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A Phase I Dose Escalation Study of Intermittent Oral OSI-906 Dosing in Patients With Advanced Solid Tumors

Phase 1
18 Years
Not Enrolling
Advanced Solid Tumors

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Trial Information

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. 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.

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
- 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

- 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

- 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

- 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

- Pregnant or breast-feeding females

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to the study drug

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine the maximum tolerated dose (MTD) for each of 3 intermittent schedules and establish a recommended phase 2 dose of OSI-906

Outcome Time Frame:

14 days

Safety Issue:


Principal Investigator

Medical Monitor

Investigator Role:

Study Director

Investigator Affiliation:

Astellas Pharma Global Development


United States: Food and Drug Administration

Study ID:




Start Date:

June 2007

Completion Date:

December 2010

Related Keywords:

  • Advanced Solid Tumors
  • Advanced Cancer
  • Breast cancer
  • Renal cancer
  • Ovarian Cancer
  • Metastatic Cancer
  • Non-small cell lung cancer
  • Colorectal cancer



MD Anderson Cancer CenterHouston, Texas  77030-4096