Clinical and Translational Study of MK-0646 in Patients With Metastatic Neuroendocrine Tumors (NET)
Condition: Neuroendocrine Tumors; Metastatic Neuroendocrine Tumors
MeSH terms: Neoplasms; Neuroendocrine Tumors
Intervention: MK-0646
Intervention description: MK-0646 (20 mg/mL) in sterilized solution for IV infusion (12.7 mL to deliver 12.0 mL) will be used for a dose of 10 mg/kg IV weekly administered over 60 minutes.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: MK-0646

Summary:

      The purpose of this study is to test a new drug for neuroendocrine tumors. We think that this
      new drug may help control your tumor.

      MK-0646 is a monoclonal antibody. An antibody is a protein that is able to attach to specific
      target on cancer cells. This target helps the cancer cells grow and divide. By attaching to
      the target, it may stop the cancer cells from further growth and dividing. This study will
      help find out if MK-0646 is a helpful drug when taken in patients with neuroendocrine tumor.

      This study is a phase 2 study. The purpose of a phase 2 study is to find out what effects,
      good and/or bad, MK-0646 has on metastatic neuroendocrine tumors.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with histologically or cytologically confirmed metastatic neuroendocrine
             tumors (NET)

          -  Patients must have histologically or cytologically confirmed well differentiated (low
             to intermediate grade) neuroendocrine tumors. High grade or poorly differentiated
             (i.e., large or small cell variant), Merkel cell, medullary carcinoma of the thyroid,
             and adrenal gland malignancies (including paragangliomas) are excluded from this
             study.

          -  Patient has at least one measurable lesion greater than or equal to 20 mm or greater
             than 10 mm on spiral CT.

          -  Patients who are on therapy with a somatostatin analogue are eligible for entry but
             must be on a stable dose for at least 3 months with no evidence of tumor shrinkage
             during that time period.

          -  Patient is male or female.

          -  Patient ≥ or equal to 18 years of age on the day of signing informed consent.

          -  Patient has performance status 0-2 on the ECOG Performance Scale.

          -  Patient has adequate organ function as indicated by the following laboratory values:

          -  Absolute Neutrophil Count (ANC) ≥ than or equal to 1,500/mcL

          -  platelets ≥ than or equal to 100,000/mcL

          -  Hemoglobin ≥ than or equal to 8 g/dL

          -  Serum Creatinine ≤ than or equal to 2 times the upper limit of normal (ULN)/ OR
             calculated CrCl ≥ than or equal to 60 mL/min (patients with creatinine levels ≥ than
             or equal to 2 times the ULN only). Patient may not be on dialysis

          -  Serum total bilirubin ≤ than or equal to 1.5 times the ULN

          -  AST (SGOT) and ALT (SGPT) ≤ than or equal to 5 times the ULN

          -  Prothrombin time (PT) Partial Thromboplastin time (PTT)

          -  ≤ than or equal to 1.2 times the ULN

          -  ≤than or equal to 1.2 times the ULN Creatinine clearance should be calculated by the
             Cockcroft-Gault method as follows:

          -  Male creatinine clearance = (140-age) x (weight in Kg)/(serum Cr x 72)

          -  Female creatinine clearance = ((140- age) x (weight in Kg)/(serum Cr x 72)) x 0.85

          -  Patient, or patient's legal representative, has voluntarily agreed to participate by
             giving written informed consent.

          -  Previous local therapy (e.g. chemoembolization or bland embolization) is allowed if
             completed > 6 weeks prior to study entry. For patients who received local therapy
             prior to study entry, there must be either documented growth of measurable disease
             within the embolization field or outside of the embolization field, or both, prior to
             study entry if the area of the embolization field was the only site of measurable
             disease.

          -  Previous chemotherapy, radiotherapy, and/or biologic therapy, including
             investigational agents, is/are allowed if completed > 4 weeks prior to study entry (>6
             weeks if last regimen contained BCNU or mitomycin C, and > 6 weeks from last dose of
             radiation therapy or radiopharmaceutical.

          -  Patients must not have disease that is currently amenable to curative surgery. Prior
             surgery is allowed no less than 6 weeks prior to study entry.

          -  Patients with diabetes mellitus are eligible for study entry but must have controlled
             diabetes as defined by hemoglobin A1c <8.0% within 2 weeks of initiation of protocol
             therapy.

        Exclusion Criteria:

          -  Patient has toxicities from prior therapies that have not resolved to grade 1 or grade
             0.

          -  Patient has known CNS metastases and/or carcinomatous meningitis.

          -  Patient has known primary central nervous system tumor.

          -  Patient has a known hypersensitivity to the components of study drug (MK-0646) or its
             analogs that is not treatable by premedication with antihistamines and steroids.

          -  Patient has a condition, including but not limited to, serious active infection,
             symptomatic congestive heart failure, unstable angina pectoris, serious cardiac
             arrhythmia, or major psychiatric illness, which, in the opinion of the treating
             investigator, is likely to confound the results of the study, or makes participation
             not in the best interest of the patient.

          -  Patient has a history of a prior active malignancy within the past 5 years, with the
             exception of cervical intraepithelial neoplasia; basal cell carcinoma of the skin,
             adequately treated localized prostate carcinoma with PSA <1.0, or squamous cell
             carcinoma of the skin removed (or the more superficial keratoacanthoma).

          -  Patient has known psychiatric or substance abuse disorders that would, in the opinion
             of the treating investigator, interfere with cooperation with the requirements of the
             trial.

          -  Patient is breastfeeding or pregnant (this will requires a negative test within 72
             hours of initiation of therapy), or expecting to conceive within the projected
             duration of the study.

          -  Patient is not using adequate contraception.

          -  Patient is known to be Human Immunodeficiency Virus (HIV)-positive.

          -  Patient has known active Hepatitis B or C.

          -  Patient is concurrently using growth hormone (GH), or growth hormone inhibitors.

          -  Patient has prior treatment with IGF-1R inhibitors.