Cetuximab and Everolimus in Treating Patients With Metastatic or Recurrent Colon Cancer or Head and Neck Cancer

NCT ID: NCT01637194

Last Updated: 2012-07-11

Study Results

Results pending

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.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-11-30

Study Completion Date

2011-07-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This phase I trial studies the side effects and best dose of cetuximab when given together with everolimus in treating patients with metastatic or recurrent colon cancer or head and neck cancer. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of the tumor to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Everolimus may stop the growth of tumor cells by blocking blood flow to the tumor. Giving cetuximab together with everolimus may be an effective treatment for colon cancer or head and neck cancer

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

PRIMARY OBJECTIVES:

I. Determine the safety, dose-limiting toxicity and maximum tolerated dose of daily RAD001 (everolimus) when given in combination with a fixed dose of weekly cetuximab in patients with solid tumors.

SECONDARY OBJECTIVES:

I. Determine whether a pharmacokinetic interaction exists between RAD001 and CETUXIMAB in patients treated with this regimen.

II. Determine preliminary clinical evidence of anti-tumor activity by time to progression and Response Evaluation Criteria in Solid Tumors (RECIST) criteria with this regimen.

III. Determine the association between clinical outcomes and biologic markers that may predict sensitivity of a tumor in patients treated with this regimen.

IV. Determine the pharmacodynamic effects of this regimen on post-therapy tumor and/or skin specimens.

OUTLINE: This is a dose-escalation study of everolimus.

Patients receive everolimus orally (PO) once daily (QD) on days -14 and then 1-28. Patients also receive cetuximab intravenously (IV) over 60-120 minutes on days -7 and then once weekly beginning on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2 months for at least 1 year.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Recurrent Adenoid Cystic Carcinoma of the Oral Cavity Recurrent Basal Cell Carcinoma of the Lip Recurrent Colon Cancer Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity Recurrent Lymphoepithelioma of the Nasopharynx Recurrent Lymphoepithelioma of the Oropharynx Recurrent Metastatic Squamous Neck Cancer With Occult Primary Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity Recurrent Mucoepidermoid Carcinoma of the Oral Cavity 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 Nasopharynx 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 Stage IV Adenoid Cystic Carcinoma of the Oral Cavity Stage IV Basal Cell Carcinoma of the Lip Stage IV Lymphoepithelioma of the Nasopharynx Stage IV Lymphoepithelioma of the Oropharynx Stage IV Mucoepidermoid Carcinoma of the Oral Cavity Stage IV Squamous Cell Carcinoma of the Hypopharynx Stage IV Squamous Cell Carcinoma of the Larynx 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 Stage IVA Colon Cancer Stage IVA Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity Stage IVA Inverted Papilloma of the Paranasal Sinus and Nasal Cavity Stage IVA Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity Stage IVA Salivary Gland Cancer Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity Stage IVB Colon Cancer Stage IVB Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity Stage IVB Inverted Papilloma of the Paranasal Sinus and Nasal Cavity Stage IVB Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity Stage IVB Salivary Gland Cancer Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity Stage IVC Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity Stage IVC Inverted Papilloma of the Paranasal Sinus and Nasal Cavity Stage IVC Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity Stage IVC Salivary Gland Cancer Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity Tongue Cancer

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Treatment (enzyme inhibitor, monoclonal antibody therapy)

Patients receive everolimus PO QD on days -14 and then 1-28. Patients also receive cetuximab IV over 60-120 minutes on days -7 and then once weekly beginning on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

everolimus

Intervention Type DRUG

Given PO

cetuximab

Intervention Type BIOLOGICAL

Given IV

pharmacological study

Intervention Type OTHER

Correlative studies

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

everolimus

Given PO

Intervention Type DRUG

cetuximab

Given IV

Intervention Type BIOLOGICAL

pharmacological study

Correlative studies

Intervention Type OTHER

laboratory biomarker analysis

Correlative studies

Intervention Type OTHER

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

42-O-(2-hydroxy)ethyl rapamycin Afinitor RAD001 C225 C225 monoclonal antibody IMC-C225 MOAB C225 monoclonal antibody C225 pharmacological studies

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Patients must have histologically-confirmed advanced solid tumors
* Patients who are refractory to standard therapy; patients with metastatic, irinotecan-refractory colon cancer, or recurrent/metastatic head and neck cancer may enroll, as cetuximab monotherapy is among the standard options for such patients; patients with locally advanced, treatment-naïve head and neck cancer who are candidates for radiation with cetuximab are not eligible, as radiation provides them a survival benefit, and the number of projected cetuximab doses would be only seven
* Development of new lesions or an increase in preexisting lesions on bone scintigraphy, computed tomography (CT), magnetic resonance imaging (MRI) or by physical examination; patients in whom the sole criterion for progression is an increase in a biochemical marker, e.g., carcinoembryonic antigen (CEA), or an increase in symptoms, are not eligible
* No radiotherapy (unless palliative), treatment with cytotoxic agents, or treatment with biologic agents =\< 3 weeks prior to registration on this study (6 weeks for mitomycin or nitrosoureas); \>= 2 weeks must have elapsed from any prior surgery or hormonal therapy; patients must have fully recovered from the acute toxicities of any prior treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities (returned to baseline status as noted before most recent treatment); patients with persisting, stable chronic toxicities from prior treatment =\< grade 1 are eligible
* Eastern Cooperative Oncology Group (ECOG) performance status =\<2 (Karnofsky \>= 60%)
* Life expectancy of \> 3 months
* Hemoglobin \>= 9 g/dL
* Leukocytes \>=3 K/mm\^3
* Absolute neutrophil count \>= 1.5 K/mm\^3
* Platelets \>= 100 K/mm\^3
* Total bilirubin within institutional normal limits
* Hepatitis B panel negative
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvate transaminase \[SGPT\]) =\< 2.5 X institutional upper limit of normal (ULN)
* Creatinine within 1.5 x ULN OR creatinine clearance \>= 50 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
* Women of child-bearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; complete abstinence) prior to study entry and for the duration of study participation and for 3 months after the conclusion of study therapy, and must have a negative serum or urine pregnancy test =\< 7 days prior to registration; pregnant and nursing patients are excluded because the side effects of the combination of cetuximab and RAD001 on a fetus or nursing child are unknown; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; sexually active men must also use appropriate contraception method and should not father a child while receiving therapy during this study
* Ability to understand and the willingness to sign a written informed consent document
* Fasting serum cholesterol \< 350 mg/d L and triglycerides \< 400 mg/d L
* Able and willing to undergo pharmacokinetic (PK) and pharmacodynamic (PD) testing as outlined in this protocol; if however the tumor is not amenable to the PD requirements of the protocol, the patient must be willing and able to undergo skin biopsy

Exclusion Criteria

* Chronic treatment with systemic steroids or another immunosuppressive agent
* Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
* Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
* Patients with an active, bleeding diathesis or on therapeutic anticoagulation (except low dose coumadin)
* Patients may not have received prior cetuximab therapy
* Patients may not be receiving any other investigational agents; in addition, patients must not have received investigational treatment =\< 30 days prior to registration
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in study
* Patients with chronic active hepatitis B or recent hepatitis B infection (hepatitis B surface antigen \[HepB sAg\] or immunoglobulin M \[IgM\] antibody to hepatitis B core antigen \[IgM antiBc\] positive) are ineligible because these patients are at increased risk of reactivation of the hepatitis B virus which may be fatal due to the immunosuppressive properties of RAD001
* Known human immunodeficiency virus (HIV)-positive patients are ineligible because these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy and the potential pharmacokinetic interaction between antiretroviral therapy and the investigational agents
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, oxygen dependent pulmonary disease or psychiatric illness/social situations that would limit compliance with study requirements; other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study (i.e., uncontrolled diabetes, uncontrolled hypertension, severe malnutrition, active ischemic heart disease, myocardial infarction within six months, chronic liver or renal disease, active upper gastrointestinal \[GI\] tract ulceration)
* All WOCBP MUST have a negative pregnancy test =\< 7 days prior to registration; if the pregnancy test is positive, the patient must not receive investigational product and must not be enrolled in the study
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Fox Chase Cancer Center

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Barbara Burtness

Role: PRINCIPAL_INVESTIGATOR

Fox Chase Cancer Center

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

NCI-2011-02971

Identifier Type: REGISTRY

Identifier Source: secondary_id

IRB 06-043

Identifier Type: -

Identifier Source: org_study_id