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

This study has been terminated.
(low enrollment)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00290719
First received: February 9, 2006
Last updated: May 7, 2014
Last verified: May 2014
  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
Radiation: radiation therapy
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

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 ]

Enrollment: 6
Study Start Date: November 2005
Study Completion Date: June 2008
Primary Completion Date: April 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
University of California, San Francisco
Investigators
Study Chair: Andrew Ko, MD University of California, San Francisco
  More Information

No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00290719     History of Changes
Other Study ID Numbers: CDR0000456200, UCSF-034510, ZENECA-1839US/0244
Study First Received: February 9, 2006
Last Updated: May 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, San Francisco:
adenocarcinoma of the esophagus
squamous cell carcinoma of the esophagus
stage II esophageal cancer
stage III esophageal cancer

Additional relevant MeSH terms:
Esophageal Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Esophageal Diseases
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Head and Neck Neoplasms
Neoplasms
Neoplasms by Site
Cisplatin
Gefitinib
Irinotecan
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 30, 2014