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A Phase I Evaluation of Cetuximab and RAD001 in Patients With Solid Tumors


Phase 1
18 Years
N/A
Not Enrolling
Both
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

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Trial Information

A Phase I Evaluation of Cetuximab and RAD001 in Patients With Solid Tumors


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.


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of patients with dose limiting toxicity

Outcome Description:

Dose-limiting toxicity defined as any grade 3 or greater non-hematologic, grade 4 thrombocytopenia, grade 4 neutropenia lasting more than 5 days, grade 4 febrile neutropenia requiring hospitalization or treatment delay more than 2 weeks due to unresolved toxicity.

Outcome Time Frame:

Day -14 through Day 28 of Cycle 1

Safety Issue:

Yes

Principal Investigator

Barbara Burtness

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fox Chase Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

IRB 06-043

NCT ID:

NCT01637194

Start Date:

November 2008

Completion Date:

July 2011

Related Keywords:

  • 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
  • Carcinoma
  • Colonic Neoplasms
  • Carcinoma, Basal Cell
  • Carcinoma, Squamous Cell
  • Carcinoma, Adenoid Cystic
  • Granuloma
  • Head and Neck Neoplasms
  • Laryngeal Diseases
  • Papilloma
  • Tongue Neoplasms
  • Carcinoma, Mucoepidermoid
  • Carcinoma, Verrucous
  • Esthesioneuroblastoma, Olfactory
  • Papilloma, Inverted
  • Neoplasms, Unknown Primary
  • Salivary Gland Neoplasms
  • Hypopharyngeal Neoplasms
  • Laryngeal Neoplasms
  • Paranasal Sinus Neoplasms
  • Oropharyngeal Neoplasms
  • Nasopharyngeal Neoplasms

Name

Location

Fox Chase Cancer Center Philadelphia, Pennsylvania  19111