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

July 6, 2012 updated by: Fox Chase Cancer Center

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111-2497
        • Fox Chase Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 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.
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Names:
  • pharmacological studies
Biological: cetuximab
Given IV
Other Names:
  • C225
  • IMC-C225
  • C225 monoclonal antibody
  • MOAB C225
  • monoclonal antibody C225
Drug: everolimus
Given PO
Other Names:
  • Afinitor
  • RAD001
  • 42-O-(2-hydroxy)ethyl rapamycin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with dose limiting toxicity
Time Frame: Day -14 through Day 28 of Cycle 1
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.
Day -14 through Day 28 of Cycle 1

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite Pharmacokinetic (PK) Analysis
Time Frame: At days -14, 1,and 22 at 1, 2, 3, 6, and 24 hours after drug treatment and day -7 and prior to dosing on day -4
PKs derived from serum concentrations versus time for RAD001 on day -14, 1, and 22 at 1, 2, 3, 6, and 24 hours after drug administration as well as day -7 (h 168) and prior to dosing on Day 4.
At days -14, 1,and 22 at 1, 2, 3, 6, and 24 hours after drug treatment and day -7 and prior to dosing on day -4
Preliminary clinical evidence of anti-tumor activity by time to progression and RECIST criteria with this regimen
Time Frame: Baseline and every 2 courses (8 weeks)
Baseline and every 2 courses (8 weeks)
Association between clinical outcomes and biologic markers that may predict sensitivity of a tumor in patients treated with this regimen
Time Frame: Baseline, 24 hours post-treatment on day 22
Baseline, 24 hours post-treatment on day 22
Pharmacodynamic effects of this regimen on post-therapy tumor and/or skin specimens
Time Frame: At baseline, 24 hours post-therapy on day 22
At baseline, 24 hours post-therapy on day 22

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fox Chase Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Barbara Burtness, Fox Chase Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2008

Primary Completion (ACTUAL)

July 1, 2011

Study Completion (ACTUAL)

July 1, 2011

Study Registration Dates

First Submitted

October 20, 2011

First Submitted That Met QC Criteria

July 6, 2012

First Posted (ESTIMATE)

July 11, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

July 11, 2012

Last Update Submitted That Met QC Criteria

July 6, 2012

Last Verified

July 1, 2012

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB 06-043
  • NCI-2011-02971 (REGISTRY: CTRP (Clinical Trial Reporting Program))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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