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

Sponsor

Astellas Pharma Inc (Industry)

Overall Status

Completed

CT.gov ID

NCT00739453

Collaborator

(none)

Enrollment

Locations

Arms

40.3

Actual Duration (Months)

23.8

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors	Drug: OSI-906 Drug: erlotinib	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

95 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (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

Actual Study Start Date :

Oct 23, 2008

Actual Primary Completion Date :

Mar 3, 2012

Actual Study Completion Date :

Mar 3, 2012

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Determine the maximum tolerated dose (MTD) and recommended phase 2 dose of OSI-906 and erlotinib [21 days]

Secondary Outcome Measures

Safety profile, Pharmacokinetic profile, pharmacodynamic activity, Preliminary antitumor activity [3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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
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

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado Health Science Center	Aurora	Colorado	United States	80045
2	Johns Hopkins Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland	United States	21231
3	Hudson-Webber Cancer Research Center, Karmanos Cancer Institute	Detroit	Michigan	United States	48201
4	University of Oxford Department of Medical Oncology	Oxford		United Kingdom	OX3 7LJ