A Single-Arm, Phase II Study of Tarceva Plus FOLFOX6 in Patients With Unresectable or Metastatic Cancer of Esophagus or Gastroesophageal Junction
- 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
- 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.
- 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
- 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
- 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
- Incomplete healing from previous oncologic or other major surgery.
- Serum creatinine level greater than Common Toxicity Criteria (CTC) grade 2.