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

NCT00739453 | Completed Phase 1 FDA Drug

• 2 other identifiers: OSI-906-1032008-001743-20
• Study Type: interventional
• Target: 95
• Locations: 2 countries
• Sites: 4

Brief Summary

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

Conditions

Advanced Solid Tumors

Keywords

Pancreatic cancer; Advanced cancer; Prostate cancer; Non-small cell lung cancer; Colorectal cancer

Outcome Measures

Primary Outcomes (1)

• Determine the maximum tolerated dose (MTD) and recommended phase 2 dose of OSI-906 and erlotinib

  21 days

Secondary Outcomes (1)

• Safety profile, Pharmacokinetic profile, pharmacodynamic activity, Preliminary antitumor activity

  3 years

Study Arms (3)

Schedule 1

EXPERIMENTAL

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; Drug: erlotinib

Schedule 2

EXPERIMENTAL

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; Drug: erlotinib

Schedule 3

EXPERIMENTAL

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; Drug: erlotinib

Interventions

OSI-906 DRUG

administered orally

Schedule 1; Schedule 2; Schedule 3

erlotinib DRUG

administered orally

Also known as: Tarceva, OSI-774

Schedule 1; Schedule 2; Schedule 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.
• 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.
• 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.
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Astellas Pharma Inc: lead

Study Sites (4)

University of Colorado Health Science Center

Aurora, Colorado, 80045, United States

Location

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

Hudson-Webber Cancer Research Center, Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

University of Oxford Department of Medical Oncology

Oxford, OX3 7LJ, United Kingdom

Location

Related Links

• Link to results on Astellas Clinical Study Results website

MeSH Terms

Conditions

Pancreatic Neoplasms; Prostatic Neoplasms; Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms

Interventions

3-(8-amino-1-(2-phenylquinolin-7-yl)imidazo(1,5-a)pyrazin-3-yl)-1-methylcyclobutanol; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Sr. Medical Director

  Astellas Pharma Global Development

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2008
• First Posted: August 21, 2008
• Study Start: October 23, 2008
• Primary Completion: March 3, 2012
• Study Completion: March 3, 2012
• Last Updated: November 20, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.

Locations

US (3); GB (1)