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

Sponsors and Collaborators:	UCSF Helen Diller Family Comprehensive Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00290719

Purpose

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.

Condition	Intervention	Phase
Esophageal Cancer	Drug: cisplatin Drug: gefitinib Drug: irinotecan hydrochloride Procedure: conventional surgery Procedure: neoadjuvant therapy Procedure: radiation therapy	Phase I Phase II

MedlinePlus related topics: Cancer Esophageal Cancer Esophagus Disorders

Drug Information available for: Cisplatin Irinotecan Irinotecan hydrochloride ZD1839

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Phase I/II Study to Evaluate Safety and Efficacy in Patients Who Have Resectable Esophageal Cancer and Are Treated With Neoadjuvant Cisplatin, Irinotecan (CPT-11) ZD1839 (IRESSA), and Radiotherapy Followed by Surgical Resection

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Pathological response (complete and partial) post-operatively [ Designated as safety issue: No ]

Secondary Outcome Measures:

Safety and toxicity post-operatively [ Designated as safety issue: Yes ]
Response rate 2 weeks into treatment, pre-operatively, and post-operatively [ Designated as safety issue: No ]
Completeness of resection post-operatively [ Designated as safety issue: No ]
Surgical morbidity and mortality post-operatively [ Designated as safety issue: No ]
Compare the effects of gefitinib on biomarkers that effect EGF signaling and genomic composition of tumor samples before and after treatment [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	November 2005
Estimated Primary Completion Date:	March 2008 (Final data collection date for primary outcome measure)

Detailed 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00290719

Locations

United States, California
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115

Sponsors and Collaborators

UCSF Helen Diller Family Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Andrew Ko, MD

UCSF Helen Diller Family Comprehensive Cancer Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Responsible Party:	UCSF Helen Diller Family Comprehensive Cancer Center ( Andrew Ko )
Study ID Numbers:	CDR0000456200, UCSF-034510, ZENECA-1839US/0244
Study First Received:	February 9, 2006
Last Updated:	October 23, 2008
ClinicalTrials.gov Identifier:	NCT00290719
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

adenocarcinoma of the esophagus
squamous cell carcinoma of the esophagus
stage II esophageal cancer
stage III esophageal cancer

Study placed in the following topic categories:

Digestive System Neoplasms
Esophageal disorder
Gastrointestinal Diseases
Esophageal Neoplasms
Squamous cell carcinoma
Irinotecan
Camptothecin
Carcinoma
Epidermoid carcinoma
Digestive System Diseases

Cisplatin
Head and Neck Neoplasms
Carcinoma, squamous cell
Gastrointestinal Neoplasms
Esophageal Diseases
Carcinoma, Squamous Cell
Adenocarcinoma
Gefitinib
Esophageal neoplasm

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site
Molecular Mechanisms of Pharmacological Action
Radiation-Sensitizing Agents
Antineoplastic Agents
Therapeutic Uses

Physiological Effects of Drugs
Enzyme Inhibitors
Protein Kinase Inhibitors
Antineoplastic Agents, Phytogenic
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009