Chemotherapy & Erlotinib in Treating Patients w/ Esophageal or Gastroesophageal Cancer That Cannot Be Removed by Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00539617
Recruitment Status : Terminated (For slow accrual)
First Posted : October 4, 2007
Results First Posted : October 12, 2012
Last Update Posted : October 12, 2012
Genentech, Inc.
Information provided by (Responsible Party):
University of California, San Francisco

Brief Summary:
The purpose of this study is to test the safety and effectiveness of erlotinib and FOLFOX in patients with esophageal or gastro-esophageal cancer that cannot be removed by surgery.

Condition or disease Intervention/treatment Phase
Esophageal Cancer Drug: erlotinib Drug: 5-fluorouracil Drug: leucovorin Drug: oxaliplatin Phase 2

Detailed Description:
More than 50% of patients with advanced esophageal cancer present with disease that cannot be removed by surgery or has spread to other parts of the body. Improved therapies for patients with advanced esophageal cancer are therefore urgently needed. The epidermal growth factor receptor (EGFR) inhibitor erlotinib (in combination with chemotherapy) has lead to improved survival in patients with pancreatic and lung cancer. EGFR is a target in esophageal cancer therapy since its overexpression is associated with more aggressive disease and poor survival. Early studies have shown some clinical activity of EGFR inhibitors in this disease alone or in combination with chemotherapy. This study aims to explore how safe and effective treatment with erlotinib and FOLFOX is in patients with advanced esophageal or gastro-esophageal cancer.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single-Arm, Phase II Study of Tarceva Plus FOLFOX6 in Patients With Unresectable or Metastatic Cancer of Esophagus or Gastroesophageal Junction
Study Start Date : October 2007
Actual Primary Completion Date : May 2011
Actual Study Completion Date : May 2011

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Tarceva and FOLFOX Drug: erlotinib
Tarceva single agent therapy: 150 mg/day PO
Other Name: tarceva
Drug: 5-fluorouracil
5-FU bolus: 400 mg/m2 IV once every 2 weeks for 16 weeks 5-FU infusion: 2400 mg/m2 IV over 46-48 hours, once every 2 weeks for 16 weeks
Drug: leucovorin
400 mg/m2 IV once every 2 weeks for 16 weeks
Drug: oxaliplatin
85 mg/m2 IV once every 2 weeks for 16 weeks

Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: 2 years ]
    To determine the number of participants with progression free survival after 6 months form the first day of the Erlotinib Run-In Phase for patients treated on study.

Secondary Outcome Measures :
  1. Response Rate (RR) [ Time Frame: 2 years ]
    To determine the number of participants with partial response (PR) or stable disease (SD) for the objective tumor response rate in the selected patient population treated with erlotinib and FOLFOX.

  2. To Determine the Time to Progression in This Population After Initiation of Erlotinib Alone, Following Erlotinib and FOLFOX Combination Chemotherapy. [ Time Frame: 2 years ]
  3. To Determine Toxicity and Tolerability of the Erlotinib and FOLFOX Treatment Regimen in the Selected Patient Population. [ Time Frame: 2 years ]
  4. To Estimate the Correlation of Epidermal Growth Factor Receptor (EGFR) Gene Amplification and EGFR Gene Expression Levels in Esophageal Cancer. [ Time Frame: 2 years ]
  5. To Determine the Effects of Erlotinib on EGFR Signaling and Tumor Cell Survival in Esophageal Cancer. [ Time Frame: 2 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically confirmed esophageal carcinoma (squamous or adenocarcinoma).
  • Surgically unresectable disease and/or metastatic disease. Endoscopic accessibility of primary tumor preferred but not a prerequisite.
  • No prior chemotherapy therapy except for neoadjuvant treatment (radiation and/or chemotherapy). Prior treatment with EGFR-inhibiting agents NOT allowed.
  • Life expectancy >12 weeks.
  • Ability to take and retain oral medications, or have an appropriate percutaneous feeding tube in place.
  • ECOG performance status of 0, 1, or 2 (Karnofsky Performance Status [KPS] ≥50%).
  • Measurable disease by RECIST criteria and computerized tomographic scan performed within 28 days prior to registration.
  • Organ system function assessed within 7 days prior to registration and within the following parameters:
  • Absolute neutrophil count ≥ 1500/mL;
  • Platelet count ≥ 100,000/mL;
  • Hemoglobin level ≥ 10.0 gm/dL;
  • Serum creatinine ≤ 1.5 x IULN (Institutional Upper Limits of Normal); OR Measured creatinine clearance ≥ 60 mL/min;
  • AST (SGOT) or ALT (SGPT) ≤ 2.5 x IULN (unless the liver is involved by tumor, in which case it must be ≤ 5.0 x IULN);
  • Total bilirubin ≤ 1.5 x IULN.
  • Aged 18 years or older
  • Provision of written informed consent
  • Women of childbearing potential (WOCBP) must be willing to practice acceptable methods of birth control to prevent pregnancy. WOCBP are any females who have experienced menarche and who have not undergone surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), who are not postmenopausal (defined as amenorrhea greater than or equal to 12 consecutive months), or are on hormone replacement therapy. Acceptable methods of birth control include oral or hormonal contraceptives and barrier methods (e.g., condom, diaphragm) used in combination with other methods (e.g., spermicide).
  • Male patients who are capable of fathering a child must avoid doing so while participating in this study through the use of acceptable methods of birth control. This is a precautionary measure because this study involves chemotherapy agents.

Exclusion Criteria:

  • Presence of a Kras mutation.
  • Lack of expression of EGFR.
  • Prior treatment with EGFR-inhibiting agents, chemotherapy, or radiotherapy for esophagogastric carcinomas (other than neoadjuvant treatment as noted in inclusion criteria).
  • Patients must not be receiving any other investigational agents. Use of erythropoietin is allowable. Secondary prophylaxis with granulocyte colony stimulating factor (G-CSF) (Filgrastim) is allowable.
  • Concomitant use of phenytoin, carbamazepine, barbiturates, rifampicin, phenobarbital, or St. John's wort.
  • Uncontrolled brain metastases.
  • Patients must not have uncontrolled intercurrent illness at the time of registration 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.
  • Patients must not have current New York Heart Association Class III or IV heart disease.
  • Known human immunodeficiency virus (HIV) infection.
  • Pregnant or breast-feeding women.
  • Patients who have had prior malignancies, except non-melanoma skin cancer (basal or squamous cell carcinoma) are not eligible for this study; unless greater than 5 years has passed since the event.
  • Known severe hypersensitivity to Tarceva.
  • Treatment with a non-approved or investigational drug within 30 days before Day 1 of trial treatment.
  • Incomplete healing from previous oncologic or other major surgery.
  • Serum creatinine level greater than Common Toxicity Criteria (CTC) grade 2.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00539617

United States, California
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94115
Sponsors and Collaborators
University of California, San Francisco
Genentech, Inc.
Principal Investigator: W. Michael Korn, MD University of California, San Francisco

Responsible Party: University of California, San Francisco Identifier: NCT00539617     History of Changes
Other Study ID Numbers: CC#064511
First Posted: October 4, 2007    Key Record Dates
Results First Posted: October 12, 2012
Last Update Posted: October 12, 2012
Last Verified: September 2012

Keywords provided by University of California, San Francisco:
metastatic esophageal cancer
advanced esophageal cancer
unresectable esophageal cancer

Additional relevant MeSH terms:
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Erlotinib Hydrochloride
Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors