Study of Intermittent OSI-906 Dosing

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00514306
Recruitment Status : Completed
First Posted : August 9, 2007
Last Update Posted : September 13, 2011
Information provided by (Responsible Party):
Astellas Pharma Inc

August 7, 2007
August 9, 2007
September 13, 2011
June 2007
December 2010   (Final data collection date for primary outcome measure)
Determine the maximum tolerated dose (MTD) for each of 3 intermittent schedules and establish a recommended phase 2 dose of OSI-906 [ Time Frame: 14 days ]
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Complete list of historical versions of study NCT00514306 on Archive Site
Safety profile, Pharmacokinetic profile, Pharmacodynamic relationships Preliminary antitumor activity [ Time Frame: 3 years ]
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Study of Intermittent OSI-906 Dosing
A Phase I Dose Escalation Study of Intermittent Oral OSI-906 Dosing in Patients With Advanced Solid Tumors
Multicenter, open-label, phase 1, cohort dose escalation study to determine the maximum tolerated dose (MTD) of 3 intermittent OSI-906 dosing schedules.

Multicenter, open-label, phase 1, cohort dose escalation. The study will open with Dosing Schedule 1 (S1) (OSI-906 Once Daily (QD) Days 1-3 every 14 days). Dosing Schedule 2 (S2) (OSI-906 QD Days 1-5 every 14 days) will be initiated following observation of clinically significant related toxicity ≥ grade 2 in S1 or after a review of preliminary safety and pharmacokinetic data from ≥ 6 dose levels in S1 indicate that toxicity is acceptable and potential improvement in exposure may be achieved by an increased number of dosing days. Dosing Schedule 3 (S3) (OSI-906 QD Days 1-7 every 14 days) will occur upon observation of clinically significant related toxicity ≥ grade 2 in S2 or after ≥ 1 dose level in S2 has been examined.

A 3-patient bridging dose cohort will be opened in S1 to qualitatively compare the 25 mg capsule with 100 mg capsule dosage strengths in order to confirm that no gross differences in safety or exposure exist between the formulations. In order to characterize the tablet, a 6-patient dose cohort will be opened to qualitatively examine the pharmacokinetics of this dosage form.

Once the MTD has been determined for S1 and once the safety and pharmacokinetic data from the tablet cohort have been reviewed, a Fed-Fasted Expansion Cohort will be opened.

Phase 1
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Advanced Solid Tumors
Drug: OSI-906
Oral OSI-906 administered on an intermittent schedule at increasing doses until disease progression or unacceptable toxicity
  • Experimental: Schedule 1
    OSI-906 days 1-3 every 14 days
    Intervention: Drug: OSI-906
  • Experimental: Schedule 2
    OSI-906 days 1-5 every 14 days
    Intervention: Drug: OSI-906
  • Experimental: Schedule 3
    OSI-906 days 1-7 every 14 days
    Intervention: Drug: OSI-906
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
December 2010
December 2010   (Final data collection date for primary outcome measure)

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 with Eastern Cooperative Oncology Group (ECOG) performance status </= 2
  • Predicted life expectancy ≥ 12 weeks
  • Patients may have had prior therapy, providing the following conditions are met:

    • Chemotherapy: A minimum of 3 weeks (4 weeks for carboplatin or investigational anticancer agents and 6 weeks for nitrosoureas and mitomycin C) must have elapsed between the end of treatment and registration into this study. Prior tyrosine kinase inhibitor therapy is permitted. Patients must have recovered from any treatment-related toxicities (except for alopecia, fatigue, and grade 1 neurotoxicity) prior to registration
    • Hormonal therapy: Patients may have had prior anticancer hormonal therapy provided it is discontinued prior to registration into this study. However, patients with prostate cancer with evidence of progressive disease may continue on therapy that produces medical castration (eg, goserelin or leuprorelin), provided this therapy was commenced at least 3 months earlier
    • Radiation: Patients may have had prior radiation therapy provided they have recovered from the acute, toxic effects of radiotherapy prior to registration. A minimum of 21 days must have elapsed between the end of radiotherapy and registration into the study unless the radiotherapy was palliative and nonmyelosuppressive
    • Surgery: Previous surgery is permitted provided that wound healing has occurred prior to registration
  • Fasting glucose ≤ 125 mg/dL (7 mmol/L) at baseline
  • 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
  • Adequate hematopoietic, hepatic, and renal function defined as follows:

    • Neutrophil count ≥ 1.5 x 10^9/L and platelet count ≥ 100 x 10^9/L
    • Bilirubin ≤ 1.5 x ULN or ≤ 3 x ULN if patient has Gilbert's disease
    • AST and/or ALT ≤ 2.5 x ULN or ≤ 5 x UNL if patient has documented liver metastases
    • Serum creatinine ≤ 1.5 x ULN
  • Patients must be accessible for repeat dosing and follow-up, including pharmacokinetic sampling
  • Patients - both males and females - with reproductive potential (ie, menopausal for less than 1 year and not surgically sterilized) must practice effective contraceptive measures (ie, barrier methods, eg, condom or diaphragm, with spermicide) throughout the study. Women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration
  • Patients must provide written informed consent to participate in the study

Exclusion Criteria:

  • Documented history of diabetes mellitus
  • History of significant cardiac disease unless the disease is well-controlled. Significant cardiac diseases includes second/third degree heart block; significant ischemic heart disease; QTc interval > 450 msec at baseline; poorly controlled hypertension; congestive heart failure of New York Heart Association (NYHA)Class II or worse (slight limitation of physical activity; comfortable at rest, but ordinary physical activity results in fatigue, palpitation, or dyspnea)
  • Any type of active seizure disorder
  • Concurrent anticancer therapy (with the exception of hormonal therapy as described above)
  • 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 dosing and while on study, with the exception of hormone replacement therapy or inhalers
  • History of any kind of stroke
  • Previously diagnosed brain metastases (includes active brain metastases)
  • Active or uncontrolled infections or serious illnesses or medical conditions that could interfere with the patient's ongoing participation in the study
  • History of any psychiatric condition that might impair the patient's ability to understand or to comply with the requirements of the study or to provide informed consent
  • Pregnant or breast-feeding females
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drug
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United Kingdom,   United States
2006-005938-20 ( EudraCT Number )
Not Provided
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Astellas Pharma Inc
Astellas Pharma Inc
Not Provided
Study Director: Medical Monitor Astellas Pharma Global Development
Astellas Pharma Inc
September 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP