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Adenocarcinoma of the ColonPhase 1NCT00397384

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 1 study testing cetuximab, erlotinib hydrochloride and laboratory biomarker analysis in people with Adenocarcinoma of the Colon and Adenocarcinoma of the Rectum, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
cetuximab, erlotinib hydrochloride and laboratory biomarker analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
1 siteUnited States
Study dates
Jan 2007to Jun 2013
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232

Other trials in United States

About this study

Official title: A Phase I Clinical and Biological Evaluation of Combined EGFR Blockade With Erlotinib and Cetuximab in Patients With Advanced Cancer

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To identify the maximum tolerated dose (MTD). II. To identify the recommended dose (RD) for phase II of erlotinib (erlotinib hydrochloride) in combination with cetuximab in patients (pts) with incurable gastrointestinal, head and neck, or non-small cell lung cancers that are Kirsten rat sarcoma viral oncogene homolog (KRAS) wild type.

SECONDARY OBJECTIVES:

  1. To identify dose-limiting toxicities (DLT). II. To perform skin and tumor biopsies to analyze molecular inhibition of the epidermal growth factor receptor (EGFR) signaling pathway, defined as a >= 75% inhibition of phosphorylation of the epidermal growth factor (EGF) receptor or of its downstream effectors tumor protein (p)44/42 mitogen-activated protein kinase (MAPK) or protein kinase B (Akt) or as a >= 25% decrease of marker of proliferation Ki-67 (Ki67) from baseline in either skin or tumor tissue in the majority of patients.

III. To identify the optimal biological dose (OBD). IV. To describe any antitumor effect observed.

OUTLINE: This is a phase I, dose-escalation study of erlotinib hydrochloride.

Patients receive cetuximab intravenously (IV) over 1-2 hours on days 1, 8, and 15 and erlotinib hydrochloride orally (PO) once daily (QD) on days 8-21. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 4 weeks.

Being tested
cetuximab, erlotinib hydrochloride, laboratory biomarker analysis
Medical subject headings
Colonic Neoplasms, Rectal Neoplasms, Appendiceal Neoplasms, Gastrointestinal Stromal Tumors, Carcinoma, Hepatocellular, Anus Neoplasms, Esophageal Neoplasms, Esthesioneuroblastoma, Olfactory

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • cetuximabDrug

    Also called C225, C225 monoclonal antibody, IMC-C225, MOAB C225

    Given IV

  • erlotinib hydrochlorideDrug

    Also called CP-358,774, erlotinib, OSI-774

    Given PO

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00397384
Study groupRoleWhat they receive
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.
Receives: Drug: cetuximab; Drug: erlotinib hydrochloride; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

    Measured: 21 days

  2. MTD defined as the dose level at which fewer than 2 out of 6 patients experience DLT graded using CTCAE-v3

    Measured: 21 days

Secondary outcomes (3)

  1. Change in molecular inhibition of the EGFR signaling pathway

    These data will be descriptive in nature, with no hypothesis testing. Summary statistics including numbers of subjects that met response criteria, and mean, median and standard deviation in the percent staining, all by dose level.

    Measured: Baseline to up to 4 weeks

  2. 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%

    These data will be descriptive in nature, with no hypothesis testing. Summary statistics including numbers of subjects that met response criteria, and mean, median and standard deviation in the percent staining, all by dose level.

    Measured: Up to 4 weeks

  3. Antitumor effect observed

    Measured: Up to 4 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Nov 2006 (estimated)
  2. Study startJan 2007
  3. Primary completionJun 2013
  4. Study completionJun 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00397384
Sponsor's protocol ID
NCI-2009-00107
Other IDs
NCI-2009-00107, CDR0000511880, GI 0622, 6980, P30CA068485
Status last verified
Feb 2014
First submitted
8 Nov 2006
Last updated
30 Sep 2015
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing cetuximab, erlotinib hydrochloride and laboratory biomarker analysis in people with Adenocarcinoma of the Colon and Adenocarcinoma of the Rectum, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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) (time frame: 21 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00397384.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2015.

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