Study of Continuous OSI-906 Dosing

Astellas

Status and phase

Completed

Phase 1

Conditions

Advanced Solid Tumors

Treatments

Drug: OSI-906

Study type

Interventional

Funder types

Industry

Identifiers

NCT00514007

OSI-906-101

2006-005937-39 (EudraCT Number)

Details and patient eligibility

About

Multicenter, open-label, phase 1, cohort dose escalation study to determine the Maximum Tolerated Dose (MTD) on both Once Daily (QD) and Twice Daily (BID) schedules.

Full description

Multicenter, open-label, phase 1, cohort dose escalation.

The study will open with the QD schedule, with initiation of the BID schedule occurring after observation of clinically significant related toxicity ≥ grade 2 in the QD schedule.

Dosing will be initiated on Day 1 with daily dosing (either QD or BID) continuing for 21 days.

Once the recommended phase 2 dose has been determined for the BID schedule, 2 expansion cohorts will be opened: 1) Biomarker Expansion Cohort in patients with locally advanced or metastatic colorectal cancer and 2) Diabetic Expansion Cohort in patients with advanced solid tumors who have active Type 2 diabetes mellitus not requiring insulin or insulinotropic therapy.

Enrollment

95 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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)