine Tumors
MeSH terms: Carcinoma; Neuroendocrine Tumors
Intervention: Cixutumumab; depot octreotide
Intervention description: Participants will receive cixutumumab IV 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.; Participants must be receiving depot octreotide at the time of enrolling into the study. Participants on stable doses of depot octreotide will continue to receive the same dose and schedule of their last regimen.
Intervention MeSH terms: Octreotide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 43.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Islet Cell; CARCINOMA, ISLET CELL; Octreotide; depot octreotide acetate; Insulin-Like Growth Factor (IGF) 1; Metastatic, Carcinoid or Islet Cell; Neuroendocrine Tumors

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