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

This study has been terminated.
(Drug manufacturer, Astellas Pharma, informed us that safety and efficacy of Erlotinib and OSI-906 in other oncology studies was determined to be unfavorable.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT01465815
First received: October 26, 2011
Last updated: March 6, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
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
Drug: erlotinib hydrochloride
Drug: linsitinib
Drug: placebo
Radiation: radiation therapy
Procedure: therapeutic conventional surgery
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of Postoperative Adjuvant Chemoradiation for cSCCHN

Resource links provided by NLM:


Further study details as provided by OHSU Knight Cancer Institute:

Primary Outcome Measures:
  • Number of participants with overall survival(OS) after two years of treatment (Phase II) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    The 2-year OS and 95% confidence interval will be determined using Kaplan-Meier method.

  • The maximum tolerated dose (MTD) of linsitinib when used in combination with erlotinib hydrochloride and radiation therapy (phase 1) [ Time Frame: up to 24 months ] [ Designated as safety issue: Yes ]
    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.

  • The maximum tolerated dose (MTD) of linsitinib when used in combination with erlotinib hydrochloride and radiation therapy (phase 1) [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Number of participants with disease free survival [ Time Frame: At 2 years ] [ Designated as safety issue: No ]
  • Time to recurrence and patterns of failure [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: From baseline to time of surgery (after 7-14 days of study drug administration) ] [ Designated as safety issue: No ]
  • Number of adverse events observed from linsitinib in combination with erlotinib hydrochloride and radiation therapy. [ Time Frame: After completion of study therapy at 6 and 12 weeks ] [ Designated as safety issue: Yes ]
  • Number of adverse events observed from linsitinib in combination with erlotinib hydrochloride and radiation therapy [ Time Frame: Every 12-16 weeks for 2 years ] [ Designated as safety issue: Yes ]
  • Number of adverse events observed from linsitinib in combination with erlotinib hydrochloride and radiation therapy [ Time Frame: Every 6 months for 3 years and then annually thereafter ] [ Designated as safety issue: Yes ]

Enrollment: 67
Study Start Date: December 2011
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

Drug: erlotinib hydrochloride
Given PO
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
Drug: linsitinib
Given PO
Other Name: OSI-906
Radiation: radiation therapy
Undergo radiation therapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Procedure: therapeutic conventional surgery
Undergo planned surgery
Other: laboratory biomarker analysis
Correlative studies
Experimental: 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.

Drug: erlotinib hydrochloride
Given PO
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
Drug: placebo
Given PO
Other Name: PLCB
Experimental: 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.

Drug: linsitinib
Given PO
Other Name: OSI-906
Drug: placebo
Given PO
Other Name: PLCB

Detailed Description:

PRIMARY OBJECTIVES:

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.

  Eligibility

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

Inclusion Criteria:

  • 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/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 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
  • 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
  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: NCT01465815

Locations
United States, Oregon
OHSU Knight Cancer Institute
Portland, Oregon, United States, 97239
Sponsors and Collaborators
OHSU Knight Cancer Institute
Investigators
Principal Investigator: Neil Gross OHSU Knight Cancer Institute
  More Information

No publications provided

Responsible Party: OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT01465815     History of Changes
Other Study ID Numbers: 6901 (5466), NCI-2011-01225
Study First Received: October 26, 2011
Last Updated: March 6, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Skin Neoplasms
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Skin Diseases
Neoplasms, Squamous Cell
Erlotinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 11, 2014