Erlotinib Hydrochloride and Radiation Therapy in Stage III-IV Squamous Cell Cancer of the Head and Neck

NCT01192815 | Terminated Phase 2 Results DMC

• 2 other identifiers: CASE2309NCI-2010-01885
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Erlotinib hydrochloride may also make tumor cells more sensitive to radiation therapy. Radiation therapy uses high-energy x- rays and other types of radiation to kill tumor cells. Giving erlotinib hydrochloride together with radiation therapy may be an effective treatment for patients with head and neck cancer.PURPOSE: This phase II trial is studying how well giving erlotinib hydrochloride together with radiation therapy works in treating patients with stage III-IV squamous cell cancer of the head and neck.

Conditions

Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity

Outcome Measures

Primary Outcomes (1)

• Time to Disease Progression

  The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever status is recorded first) until the first date that recurrence or PD is objectively documented, taking as reference for PD the smallest measurements recorded since the treatment started. Disease progression free survival (PFS) is measured from start of treatment to the date of disease progression or protocol-designated outcome, whichever occurs first and censored at the date of last followed for those survivors without disease progression Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Measured via Conventional CT and MRI

  1 year and 10 months following study start

Secondary Outcomes (5)

• Objective Response Rate

  1 year and 10 months following study start

• Patterns of Failure

  5 yrs following treatment

• Toxicities, Number of Persons With Adverse Events

  up to 2 yrs after treatment

• Quality of Life Assessment as Measured by Functional Assessment of Cancer Therapy (FACT-G) Test

  after treatment at 6 mos

• Locoregional Control Rate

  5 yrs following treatment

Other Outcomes (2)

• Pharmacokinetic Data

  pre-treatment then weekly

• Lab Correlates

  2 yrs post concurrent chemo-radiation therapy

Study Arms (1)

Arm I

EXPERIMENTAL

Patients receive erlotinib hydrochloride orally or via gastrostomy tube once daily in weeks 1-9 and then for 2 years following completion of radiation therapy. Beginning on day 1 of week 2, patients undergo radiation therapy once daily, 5 times a week, for 5-7 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

Drug: erlotinib hydrochloride; Radiation: intensity-modulated radiation therapy; Other: pharmacogenomic studies; Other: gene expression analysis; Radiation: 3-dimensional conformal radiation therapy; Other: biopsy; Other: pharmacological study; Other: laboratory biomarker analysis; Other: questionnaire administration; Other: enzyme-linked immunosorbent assay; Other: polymorphism analysis

Interventions

erlotinib hydrochloride DRUG

Given orally or via gastronomy tube

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

Arm I

intensity-modulated radiation therapy RADIATION

IMRT will be given in 35 fractions over 7 weeks. The primary tumor and involved nodes (PTV70) will receive 2 Gy per fractions, intermediate-risk areas (PTV63) will receive 1.8 Gy per fractions, and subclinical disease sites (PTV56) will receive 1.6 Gy perfraction. The total doses will thus be 70 Gy, 63 Gy and 56 Gy, respectively.

Also known as: IMRT

Arm I

pharmacogenomic studies OTHER

Optional correlative studies

Also known as: Pharmacogenomic Study

Arm I

gene expression analysis OTHER

Correlative studies

Arm I

3-dimensional conformal radiation therapy RADIATION

The initial target volume encompassing the gross and subclinical disease sites will receive 2.0 Gy per fraction, five fractions a week to 54 Gy in 27 fractions in 5.4 weeks. The boost volume covering gross tumor and clinically/radiologically involved nodes will receive boost irradiation for additional 16 Gy at 2.0 Gy. The primary tumor and clinically/radiologically-involved nodes will thus receive 70 Gy in 35 fractions over 7 weeks, and uninvolved upper neck nodes will receive an elective dose of 54 Gy in 5.4 weeks. The uninvolved lower neck nodes will receive 2.0 Gy per fraction at 3-cm depth to a total dose of 50 Gy in 25 fractions in 5.0 weeks through a matching AP or AP/PA lower neck field.

Also known as: 3D-CRT, conformal radiation therapy

Arm I

biopsy OTHER

Optional correlative studies

Also known as: biopsies

Arm I

pharmacological study OTHER

Optional correlative studies

Also known as: pharmacological studies

Arm I

laboratory biomarker analysis OTHER

Optional correlative studies

Arm I

questionnaire administration OTHER

Optional ancillary studies

Arm I

enzyme-linked immunosorbent assay OTHER

Optional correlative studies

Also known as: ELISA

Arm I

polymorphism analysis OTHER

Optional correlative studies

Arm I

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed locally advanced (stage III or IV) squamous cell carcinoma of the head and neck without distant metastatic disease, who are not candidates or have declined definitive surgical resection or for administration of standard chemotherapy during radiation therapy because of any of the following reasons: advanced age (\>= 70 years); poor ECOG performance status (2 or 3); significant comorbidities, as reflected by a Charlson comorbidity index score of \>= 3; abnormal hematopoietic, hepatic or renal function; patient's decision after applicable standard treatment options have been offered and declined by patient
• No prior chemotherapy, radiation therapy, or investigational antitumor drug
• Measurable disease within 4 weeks prior to registration according to the recommended RECIST response criteria
• Life expectancy of greater than 12 weeks
• Patients must have normal hepatic function or well compensated liver disease as defined by the Child-Pugh classification of severity of liver disease; patients with hepatic impairment (total bilirubin greater than upper limit of normal \[ULN\] or well-compensated disease \[Child-Pugh class A\] enrolled in the trial will be closely monitored, especially those with total bilirubin \> 3 times ULN; dosage modifications (therapy interruption or discontinuation) may be necessary for severe changes in liver function; patient management will follow the FDA-approved labeling recommendations
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation
• Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter
• Women of childbearing potential must have a negative pregnancy test; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Ability to understand and willingness to sign a written informed consent document

You may not qualify if:

• All histologies other than squamous cell carcinoma
• Salivary gland paranasal sinus and nasopharyngeal squamous cell carcinoma
• Patients who have had prior chemotherapy or radiotherapy
• Patients with metastatic disease
• Patients with ECOG performance status of 4
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ERLOTINIB
• Patients with history of any other malignancy (except squamous cell or basal cell cancer of the skin or CIS of cervix) are ineligible unless a period of 5 years has elapsed since treatment of the previous cancer and the patient is currently disease-free from the previous cancer
• Patients may not be receiving any other investigational agent
• Pregnant women; breastfeeding should be discontinued

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Erlotinib Hydrochloride; Radiotherapy, Intensity-Modulated; Pharmacogenomic Testing; Gene Expression Profiling; Radiotherapy, Conformal; Biopsy; Enzyme-Linked Immunosorbent Assay; Amplified Fragment Length Polymorphism Analysis

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Genetic Testing; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services; Cytodiagnosis; Cytological Techniques; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Immunoenzyme Techniques; Immunoassay; Immunologic Techniques; Immunosorbent Techniques; Immunohistochemistry; Molecular Probe Techniques; DNA Fingerprinting; Polymerase Chain Reaction; Nucleic Acid Amplification Techniques

Limitations and Caveats

Study funding unavailable therefore study terminated early. Both patients did not complete treatment per protocol and were not evaluable.

Results Point of Contact

• Title: Panayiotis Savvides, MD
• Organization: Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Panayiotis.Savvides@uhhospitals.org

216-844-5946

Study Officials

• Panayiotis Savvides, MD

  Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2010
• First Posted: September 1, 2010
• Study Start: January 1, 2011
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: May 12, 2020
• Results First Posted: May 12, 2020

Record last verified: 2020-05

Locations

US (1)