A Phase II Clinical and Translational Study of MK-0646 in Patients With Metastatic Neuroendocrine Tumors (NET)
- Patients with histologically or cytologically confirmed metastatic neuroendocrine
- 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
- 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
- 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
- Patient has toxicities from prior therapies that have not resolved to grade 1 or
- 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
- 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.