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A Phase I Study of Preoperative Chemoradiation With Oxaliplatin, 5-Fluorouracil, Erlotinib and Radiation Followed by Resection and Consolidative Erlotinib for Patients With Locally Advanced Cancer of the Esophagus and Gastroesophageal Junction

Phase 1
18 Years
Open (Enrolling)
Adenocarcinoma of the Esophagus, Adenocarcinoma of the Gastroesophageal Junction, Adenocarcinoma of the Stomach, Squamous Cell Carcinoma of the Esophagus, Stage II Esophageal Cancer, Stage II Gastric Cancer, Stage III Esophageal Cancer, Stage III Gastric Cancer

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Trial Information

A Phase I Study of Preoperative Chemoradiation With Oxaliplatin, 5-Fluorouracil, Erlotinib and Radiation Followed by Resection and Consolidative Erlotinib for Patients With Locally Advanced Cancer of the Esophagus and Gastroesophageal Junction


I. The primary aim of this phase I study is to evaluate the safety of multi-drug
chemotherapy (with the addition of an anti-epidermal growth factor receptor [EGFR] agent
erlotinib [erlotinib hydrochloride]) and concomitant radiotherapy followed by resection and
consolidative erlotinib for the treatment of locally advanced esophageal cancer as judged by
the dose limiting toxicities. Correlative endpoints include an analysis of pre-treatment
tumor cyclin D1 expression and EGFR expression/amplification.

III. Correlate pathologic complete response with changes in fludeoxyglucose F 18
(FDG)-positron emission tomography (PET)-computed tomography (CT) - pre and

OUTLINE: This is a dose escalation study of erlotinib hydrochloride

CHEMORADIOTHERAPY: Patients undergo radiation therapy once daily (QD), 5 days a week and
receive fluorouracil intravenously (IV) continuously and erlotinib hydrochloride orally (PO)
QD on days 1-38. Patients also receive oxaliplatin IV over 2 hours on days 1, 15, and 29.

SURGERY: Within 4-8 weeks after completion of chemoradiotherapy, patients with potentially
resectable disease (i.e., complete response, partial response, or stable disease) undergo
surgery to remove the tumor.

CONSOLIDATION CHEMOTHERAPY: Within 2-4 weeks after surgery, patients with tumors that
demonstrate positive immunohistochemistry for EGFR and/or cyclin D1 (in the pretreatment
biopsy or in the residual tumor in the esophagectomy specimen) receive consolidation
chemotherapy comprising erlotinib hydrochloride PO QD for 12 weeks.

After completion of study treatment, patients are followed every 3 months for 2 years, every
6 months for 2 years, and then annually thereafter.

Inclusion Criteria:

- Newly diagnosed patients with locally advanced esophageal cancer with either squamous
or adenocarcinoma histology; patients should have evidence of extension of disease
into or through the wall of the esophagus (T2-4) and/or regional nodal metastasis

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Non-pregnant; patients of childbearing potential and their partners must agree to use
an effective form of contraception during the study and for 90 days following the
last dose of study medication (an effective form of contraception is an oral
contraceptive or a double barrier method); nursing mothers are also ineligible

- Prior treatment: Greater than one week shall have elapsed since any major surgery; no
prior chemotherapy or radiotherapy is allowed

- Adequate whole blood cell (WBC) and platelets (Plt) as determined by medical oncology

- Serum creatinine =< 1.5 mg/dl

- Creatinine clearance >= 60 ml/min

- Hemoglobin (Hgb) >= 9.0 gm/dl

- Absolute neutrophil count >= 1,500/uL

- Serum total bilirubin =< 1.5 mg/dL

- Alkaline phosphatase =< 3X the upper limit of normal (ULN) for the reference lab

- Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than 2X ULN for
the reference laboratory

- Patients must be told of the investigational nature of the study and must sign a
written informed consent

- No serious medical or psychiatric illnesses which would prevent informed consent or
otherwise limit survival to less than two years; no history of refractory congestive
heart failure or cardiomyopathy

- Patients should be evaluated by medical oncology, radiation oncology, and surgery,
and felt to by all to be suitable for trimodality therapy

Exclusion Criteria:

Patients with an active infection or with a fever >= 38.5 degrees Celsius (C) within 3
days of the first scheduled day of protocol treatment

- History of prior malignancy within the past 5 years except for curatively treated
basal cell carcinoma of the skin, cervical intra-epithelial neoplasia, or localized
prostate cancer with a current prostate surface antigen (PSA) of < 1.0 mg/dL on 2
successive evaluations, at least 3 months apart, with the most recent evaluation no
more than 4 weeks prior to entry

- Patients with known hypersensitivity to any of the components of oxaliplatin

- Patients who are receiving concurrent investigational therapy or who have received
investigational therapy within 30 days of the first scheduled day of protocol
treatment (investigational therapy is defined as treatment for which there is
currently no regulatory authority approved indication)

- Peripheral neuropathy >= Grade 2

- History of allogeneic transplant

- Known human immunodeficiency virus (HIV) or Hepatitis B or C (active, previously
treated or both)

- Pregnancy

Type of Study:


Study Design:

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

Outcome Measure:

Toxicity rate of combination chemotherapy followed by surgery and erlotinib hydrochloride

Outcome Description:

Toxicity will be determined using the revised National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 3.0 for Toxicity and Adverse Event Reporting (CTCAE v3.0). The dose limiting toxicity will be defined as any of the following that can be attributal to therapy: Any grade 4 neutropenia and or any grade 4 thrombocytopenia, or any >= grade 3 non-hematologic toxicity that results in a greater than 3 day interruption of therapy.

Outcome Time Frame:

Approximately 6 months

Safety Issue:


Principal Investigator

Arthur Blackstock

Investigator Role:

Principal Investigator

Investigator Affiliation:

Wake Forest University


United States: Institutional Review Board

Study ID:

CCCWFU 60106



Start Date:

April 2007

Completion Date:

Related Keywords:

  • Adenocarcinoma of the Esophagus
  • Adenocarcinoma of the Gastroesophageal Junction
  • Adenocarcinoma of the Stomach
  • Squamous Cell Carcinoma of the Esophagus
  • Stage II Esophageal Cancer
  • Stage II Gastric Cancer
  • Stage III Esophageal Cancer
  • Stage III Gastric Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Esophageal Diseases
  • Esophageal Neoplasms
  • Stomach Neoplasms



Wake Forest University Health SciencesWinston-Salem, North Carolina  27157