Study of Continuous OSI-906 Dosing

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT00514007
First received: August 7, 2007
Last updated: April 16, 2012
Last verified: April 2012
  Purpose

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.


Condition Intervention Phase
Advanced Solid Tumors
Drug: OSI-906
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Dose Escalation Study of Continuous Oral OSI-906 Dosing in Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Determine the maximum tolerated dose (MTD) for both the once daily (QD) and twice daily (BID) dosing schedules and establish a recommended phase 2 dose of oral OSI-906 [ Time Frame: 21 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety profile; Pharmacokinetic (PK) profile; Pharmacodynamic relationships and preliminary antitumor activity [ Time Frame: 2.5 years ] [ Designated as safety issue: Yes ]

Enrollment: 95
Study Start Date: December 2006
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: OSI-906 QD
Once per day
Drug: OSI-906
OSI-906 administered orally
Experimental: OSI-906 BID
Twice per day
Drug: OSI-906
OSI-906 administered orally

Detailed 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.

This study is currently only recruiting to the Biomarker and Diabetic Expansion Cohorts.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00514007

Locations
United States, Tennessee
Vanderbilt Universtiy Medical Center
Nashville, Tennessee, United States, 37232-6307
United Kingdom
The Beatson West of Scotland Cancer Centre
Glasgow, United Kingdom, G12 0YN
Sponsors and Collaborators
Astellas Pharma Inc
Investigators
Study Director: Medical Director Astellas Pharma Global Development
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT00514007     History of Changes
Other Study ID Numbers: OSI-906-101, 2006-005937-39
Study First Received: August 7, 2007
Last Updated: April 16, 2012
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Astellas Pharma Inc:
Non-small cell lung cancer
Ovarian cancer
Renal cancer
Advanced Cancer
Metastatic cancer
Breast cancer
Colorectal cancer

ClinicalTrials.gov processed this record on July 31, 2014