A Phase 1 Dose-escalation Study of OSI-906 and Erlotinib (Tarceva®)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT00739453
First received: August 19, 2008
Last updated: December 21, 2011
Last verified: December 2011
  Purpose

Multicenter, open-label, phase 1, cohort dose escalation study to determine the Maximum Tolerated Dose (MTD) of OSI-906 in combination with erlotinib


Condition Intervention Phase
Advanced Solid Tumors
Drug: OSI-906
Drug: erlotinib
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 OSI-906 and Erlotinib (Tarceva®) 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) and recommended phase 2 dose of OSI-906 and erlotinib [ Time Frame: 21 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety profile, Pharmacokinetic profile, pharmacodynamic activity, Preliminary antitumor activity [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Enrollment: 95
Study Start Date: October 2008
Study Completion Date: December 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Schedule 1
OSI-906 is administered on Days 1-3 every 7 days. Erlotinib will be administered daily starting on Day 2 of the initial treatment period and on Day 1-21 for all remaining treatment periods.
Drug: OSI-906
administered orally
Drug: erlotinib
administered orally
Other Names:
  • Tarceva
  • OSI-774
Experimental: Schedule 2
OSI-906 is administered daily starting on Day 1 and erlotinib is administered daily starting on Day 2 of the initial treatment period and on Day 1-21 for all remaining treatment periods.
Drug: OSI-906
administered orally
Drug: erlotinib
administered orally
Other Names:
  • Tarceva
  • OSI-774
Experimental: Schedule 3
OSI-906 is administered continuously twice daily starting on Day 1 and erlotinib is administered daily starting on Day 2. The NSCLC expansion cohort will follow Schedule 3 with the exception that erlotinib is administered daily starting on Day 8.
Drug: OSI-906
administered orally
Drug: erlotinib
administered orally
Other Names:
  • Tarceva
  • OSI-774

Detailed Description:

The study will open with Schedule 1 (S1), in which OSI-906 is administered on Days 1-3 every 7 days. Erlotinib will be administered daily starting on Day 2. A treatment period is defined as 21 days.

Initiation of Schedule 2 (S2), in which OSI-906 is administered daily starting on Day 1 and erlotinib is administered daily starting on Day 2, will occur after observation of clinically significant related toxicity >/= grade 2 in any patient on S1 or after > 2 dose levels in S1 have been examined without evidence of Dose Limiting Toxicities (DLT).

Initiation of Schedule 3 (S3), in which OSI-906 is administered twice daily starting on Day 1 and erlotinib is administered daily starting on Day 2, will occur after observation of clinically significant related toxicity >/= grade 2 in any patient on S2 or after > 2 dose levels in S2 have been examined without evidence of DLT.

Once the phase 2 dose has been established for S3, 1 expansion cohort will be opened.

The Expansion Cohort will enroll approximately 30 evaluable patients with stage IIIB/IV Non-small Cell Lung Carcinoma (NSCLC). Patients in the NSCLC Expansion Cohort will be required to have either archival tissue or fresh tumor tissue available at the start of study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed advanced solid tumor
  • For the NSCLC Expansion Cohort, a confirmed diagnosis of stage IIIB/IV NSCLC after failure of at least 1 prior chemotherapy regimen is required
  • Patients with Eastern Cooperative Oncology Group (ECOG) performance status </= 2
  • Predicted life expectancy >/= 12 weeks
  • Patients may have had prior therapy, providing certain conditions are met:

    1. 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. Patients must have recovered from any treatment-related toxicities (except for alopecia, fatigue, and grade 1 neurotoxicity) prior to registration.
    2. Hormonal therapy: Patients may have had prior anticancer hormonal therapy provided it is discontinued prior to registration into the 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.
    3. 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 radiation affected less than 25% of bone marrow.
    4. Surgery: Previous surgery is permitted provided that wound healing has occurred prior to registration.
  • Fasting glucose </= 125 mg/dL (7 mmol/L) at baseline and on Day 1 prior to dosing
  • Blood ketones </= Upper Limit of Normal (ULN)
  • Neutrophil count >/= 1.5 x 10^9/L
  • Platelets >/= 100 x 10^9/L
  • Bilirubin </= 1.5 x ULN
  • AST and/or ALT </= 2.5 x ULN or </= 5 x ULN if patient has documented liver metastases
  • Serum creatinine </= 1.5 x ULN
  • Patients must be nonsmokers (or former smokers who stopped smoking > 3 months previously) and have a negative cotinine test at baseline and on Day 1
  • Patients in the NSCLC Expansion Cohort must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST)
  • Patients in the NSCLC Expansion Cohort will be required to have either an archival or fresh tumor tissue (whole or partial block) available at the start of study
  • Patients must be accessible for repeat dosing and follow-up, including pharmacokinetic sampling
  • Patients - both males and females - with reproductive potential must agree to practice effective contraceptive measures throughout the study. Women of childbearing potential must provide a negative pregnancy test at baseline and on Day 1
  • Patients must provide verbal and 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)
  • History of cerebrovascular accident (CVA) within 12 months prior to registration or that is not stable
  • Prior epidermal growth factor receptor (EGFR) or insulin like growth factor receptor (IGFR) inhibitor therapy, except for prior erlotinib therapy in the NSCLC Expansion Cohort, prior erlotinib therapy will not be exclusionary
  • 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
  • Gastrointestinal (GI) abnormalities including inability to take oral medication, requirement for intravenous (IV) alimentation, active peptic ulcer, or prior surgical procedures affecting absorption
  • Ocular inflammatory or infectious condition that is not completely resolved prior to registration
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drug
  • Any type of active seizure disorder
  • Use of drugs that have a risk of causing QT interval prolongation within 14 days prior to Day 1 dosing
  • Use of strong or moderate CYP3A4 or CYP1A2 inhibitors/inducers, with the exception of low-dose steroids, within 14 days prior to Day 1 dosing
  • Use of proton pump inhibitors within 14 days prior to day 1 dosing
  • Symptomatic brain metastases that are not stable, require steroids, or that have required radiation within the last 28 days
  • Active or uncontrolled infections or serious illnesses or medical conditions that could interfere with the patient's ongoing participation in the study
  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: NCT00739453

Locations
United States, Colorado
University of Colorado Health Science Center
Aurora, Colorado, United States, 80045
United States, Maryland
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21231
United States, Michigan
Hudson-Webber Cancer Research Center, Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United Kingdom
University of Oxford Department of Medical Oncology
Oxford, United Kingdom, OX3 7LJ
Sponsors and Collaborators
Astellas Pharma Inc
Investigators
Study Director: Sr. Medical Director Astellas Pharma Global Development
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT00739453     History of Changes
Other Study ID Numbers: OSI-906-103, 2008-001743-20
Study First Received: August 19, 2008
Last Updated: December 21, 2011
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Astellas Pharma Inc:
Advanced cancer
Non-small cell lung cancer
Pancreatic cancer
Colorectal cancer
Prostate cancer

Additional relevant MeSH terms:
Erlotinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014