Everolimus, Erlotinib Hydrochloride, and Radiation Therapy in Treating Patients With Recurrent Head and Neck Cancer Previously Treated With Radiation Therapy

NCT01332279 | Withdrawn Phase 1

• 1 other identifier: OER-HN-038
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of giving everolimus (RAD001) and erlotinib hydrochloride together with radiation therapy in treating patients with recurrent head and neck cancer previously treated with radiation therapy. RAD001 and erlotinib hydrochloride 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 RAD001 and erlotinib hydrochloride together with radiation therapy may kill more tumor cells.

Conditions

Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Tongue Cancer

Outcome Measures

Primary Outcomes (1)

• MTD of RAD001, erlotinib and radiotherapy in the re-irradiation setting

  Establish the safety profile of this regimen and establish the MTD of RAD001 with/without erlotinib in conjunction with RT.

  During the period of radiation treatment or within the first 2 weeks after the completion of radiotherapy

Secondary Outcomes (3)

• Preliminary data on response rate

  At 5 and 13 weeks post-radiation therapy and then every 3 months until disease progression or until patient comes off study

• Overall survival

  every 6 months

• Biological features of recurrent or second primary tumors, as well as surrogates of mTOR, EGFR and HIF-1α inhibition

  At baseline and week 4

Study Arms (1)

Treatment (enzyme inhibitor and radiation therapy)

EXPERIMENTAL

Patients receive RAD001 PO and erlotinib hydrochloride PO QD. Treatment continues for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo EBRT BID 5 days a week for 5 weeks.

Drug: everolimus; Drug: erlotinib hydrochloride; Procedure: biopsy; Other: laboratory biomarker analysis; Other: immunohistochemistry staining method; Genetic: polyacrylamide gel electrophoresis; Other: pharmacological study; Radiation: external beam radiation therapy; Genetic: microarray analysis

Interventions

everolimus DRUG

Given PO

Also known as: RAD001, Afinitor, 42-O-(2-hydroxy)ethyl rapamycin

Treatment (enzyme inhibitor and radiation therapy)

erlotinib hydrochloride DRUG

Given PO

Also known as: erlotinib, TARCEVA, OSI-774

Treatment (enzyme inhibitor and radiation therapy)

biopsy PROCEDURE

Correlative studies

Also known as: biopsies

Treatment (enzyme inhibitor and radiation therapy)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (enzyme inhibitor and radiation therapy)

immunohistochemistry staining method OTHER

Correlative studies

Also known as: immunohistochemistry

Treatment (enzyme inhibitor and radiation therapy)

polyacrylamide gel electrophoresis GENETIC

Correlative studies

Also known as: electrophoresis, polyacrylamide gel

Treatment (enzyme inhibitor and radiation therapy)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (enzyme inhibitor and radiation therapy)

external beam radiation therapy RADIATION

Undergo EBRT

Also known as: EBRT

Treatment (enzyme inhibitor and radiation therapy)

microarray analysis GENETIC

Correlative studies

Also known as: gene expression profiling

Treatment (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:

• Recurrent aerodigestive cancers of squamous cell histology of the head and neck, or those who have a second head and neck primary cancer, who have received prior radiation therapy for a head and neck malignancy with curative intent
• Patients must locally advanced disease, without distant metastases; measurable disease as per Response Evaluation Criteria In Solid Tumors (RECIST) is not required
• Patients who had surgery for recurrent disease or a second primary in a previously radiated field are eligible if their surgical pathology specimen from the resection exhibits high risk features such as positive margins or extracapsular extension
• Patient may have more than one recurrence as long as the current recurrence occurs at least \>= 6 months after the end of prior radiation therapy
• Only one prior course of radiotherapy to the head and neck region is allowed; prior chemotherapy is allowed
• Based on prior radiation treatment records, most (\> 50%) of the tumor volume must have been in areas previously irradiated to \>= 45 Gy without exceeding spinal cord tolerance (combining previous and future radiation dose to the spinal cord of =\< 50 Gy)
• The previous total radiation dose must not have exceeded a maximum dose of 75 Gy
• Karnofsky Performance Status \> 70 or Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
• Patients must sign study-specific informed consent and Health Insurance Portability and Accountability Act (HIPAA) forms
• Patient must be willing to have percutaneous endoscopic gastrostomy (PEG) placement if necessary
• Patients must be able to swallow oral medications
• Patients and/or their partners of childbearing potential are required to use adequate birth control during and for 6 months after completion of study therapy
• Leukocytes \>= 3,000/ul
• Absolute neutrophil count \>= 1,500/ul
• Platelets \>= 100,000/ul

You may not qualify if:

• Patient has history of using erlotinib or any other EGFR inhibitors (prior C225/Cetuximab treatment is allowed if given with radiation therapy, but treatment must have been completed at least 6 months prior to study entry)
• Patient has history of receiving RAD001 or any other mTOR inhibitors
• Patient is known to be allergic to any type of EGFR tyrosine kinase inhibitors or mTOR inhibitors
• Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent; topical or inhaled corticosteroids are allowed
• As judged by the investigator, any evidence of severe or uncontrolled psychiatric or systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease); history of noncompliance to medical regimens
• Pregnant or breast-feeding women or adults of reproductive potential who are not using effective birth control methods; adequate contraception must be used throughout the trial and for 8 weeks after the last dose of study drug, by both sexes; (women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of RAD001)
• Concomitant use of phenytoin, carbamazepine, rifampicin, barbiturates, or St John's Wort; these medications can be discontinued one week prior to enrollment if medically feasible
• Treatment on any other clinical protocols or with a non-approved or investigational drug within 4 weeks before Day 1 of study treatment
• Any evidence of clinically active interstitial lung disease (patients with chronic stable radiographic changes who are asymptomatic need not be excluded)
• Known active connective tissue disorders, such as lupus or scleroderma which, in the opinion of the treating physician, may put the patient at high risk for radiation toxicity
• Patients with known human immunodeficiency virus (HIV) infection and/or acquired immune deficiency (AIDS)
• Patients with known multiple sclerosis
• Patients with nasopharyngeal carcinoma are excluded; other malignancies within the past 3 years which actively require ongoing treatment except for treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin
• Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period; close contact with those who have received attenuated live vaccines should be avoided during treatment with RAD001; examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, Bacillus Calmette-Guerin (BCG), yellow fever, varicella and TY21a typhoid vaccines
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:

Sponsors & Collaborators

• Fox Chase Cancer Center: lead

Study Sites (1)

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

MeSH Terms

Conditions

Salivary Gland Neoplasms; Squamous Cell Carcinoma of Head and Neck; Tongue Neoplasms

Interventions

Everolimus; Erlotinib Hydrochloride; Biopsy; Immunohistochemistry; Electrophoresis, Polyacrylamide Gel; Microarray Analysis; Gene Expression Profiling

Condition Hierarchy (Ancestors)

Mouth Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Mouth Diseases; Stomatognathic Diseases; Salivary Gland Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Tongue Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Histocytochemistry; Histological Techniques; Immunologic Techniques; Electrophoresis; Chemistry Techniques, Analytical; Electrochemical Techniques; Microchip Analytical Procedures; Genetic Techniques

Study Design

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

Study Record Dates

• First Submitted: April 7, 2011
• First Posted: April 11, 2011
• Study Start: April 1, 2011
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: April 4, 2023

Record last verified: 2023-03

Locations

US (1)