Gefitinib, Cisplatin, Irinotecan, and Radiation Therapy Before Surgery in Treating Patients With Esophageal Cancer or Gastroesophageal Junction Cancer That Can Be Removed By Surgery

University of California San Francisco (UCSF)

Status and phase

Terminated

Phase 1

Conditions

Esophageal Cancer

Treatments

Procedure: neoadjuvant therapy

Drug: irinotecan hydrochloride

Drug: gefitinib

Drug: cisplatin

Radiation: radiation therapy

Procedure: conventional surgery

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00290719

UCSF-034510

CDR0000456200

ZENECA-1839US/0244

Details and patient eligibility

About

RATIONALE: Gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin and irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving gefitinib together with chemotherapy and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase I/II trial is studying the side effects of gefitinib when given together with cisplatin, irinotecan, and radiation therapy before surgery and to see how well they work in treating patients with esophageal cancer or gastroesophageal junction cancer that can be removed by surgery.

Full description

OBJECTIVES:

Primary

Evaluate the pathologic response (complete and partial) in patients with resectable esophageal or gastroesophageal junction cancer treated with neoadjuvant gefitinib, cisplatin, irinotecan hydrochloride, and radiotherapy followed by surgical resection.

Secondary

Assess the safety and toxicity of this regimen in these patients.
Evaluate objective tumor response in patients treated with this regimen.
Determine the rate of complete resection in patients treated with this regimen.
Determine surgical morbidity and mortality in patients treated with this regimen.

OUTLINE: This is an open-label study.

Induction phase: Patients receive oral gefitinib once daily on days 1-14. Patients with stable or responding disease proceed to neoadjuvant chemoradiotherapy.
Neoadjuvant chemoradiotherapy: Patients receive gefitinib as in the induction phase beginning in week 4 and continuing through the last day of radiotherapy. Patients also receive cisplatin IV over 1 hour and irinotecan hydrochloride IV over 30 minutes on days 22, 29, 43, and 50 and undergo radiotherapy once daily, 5 days a week, for 5 weeks (total of 25 doses).
Surgery: Within 4-8 weeks after completion of neoadjuvant chemoradiotherapy, patients with stable or responding disease undergo an esophagectomy and lymph node dissection. Patients with a progressive or unresectable disease are removed from the study.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Enrollment

6 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically confirmed adenocarcinoma (AC) or squamous cell carcinoma of the esophagus
- AC of the gastroesophageal junction allowed
Tumor must be considered surgically resectable (T1-3, NX)
- No early-stage cancer (T1, N0)
The following lymph node (LN) criteria are considered acceptable:
- Regional thoracic LN metastases (N1)
- LN metastases levels 15 to 20 measured as ≤ 1.5 cm by CT scan
- Supraclavicular LN not palpable on clinical examination measured as ≤ 1.5 cm by CT scan
No distant metastases (M0)

PATIENT CHARACTERISTICS:

Platelet count ≥ 100,000/mm^3
Absolute neutrophil count ≥ 1,500/mm^3
Hemoglobin ≥ 9.0 g/dL
Creatinine clearance ≥ 50 mL/min
Creatinine serum level ≤ CTC grade 2
Bilirubin ≤ 2 times upper limit of normal (ULN)
AST < 3 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 3 months after completion of study treatment
No known severe hypersensitivity to gefitinib or any of its excipients
No evidence (except asymptomatic chronic stable radiographic changes) of clinically active interstitial lung disease
No pulmonary fibrosis, Gilbert's disease, uncontrolled diabetes mellitus, or unstable angina
No New York Heart Association class III or IV heart disease
No other concurrent malignancies or malignancies diagnosed within the past 5 years except basal cell carcinoma or carcinoma in situ of the cervix
No serious active or uncontrolled infection, systemic disease, psychiatric illness, or other medical condition that would preclude study participation
No evidence of any significant clinical disorder or laboratory finding that would preclude study participation

PRIOR CONCURRENT THERAPY:

No prior chemotherapy or radiotherapy for esophageal cancer
No prior radiotherapy that would overlap the study treatment fields
Recovered from prior major surgery
No nonapproved or investigational drugs within the past 30 days
No concurrent phenytoin, carbamazepine, barbiturates, rifampin, phenobarbital, or Hypericum perforatum (St. John's wort)