Phase I/II Study of Postoperative Adjuvant Chemoradiation for Advanced-Stage Cutaneous Squamous Cell Carcinoma of the Head and Neck (cSCCHN)
NCT ID: NCT01465815
Last Updated: 2014-11-19
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
WITHDRAWN
PHASE1/PHASE2
INTERVENTIONAL
2011-12-31
2013-09-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
I. To determine the MTD (maximally tolerated dose) of OSI-906 (linsitinib) when used in combination with erlotinib (erlotinib hydrochloride) and radiation therapy after surgery for advanced-stage cutaneous squamous cell carcinoma of the head and neck (cSCCHN). (Phase I) II. To estimate the 2-year overall survival (OS) compared to historical controls. (Phase II)
SECONDARY OBJECTIVES:
I. To determine the safety and tolerability of OSI-906 in combination with erlotinib and radiation therapy after surgery for advanced-stage cSCCHN.
II. To estimate the 2-year disease specific and disease free survival. III. To determine the time to recurrence and patterns of failure. IV. To evaluate the effects of short-term preoperative treatment with erlotinib and OSI-906 on the expression epidermal growth factor receptor (EGFR), insulin-like growth factor 1 receptor (IGF-1R) and parallel or downstream molecular targets in cSCCHN in one third of the patients.
OUTLINE:
Optional non-therapeutic (biomarker) portion: Patients are randomized to 1 of 3 treatment arms.
Arm A: Patients receive erlotinib hydrochloride orally (PO) once daily (QD) and linsitinib PO twice daily (BID) on days 1-7 or 1-14.
Arm B: Patients receive erlotinib hydrochloride PO QD and placebo PO QD or BID on days 1-7 or 1-14.
Arm C: Patients receive linsitinib PO BID and placebo PO QD or BID on days 1-7 or 1-14.
Treatment continues until 1 day before planned surgical resection (for up to 28 days if surgery is delayed).
Therapeutic portion: This is a phase I dose-escalation study of linsitinib followed by a phase II study.
Patients undergo standard QD conventional radiotherapy at the discretion of the treating physician. Patients receive concurrent linsitinib PO BID and erlotinib hydrochloride PO QD during the entire course of radiation in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 6 and 12 weeks, every 12-16 weeks for 2 years, every 6 months for 3 years, and then annually thereafter.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Treatment (adjuvant enzyme inhibitor and radiation therapy)
Optional non-therapeutic (biomarker) portion: Patients are randomized to 1 of 3 treatment arms.
Arm A: Patients receive erlotinib hydrochloride PO QD and linsitinib PO BID on days 1-7 or 1-14.
Treatment continues until 1 day before planned surgical resection (for up to 28 days if surgery is delayed).
Therapeutic portion: This is a phase I dose-escalation study of linsitinib followed by a phase II study.
Patients undergo standard QD conventional radiotherapy at the discretion of the treating physician. Patients receive concurrent linsitinib PO BID and erlotinib hydrochloride PO QD during the entire course of radiation in the absence of disease progression or unacceptable toxicity.
erlotinib hydrochloride
Given PO
linsitinib
Given PO
radiation therapy
Undergo radiation therapy
therapeutic conventional surgery
Undergo planned surgery
laboratory biomarker analysis
Correlative studies
Erlotinib and Placebo (Sugar Pill)
Arm B: Patients receive erlotinib hydrochloride PO QD and placebo PO QD or BID on days 1-7 or 1-14.
Treatment continues until 1 day before planned surgical resection (for up to 28 days if surgery is delayed).
Therapeutic portion: This is a phase I dose-escalation study of linsitinib followed by a phase II study.
Patients undergo standard QD conventional radiotherapy at the discretion of the treating physician. Patients receive concurrent linsitinib PO BID and erlotinib hydrochloride PO QD during the entire course of radiation in the absence of disease progression or unacceptable toxicity.
erlotinib hydrochloride
Given PO
placebo
Given PO
OSI-906 and Placebo (Sugar Pill)
Arm C: Patients receive linsitinib PO BID and placebo PO QD or BID on days 1-7 or 1-14.
Treatment continues until 1 day before planned surgical resection (for up to 28 days if surgery is delayed).
Therapeutic portion: This is a phase I dose-escalation study of linsitinib followed by a phase II study.
Patients undergo standard QD conventional radiotherapy at the discretion of the treating physician. Patients receive concurrent linsitinib PO BID and erlotinib hydrochloride PO QD during the entire course of radiation in the absence of disease progression or unacceptable toxicity.
linsitinib
Given PO
placebo
Given PO
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
erlotinib hydrochloride
Given PO
linsitinib
Given PO
placebo
Given PO
radiation therapy
Undergo radiation therapy
therapeutic conventional surgery
Undergo planned surgery
laboratory biomarker analysis
Correlative studies
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* A biopsy or preserved representative tumor block is required to confirm the diagnosis
* Patients must be surgical candidates with resectable disease; macroscopic complete resection of all tumor must be planned with curative intent
* Patients must be willing to receive postoperative radiation therapy and treatment with study drugs
* Both men and women and members of all races and ethnic groups will be included
* Life expectancy of greater than 12 months
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
* Absolute neutrophil count \>= 1,500/microliter(uL)
* Hemoglobin \>= 9 g/dL
* Platelets \>= 100,000/uL
* International normalized ratio (INR) \< institutional upper limit of normal (ULN)
* Total bilirubin =\< 1.5 x institutional ULN
* Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) =\< 2.5 X institutional ULN
* Creatinine =\< 1.5 X institutional ULN
* Fasting blood glucose \< 125 mg/dL at baseline
* Patients-both males and females-with reproductive potential (i.e., menopausal for less than 1 year and not surgically sterilized) must practice effective contraceptive measures throughout the study; women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration
* Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria
* Patients who have had prior radiation treatment of the index cancer or area of disease
* Patients who have received any other investigational medication within 6 weeks of enrollment, or who are scheduled to receive an investigational drug during the course of the study
* Prior treatment with EGFR inhibitor for index cancer
* Prior treatment with an IGF-1R antagonist (small molecule inhibitor or antibody)
* Breast-feeding, pregnancy or of childbearing potential (including less than two years postmenopausal) and unable to confirm adequate contraception due to possible risk to fetus or infant
* Insulin-dependent and non-insulin dependent diabetes mellitus including any metformin or insulin use on an ongoing basis prior to enrollment
* Known severe hypersensitivity to erlotinib, other small molecule inhibitors of EGFR, or its excipients
* Hepatitis B or C infection (acute or chronic), known human immunodeficiency virus (HIV), or active uncontrolled infection, because of possible risk of lethal infection when treated with marrow suppressive therapy
* History of uncontrolled cardiac disease such as unstable angina pectoris, myocardial infarction within prior 6 months, untreated coronary artery disease, uncontrolled congestive heart failure, or cardiomyopathy with decreased ejection fraction
* Uncontrolled peptic or gastric ulcer disease or gastrointestinal bleeding within prior 6 months
* Corrected QT interval (QTc) \> 450 msec; congenital long QT syndrome or previous history of QTc prolongation as a result from other medication
* Presence of left bundle branch block (LBBB); QTc with Bazett's correction that is unmeasurable, or \>= 450 msec on screening electrocardiogram (EKG)
* Any concomitant medication that may cause QTc prolongation or concomitant medication that is associated with Torsades de Pointes
* Psychiatric illness/social situations that would limit compliance with study requirements
* Active smokers unwilling to quit smoking during treatment
* Use of the potent cytochrome P450 3A4 (CYP3A4) and cytochrome P450 1A2 (CYP1A2) inhibitors is not allowed; other less potent CYP3A4 and CYP1A2 inhibitors/inducers are not excluded
* Participation in another investigational trial while on this study is not allowed
* History of poorly controlled gastrointestinal disorders including acute diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, Crohn's disease, ulcerative colitis or other diseases which have the potential for bowel perforation
* Other malignancies except for resected cervical cancer in situ
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Cancer Institute (NCI)
NIH
OHSU Knight Cancer Institute
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Neil Gross
Role: PRINCIPAL_INVESTIGATOR
OHSU Knight Cancer Institute
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
OHSU Knight Cancer Institute
Portland, Oregon, United States
Countries
Review the countries where the study has at least one active or historical site.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
NCI-2011-01225
Identifier Type: REGISTRY
Identifier Source: secondary_id
6901 (5466)
Identifier Type: -
Identifier Source: org_study_id