Phase I/II Study of Postoperative Adjuvant Chemoradiation for Advanced-Stage Cutaneous Squamous Cell Carcinoma of the Head and Neck (cSCCHN)

NCT01465815 | Withdrawn Phase 1 DMC

• 2 other identifiers: 6901 (5466)NCI-2011-01225
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the side effects and best dose of linsitinib when given together with erlotinib hydrochloride and radiation therapy after surgery in treating patients with advanced or recurrent head and neck cancer. Erlotinib hydrochloride and linsitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy together with erlotinib hydrochloride and linsitinib may kill more tumor cells. Giving these treatments after surgery may kill any tumor cells that remain after surgery.

Conditions

Recurrent Skin Cancer; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Squamous Cell Carcinoma of the Skin; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity

Outcome Measures

Primary Outcomes (3)

• Number of participants with overall survival(OS) after two years of treatment (Phase II)

  The 2-year OS and 95% confidence interval will be determined using Kaplan-Meier method.

  Up to 2 years

• The maximum tolerated dose (MTD) of linsitinib when used in combination with erlotinib hydrochloride and radiation therapy (phase 1)

  The MTD of linsitinib when used in combination with erlotinib hydrochloride and radiation therapy will be determined using a standard 3x3 dose-escalation scheme. The dose limiting toxicity (DLT) will be defined according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v4.02). DLT is defined as any grade 3 non-hematologic toxicity attributed to treatment or grade 4 hematologic toxicity, neutropenic fever requiring hospitalization, or treatment delay due to hematologic toxicity.

  up to 24 months

• The maximum tolerated dose (MTD) of linsitinib when used in combination with erlotinib hydrochloride and radiation therapy (phase 1)

  The MTD of linsitinib when used in combination with erlotinib hydrochloride and radiation therapy will be determined using a standard 3x3 dose-escalation scheme. The dose limiting toxicity (DLT) will be defined according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events CTCAE (v4.02). DLT is defined as any grade 3 non-hematologic toxicity attributed to treatment or grade 4 hematologic toxicity, neutropenic fever requiring hospitalization, or treatment delay due to hematologic toxicity.

  Up to 5 years

Secondary Outcomes (6)

• Number of participants with disease free survival

  At 2 years

• Time to recurrence and patterns of failure

  Up to 2 years

• Effects of short-term preoperative treatment with erlotinib hydrochloride and linsitinib on the expression EGFR, IGF-1R and parallel or downstream molecular targets in cSCCHN in one third of the patients

  From baseline to time of surgery (after 7-14 days of study drug administration)

• Number of adverse events observed from linsitinib in combination with erlotinib hydrochloride and radiation therapy.

  After completion of study therapy at 6 and 12 weeks

• Number of adverse events observed from linsitinib in combination with erlotinib hydrochloride and radiation therapy

  Every 12-16 weeks for 2 years

Study Arms (3)

Treatment (adjuvant enzyme inhibitor and radiation therapy)

EXPERIMENTAL

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.

Drug: erlotinib hydrochloride; Drug: linsitinib; Radiation: radiation therapy; Procedure: therapeutic conventional surgery; Other: laboratory biomarker analysis

Erlotinib and Placebo (Sugar Pill)

EXPERIMENTAL

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.

Drug: erlotinib hydrochloride; Drug: placebo

OSI-906 and Placebo (Sugar Pill)

EXPERIMENTAL

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.

Drug: linsitinib; Drug: placebo

Interventions

erlotinib hydrochloride DRUG

Given PO

Also known as: CP-358,774, erlotinib, OSI-774

Erlotinib and Placebo (Sugar Pill); Treatment (adjuvant enzyme inhibitor and radiation therapy)

linsitinib DRUG

Given PO

Also known as: OSI-906

OSI-906 and Placebo (Sugar Pill); Treatment (adjuvant enzyme inhibitor and radiation therapy)

placebo DRUG

Given PO

Also known as: PLCB

Erlotinib and Placebo (Sugar Pill); OSI-906 and Placebo (Sugar Pill)

radiation therapy RADIATION

Undergo radiation therapy

Also known as: irradiation, radiotherapy, therapy, radiation

Treatment (adjuvant enzyme inhibitor and radiation therapy)

therapeutic conventional surgery PROCEDURE

Undergo planned surgery

Treatment (adjuvant enzyme inhibitor and radiation therapy)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (adjuvant enzyme inhibitor and radiation therapy)

Eligibility Criteria

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

You may qualify if:

• Patients must have primary or recurrent advanced-stage (III/IV) squamous cell carcinoma of the skin of the face, ear, scalp or neck or of the lip
• 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

You may not qualify if:

• Patients with known distant metastasis
• 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

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

MeSH Terms

Conditions

Skin Neoplasms

Interventions

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

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Therapeutics; Physical Phenomena

Study Officials

• Neil Gross

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 26, 2011
• First Posted: November 7, 2011
• Study Start: December 1, 2011
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: November 19, 2014

Record last verified: 2014-11

Locations

US (1)