Cisplatin, Fluorouracil, Iressa, and Radiation Therapy Patients With Locally Advanced Head and Neck Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
David Adelstein, Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00352105
First received: July 13, 2006
Last updated: November 1, 2012
Last verified: November 2012
  Purpose

RATIONALE: Drugs used in chemotherapy, such as cisplatin and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving cisplatin, fluorouracil, and gefitinib together with radiation therapy may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects of giving cisplatin, fluorouracil, and gefitinib together with hyperfractionated radiation therapy and to see how well they work in treating patients with locally advanced head and neck cancer.


Condition Intervention Phase
Head and Neck Cancer
Drug: cisplatin
Drug: fluorouracil
Drug: Iressa
Radiation: hyperfractionated radiation therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of Concurrent Chemotherapy and ZD1839 (IRESSA) With Hyperfractionated Radiation Therapy, Followed by Maintenance ZD1839 (IRESSA) for Patients With Locally Advanced Squamous Cell Head and Neck Cancer

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • Number of Patients Treated With ZD1839 With Chemotherapy and Hyperfractionated Radiation That Had a 1-year Survival [ Time Frame: at 1 year after start of treatment ] [ Designated as safety issue: No ]
    To explore the activity of ZD1839 with chemotherapy and hyperfractionated radiation using 1-year survival

  • Number of Participants With No Distant Metastatic Disease at 1 Year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    1-year distant metastatic disease control in patients with locally advanced squamous cell head and neck cancer. Distant disease means that cancer came back in sites outside of the head and neck.


Secondary Outcome Measures:
  • Number of Participants With No Local Disease at 1 Year [ Time Frame: at 1 year after start of treatment ] [ Designated as safety issue: No ]
    Number of Participants with No Local Disease at 1 Year. Local disease means that the cancer came back in the same site.

  • Number of Patients With Greater Than or Equal to Mild (Grade 1) Toxicity [ Time Frame: at 1 year after start of treatment ] [ Designated as safety issue: Yes ]
    Any toxicity greater than or equal to Grade 1= mild

  • Number of Patients With a Complete Response Defined as Complete Disappearance of All Clinically Detectable Tumor. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Complete response rate per RECIST Criteria (CTC V3)

  • Number of Participants Who Completed 2 Years of Therapy [ Time Frame: at 2 years after start of treatment ] [ Designated as safety issue: Yes ]

Enrollment: 60
Study Start Date: April 2006
Study Completion Date: May 2010
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Concurrent Chemotherapy and ZD1839 Drug: cisplatin
20mg/m2/d IV continuous infusion x4 days
Other Name: CDDP
Drug: fluorouracil
1000mg.m2/d IV continuous x 4 days
Other Name: 5FU
Drug: Iressa
250mg/PO qd x 2 years
Other Name: ZD1839
Radiation: hyperfractionated radiation therapy
120cGy bid
Other Name: hyperfractionated radiation therapy

Detailed Description:

OBJECTIVES:

Primary

  • Explore the activity of cisplatin, fluorouracil, gefitinib, and hyperfractionated radiotherapy, in terms of 1-year survival and 1-year distant metastatic disease control, in patients with locally advanced squamous cell carcinoma of the head and neck.

Secondary

  • Explore the activity of this regimen, in terms of disease-specific survival and local control, in these patients.
  • Assess the toxicity of this regimen in these patients.
  • Assess the complete response rate in patients treated with this regimen.
  • Assess the toxicity and tolerability of long-term maintenance with gefitinib in patients rendered disease free after this treatment regimen.

OUTLINE: Patients undergo hyperfractionated radiotherapy twice daily, 5 days a week, beginning on day 1 and continuing for 6 weeks. Patients also receive fluorouracil IV continuously over 96 hours and cisplatin IV continuously over 96 hours on days 1-4 and 22-25 and oral gefitinib beginning once daily on day 1 and continuing for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3-6 months.

PROJECTED ACCRUAL: A total of 60 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 primary* squamous cell carcinoma of the head and neck region, excluding any of the following:

    • Nasopharynx
    • Paranasal sinuses
    • Salivary glands NOTE: *Primary site must be identified
  • Locoregionally confined stage III or IV disease

    • No evidence of nodal disease below the clavicles
    • No distant hematogenous metastases (M0)

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • WBC > 3,500/mm³
  • Platelet count > 100,000/mm³
  • Creatinine ≤ 2.0 mg/dL
  • Alkaline phosphatase < 2 times normal
  • AST < 2 times normal
  • Bilirubin ≤ 2.0 mg/dL
  • Calcium normal
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • Must not be a poor compliance risk for follow-up
  • No known severe hypersensitivity to gefitinib or any excipients of this drug
  • No evidence of clinically active interstitial lung disease

    • Patients with chronic, stable radiographic changes who are asymptomatic are eligible
  • No unstable or uncontrolled angina, clinically apparent jaundice, or active infection
  • No history of any other malignancy (except squamous cell or basal cell skin cancer or cervical carcinoma in situ) unless disease free for ≥ 5 years
  • No other severe, uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease)

PRIOR CONCURRENT THERAPY:

  • Recovered from prior oncologic or other major surgery
  • No prior definitive surgery, radiotherapy, chemotherapy, immunotherapy, or epidermal growth factor receptor inhibitors for head and neck cancer
  • No investigational drugs within the past 30 days
  • No concurrent CYP3A4 inducers, including any of the following:

    • Phenytoin
    • Carbamazepine
    • Rifampin
    • Phenobarbital
    • Hypericum perforatum (St. John's wort)
  • Concurrent surgery allowed provided gefitinib is not administered 2 weeks before and 2 weeks after surgery
  • No concurrent aminoglycoside antibiotics
  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: NCT00352105

Locations
United States, Ohio
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
David Adelstein
Investigators
Study Chair: David J. Adelstein, MD Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: David Adelstein, Principal Investigator, Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00352105     History of Changes
Other Study ID Numbers: CCF5842, P30CA043703, CCF-5842, ZENECA-1839/0235
Study First Received: July 13, 2006
Results First Received: November 17, 2011
Last Updated: November 1, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Case Comprehensive Cancer Center:
stage III squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the larynx
stage IV squamous cell carcinoma of the larynx
stage III squamous cell carcinoma of the lip and oral cavity
stage IV squamous cell carcinoma of the lip and oral cavity
stage III squamous cell carcinoma of the oropharynx
stage IV squamous cell carcinoma of the oropharynx

Additional relevant MeSH terms:
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Cisplatin
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 16, 2014