Clinical trial NCT00514007 (phase 1, status: completed)
Conditions: advanced solid tumors
ICD codes: K74.02, G47.22, H35.3133, H35.3134, H35.3113, H35.3114, H35.3123
Drugs: osi-906
SMILES: C[C@@]1(O)C[C@@H](C1)C1=NC(=C2N1C=CN=C2N)C1=CC=C2C=CC(=NC2=C1)C1=CC=CC=C1
Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically documented malignancy that is now advanced and/or
             metastatic and refractory to established forms of therapy or for which no effective
             therapy exists. Patients in the Biomarker Expansion Cohort must have histologically
             documented colorectal cancer that is locally advanced or metastatic and refractory to
             established forms of therapy. These patients must have archival tissue available and a
             lesion accessible for biopsy

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2, life expectancy
             ≥ 12 weeks

          -  Prior chemotherapy is permitted provided that a minimum of 3 weeks has elapsed. Prior
             tyrosine kinase inhibitor therapy is permitted. Patients must have recovered from any
             treatment-related toxicities (with some exceptions) prior to registration

          -  Prior hormonal therapy is permitted provided it is discontinued prior to registration
             (with the exception of prostate cancer patients who have been on hormone therapy for
             at least 3 months)

          -  Prior radiation therapy is permitted provided that patients have recovered from the
             toxic effects. A minimum of 21 days must have elapsed unless the radiotherapy was
             palliative and nonmyelosuppressive

          -  Prior surgery is permitted provided that wound healing has occurred prior to
             registration

          -  Fasting glucose ≤ 125 mg/dL (7 mmol/L) at baseline (all patients except those in the
             Diabetic Expansion Cohort). Patients in the Diabetic Expansion Cohort must have a
             fasting glucose of ≤ 150 mg/dL (8.3 mmol/L) at baseline. If patients in the Diabetic
             Expansion Cohort are being treated with non-insulinotropic oral antihyperglycemic
             therapy, doses must be stable for ≥ 4 weeks prior to registration

          -  Potassium, calcium, and magnesium must be within normal limits (WNL). Electrolyte
             abnormalities will be permitted if they are not clinically significant and if
             treatment for the abnormality is initiated prior to Day 1

          -  Neutrophil ≥ 1.5 x 10^9/L, Platelet (PLT) ≥ 100 x 10^9/L; bilirubin ≤ 1.5 x upper
             limit of normal (ULN), AST and ALT ≤ 2.5 x ULN or ≤ 5 x UNL if patient has documented
             liver metastases; creatinine ≤ 1.5 x ULN

          -  Accessible for repeat dosing and follow-up, including pharmacokinetic sampling

          -  Patients must practice effective contraceptive measures throughout the study

          -  Provide written informed consent

        Exclusion Criteria:

          -  History of any kind of stroke

          -  History of any psychiatric condition that might impair the patient's ability to
             provide informed consent or participate

          -  History of allergic reaction attributed to a similar compound as study drug.

          -  Any type of active seizure disorder

          -  Previously diagnosed brain metastases

          -  Concurrent anticancer therapy

          -  Active or uncontrolled infections of serious illnesses or medical conditions that
             could interfere with participation

          -  Pregnant or breast-feeding females

          -  Documented history of diabetes mellitus (all patients except those in the Diabetic
             Expansion Cohort). Patients in the Diabetic Expansion Cohort may not have Type 1
             diabetes mellitus or Type 2 diabetes mellitus currently requiring insulinotropic or
             insulin therapy

          -  Use of drugs with a risk of causing QT interval prolongation within 14 days prior to
             Day 1 and while on study

          -  Use of glucocorticoids within 14 days prior to Day 1 and while on study

          -  History of significant cardiac disease unless well controlled (includes 2nd/3rd degree
             heart block, ischemic heart disease, QTc > 450 msec, poorly controlled hypertension,
             or congestive heart failure of New York Heart Association (NYHA) Class II or worse)