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A Phase I/II Clinical and Biological Evaluation of Combined EGFR Blockade With Erlotinib and Cetuximab in Patients With Advanced Cancer (Phase I) or Advanced Colorectal Cancer (Phase II)


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Adenocarcinoma of the Colon, Adenocarcinoma of the Rectum, Advanced Adult Primary Liver Cancer, Carcinoma of the Appendix, Gastrointestinal Stromal Tumor, Metastatic Gastrointestinal Carcinoid Tumor, Metastatic Squamous Neck Cancer With Occult Primary, Recurrent Adenoid Cystic Carcinoma of the Oral Cavity, Recurrent Adult Primary Liver Cancer, Recurrent Anal Cancer, Recurrent Basal Cell Carcinoma of the Lip, Recurrent Colon Cancer, Recurrent Esophageal Cancer, Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Recurrent Extrahepatic Bile Duct Cancer, Recurrent Gallbladder Cancer, Recurrent Gastric Cancer, Recurrent Gastrointestinal Carcinoid Tumor, 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 Non-small Cell Lung Cancer, Recurrent Pancreatic Cancer, Recurrent Rectal Cancer, Recurrent Salivary Gland Cancer, Recurrent Small Intestine 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, Small Intestine Adenocarcinoma, Small Intestine Leiomyosarcoma, Small Intestine Lymphoma, Stage IV Adenoid Cystic Carcinoma of the Oral Cavity, Stage IV Anal Cancer, Stage IV Basal Cell Carcinoma of the Lip, Stage IV Colon Cancer, Stage IV Esophageal Cancer, Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Stage IV Gastric Cancer, Stage IV Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Stage IV Lymphoepithelioma of the Nasopharynx, Stage IV Lymphoepithelioma of the Oropharynx, Stage IV Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Stage IV Mucoepidermoid Carcinoma of the Oral Cavity, Stage IV Non-small Cell Lung Cancer, Stage IV Pancreatic Cancer, Stage IV Rectal Cancer, Stage IV Salivary Gland Cancer, 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 Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IV Verrucous Carcinoma of the Larynx, Stage IV Verrucous Carcinoma of the Oral Cavity, Tongue Cancer, Unresectable Extrahepatic Bile Duct Cancer, Unresectable Gallbladder Cancer

Thank you

Trial Information

A Phase I/II Clinical and Biological Evaluation of Combined EGFR Blockade With Erlotinib and Cetuximab in Patients With Advanced Cancer (Phase I) or Advanced Colorectal Cancer (Phase II)


PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of erlotinib hydrochloride when administered with
cetuximab in patients with advanced gastrointestinal, head and neck, or non-small cell lung
cancer. (Phase I) II. Determine the recommended phase II dose of this regimen in these
patients. (Phase I) III. Determine the response rate in patients with refractory advanced
colorectal cancer treated with this regimen. (Phase II)

SECONDARY OBJECTIVES:

I. Determine the dose-limiting toxicity of this regimen in these patients. (Phase I) II.
Determine the optimal biological dose of this regimen in these patients. (Phase I) III.
Describe any antitumor effect of this regimen in these patients. (Phase I) IV. Determine the
4-month progression-free survival rate in patients treated with this regimen. (Phase II) V.
Determine the time to tumor progression in patients treated with this regimen. (Phase II)
VI. Determine the median survival of patients treated with this regimen. (Phase II) VII.
Determine safety and tolerability of this regimen in these patients. (Phase II)

OUTLINE: This is a phase I, nonrandomized, dose-escalation study of erlotinib hydrochloride
followed by a phase II, open-label study.

PHASE I: Patients receive cetuximab IV over 1-2 hours on days 1, 8, and 15 and oral
erlotinib hydrochloride once daily on days 8-21. Treatment repeats every 21 days in the
absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 2 of 6 patients experience dose-limiting toxicity.

PHASE II: Patients receive cetuximab and erlotinib hydrochloride as in phase I at the MTD.

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


Inclusion Criteria:



- Histologically or cytologically confirmed diagnosis of 1 of the following:

- Gastrointestinal cancer

- Head and neck cancer

- Non-small cell lung cancer

- Colorectal adenocarcinoma meeting the following criteria:

- Unresectable disease

- Evidence of new or progressive metastatic lesions within the past 6 months

- At least 1 metastatic tumor site must be accessible for biopsy

- KRAS wild type by PCR assay or directed sequencing of KRAS exon and codons 12 and 13.
May undergo a needle or excisional biopsy of a malignant site prior to enrollment if
KRAS mutational status cannot be determined on archived tumor tissue.

- Incurable, advanced disease

- WBC >= 3,000/mm³

- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%

- Received >= 1 prior systemic regimen for advanced/metastatic disease, including
fluorouracil and leucovorin calcium and either oxaliplatin or irinotecan
hydrochloride (Phase II). Any type of prior antineoplastic therapy allowed, except
for epidermal growth factor receptor (EGFR) inhibitors.

- Measurable disease (Phase II), defined as >= 1 unidimensionally measurable lesion >=
20 mm by conventional techniques OR >= 10 mm by spiral CT scan. Target lesions may
not be in a previously irradiated field unless progression of the lesion has been
documented.

- History of brain metastases allowed provided >= 1 of the following criteria are met:

- Metastases have been surgically resected

- Radiographically and clinically stable for 2 months after completion of
radiotherapy

- Absolute neutrophil count >= 1,500/mm³

- Platelet count >= 100,000/mm³

- Bilirubin normal

- AST and ALT =< 2.5 times upper limit of normal

- Creatinine normal OR creatinine clearance >= 60 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for >= 60 days after
completion of study treatment

- Other prior malignancies allowed provided prior therapy has been discontinued and
there is no evidence of disease

- Able to take and retain oral medications

- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to erlotinib hydrochloride or cetuximab

- No significant traumatic injury within the past 21 days

- No abnormalities of the cornea based on history (e.g., dry eye syndrome or Sjögren's
syndrome), congenital abnormality (e.g., Fuch's dystrophy), abnormal slit-lamp
examination using a vital dye (e.g., fluorescein or Bengal-Rose), and/or an abnormal
corneal sensitivity test (Schirmer test or similar tear production test)

- No gastrointestinal tract disease resulting in an inability to take oral medication

- No requirement for IV alimentation

- No active peptic ulcer disease

- No uncontrolled intercurrent illness, including, but not limited to, any of the
following:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness or social situation that would preclude study compliance

- At least 4 weeks since prior biologic therapy, chemotherapy, or radiotherapy (6 weeks
for nitrosoureas or mitomycin C) and recovered

- No prior EGFR-targeting therapies

- No prior surgical procedures affecting absorption

- At least 21 days since prior major surgery or biopsy of a parenchymal organ

- No concurrent CYP3A4-inducing agents

- No other concurrent investigational agents

- No other concurrent anticancer agents or therapies

- No concurrent combination antiretroviral therapy for HIV-positive patients

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Maximum tolerated dose and recommended phase II dose defined by dose limiting toxicities of erlotinib hydrochloride when administered with cetuximab (phase I)

Outcome Time Frame:

21 days

Safety Issue:

No

Principal Investigator

Laura Goff

Investigator Role:

Principal Investigator

Investigator Affiliation:

Vanderbilt University

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00107

NCT ID:

NCT00397384

Start Date:

January 2007

Completion Date:

Related Keywords:

  • Adenocarcinoma of the Colon
  • Adenocarcinoma of the Rectum
  • Advanced Adult Primary Liver Cancer
  • Carcinoma of the Appendix
  • Gastrointestinal Stromal Tumor
  • Metastatic Gastrointestinal Carcinoid Tumor
  • Metastatic Squamous Neck Cancer With Occult Primary
  • Recurrent Adenoid Cystic Carcinoma of the Oral Cavity
  • Recurrent Adult Primary Liver Cancer
  • Recurrent Anal Cancer
  • Recurrent Basal Cell Carcinoma of the Lip
  • Recurrent Colon Cancer
  • Recurrent Esophageal Cancer
  • Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
  • Recurrent Extrahepatic Bile Duct Cancer
  • Recurrent Gallbladder Cancer
  • Recurrent Gastric Cancer
  • Recurrent Gastrointestinal Carcinoid Tumor
  • 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 Non-Small Cell Lung Cancer
  • Recurrent Pancreatic Cancer
  • Recurrent Rectal Cancer
  • Recurrent Salivary Gland Cancer
  • Recurrent Small Intestine 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
  • Small Intestine Adenocarcinoma
  • Small Intestine Leiomyosarcoma
  • Small Intestine Lymphoma
  • Stage IV Adenoid Cystic Carcinoma of the Oral Cavity
  • Stage IV Anal Cancer
  • Stage IV Basal Cell Carcinoma of the Lip
  • Stage IV Colon Cancer
  • Stage IV Esophageal Cancer
  • Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
  • Stage IV Gastric Cancer
  • Stage IV Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
  • Stage IV Lymphoepithelioma of the Nasopharynx
  • Stage IV Lymphoepithelioma of the Oropharynx
  • Stage IV Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
  • Stage IV Mucoepidermoid Carcinoma of the Oral Cavity
  • Stage IV Non-Small Cell Lung Cancer
  • Stage IV Pancreatic Cancer
  • Stage IV Rectal Cancer
  • Stage IV Salivary Gland Cancer
  • 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 Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Stage IV Verrucous Carcinoma of the Larynx
  • Stage IV Verrucous Carcinoma of the Oral Cavity
  • Tongue Cancer
  • Unresectable Extrahepatic Bile Duct Cancer
  • Unresectable Gallbladder Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Anus Neoplasms
  • Carcinoid Tumor
  • Carcinoma
  • Colonic Neoplasms
  • Rectal Neoplasms
  • Carcinoma, Basal Cell
  • Carcinoma, Non-Small-Cell Lung
  • Carcinoma, Squamous Cell
  • Colorectal Neoplasms
  • Carcinoma, Adenoid Cystic
  • Esophageal Diseases
  • Esophageal Neoplasms
  • Granuloma
  • Head and Neck Neoplasms
  • Laryngeal Diseases
  • Leiomyosarcoma
  • Liver Neoplasms
  • Lung Neoplasms
  • Lymphoma
  • Stomach Neoplasms
  • Pancreatic Neoplasms
  • Papilloma
  • Tongue Neoplasms
  • Duodenal Neoplasms
  • Ileal Neoplasms
  • Jejunal Neoplasms
  • Gallbladder Neoplasms
  • Bile Duct Neoplasms
  • Carcinoma, Mucoepidermoid
  • Carcinoma, Verrucous
  • Esthesioneuroblastoma, Olfactory
  • Papilloma, Inverted
  • Malignant Carcinoid Syndrome
  • Gastrointestinal Neoplasms
  • Neoplasms, Unknown Primary
  • Salivary Gland Neoplasms
  • Gastrointestinal Stromal Tumors
  • Hypopharyngeal Neoplasms
  • Laryngeal Neoplasms
  • Intestinal Neoplasms
  • Paranasal Sinus Neoplasms
  • Oropharyngeal Neoplasms
  • Nasopharyngeal Neoplasms

Name

Location

Vanderbilt UniversityNashville, Tennessee  37232-6305