Cetuximab and Everolimus in Treating Patients With Metastatic or Recurrent Colon Cancer or Head and Neck Cancer
A Phase I Evaluation of Cetuximab and RAD001 in Patients With Solid Tumors
2 other identifiers
interventional
12
1 country
1
Brief Summary
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Nov 2008
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 1, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2011
CompletedFirst Submitted
Initial submission to the registry
October 20, 2011
CompletedFirst Posted
Study publicly available on registry
July 11, 2012
CompletedJuly 11, 2012
July 1, 2012
2.7 years
October 20, 2011
July 6, 2012
Conditions
Outcome Measures
Primary Outcomes (1)
Number of patients with dose limiting toxicity
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 Outcomes (4)
Composite Pharmacokinetic (PK) Analysis
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
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
Baseline, 24 hours post-treatment on day 22
Pharmacodynamic effects of this regimen on post-therapy tumor and/or skin specimens
At baseline, 24 hours post-therapy on day 22
Study Arms (1)
Treatment (enzyme inhibitor, monoclonal antibody therapy)
EXPERIMENTALPatients 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.
Interventions
Given PO
Given IV
Correlative studies
Correlative studies
Eligibility Criteria
You may qualify if:
- 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
- +3 more criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Fox Chase Cancer Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111-2497, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Barbara Burtness
Fox Chase Cancer Center
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
October 20, 2011
First Posted
July 11, 2012
Study Start
November 1, 2008
Primary Completion
July 1, 2011
Study Completion
July 1, 2011
Last Updated
July 11, 2012
Record last verified: 2012-07