Erlotinib Hydrochloride and Cetuximab in Treating Patients With Advanced Gastrointestinal Cancer, Head and Neck Cancer, Non-Small Cell Lung Cancer, or Colorectal Cancer
A Phase I Clinical and Biological Evaluation of Combined EGFR Blockade With Erlotinib and Cetuximab in Patients With Advanced Cancer
5 other identifiers
interventional
43
1 country
1
Brief Summary
This phase I trial is studying the side effects and best dose of erlotinib hydrochloride when given together with cetuximab and to see how well they work in treating patients with advanced gastrointestinal cancer, head and neck cancer, non-small cell lung cancer, or colorectal cancer. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Erlotinib hydrochloride and cetuximab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving erlotinib hydrochloride together with cetuximab may kill more tumor cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jan 2007
Longer than P75 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
First Submitted
Initial submission to the registry
November 8, 2006
CompletedFirst Posted
Study publicly available on registry
November 9, 2006
CompletedStudy Start
First participant enrolled
January 1, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2013
CompletedSeptember 30, 2015
February 1, 2014
6.4 years
November 8, 2006
September 28, 2015
Conditions
Outcome Measures
Primary Outcomes (2)
Incidence of DLT, defined as recurring grade 2 or greater non-hematological or grade 3 or greater hematological toxicities or skin rash graded using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE-v3)
21 days
MTD defined as the dose level at which fewer than 2 out of 6 patients experience DLT graded using CTCAE-v3
21 days
Secondary Outcomes (3)
Change in molecular inhibition of the EGFR signaling pathway
Baseline to up to 4 weeks
OBD defined as the dose at which either a >= 75% inhibition of phosphorylation of the EGF receptor or of its downstream effectors p44/42 MAPK or Akt is observed, or Ki67 is decreased by >= 25%
Up to 4 weeks
Antitumor effect observed
Up to 4 weeks
Study Arms (1)
Treatment (cetuximab and erlotinib hydrochloride)
EXPERIMENTALPatients receive cetuximab IV over 1-2 hours on days 1, 8, and 15 and erlotinib hydrochloride PO QD on days 8-21. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Given PO
Correlative studies
Eligibility Criteria
You may qualify if:
- Patients must have histologically or cytologically confirmed incurable gastrointestinal tract, head and neck, or non-small cell lung cancers that are KRAS wild type; if KRAS mutational status cannot be determined on archived tumor tissue from the patient, a needle or excisional biopsy of a malignant site may be performed prior to enrollment; mutational status may be determined either by polymerase chain reaction (PCR) assay (e.g., DxS KRAS mutation kit) or by direct sequencing of KRAS exon 2, codons 12 and 13; the result must detect no mutations at these sites
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
- Leukocytes \>= 3,000/mcL
- Absolute neutrophil count \>= 1,500/mcL
- Platelets \>= 100,000/mcL
- Total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X institutional upper limit of normal
- Creatinine within normal institutional limits or creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
- Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of erlotinib will be determined following review of their case by the principal investigator; although concomitant use of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers is not prohibited in this study, identification of MTD and DLT may be affected by their use; concomitant use of any of these drugs will be noted in the case report forms and will be taken into account in determining MTD and DLT of this therapy; efforts should be made to switch patients with a history of brain metastases who are taking enzyme-inducing anticonvulsant agents to other medications
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Other prior malignancies are allowed provided prior therapy has been discontinued and there is no evidence of disease (NED)
- Patients must be able to take and retain oral medications
- Ability to understand and the willingness to sign a written informed consent document
You may not qualify if:
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients may not be receiving any other investigational agents
- Patients with a history of brain metastases are eligible provided that the metastases have been surgically resected and/or are radiographically and clinically stable for 2 months following the completion of radiation therapy
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to cetuximab
- Prior treatment with EGFR-targeting therapies
- Major surgery or significant traumatic injury occurring within 21 days prior to treatment
- Abnormalities of the cornea based on history (e.g., dry eye syndrome, Sjogren's syndrome), congenital abnormality (e.g., Fuch's dystrophy), abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal-Rose), and/or an abnormal corneal sensitivity test (Schirmer test or similar tear production test)
- Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with erlotinib or cetuximab
- Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Laura Goff
Vanderbilt-Ingram Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 8, 2006
First Posted
November 9, 2006
Study Start
January 1, 2007
Primary Completion
June 1, 2013
Study Completion
June 1, 2013
Last Updated
September 30, 2015
Record last verified: 2014-02