Chemotherapy Followed by Surgery, Chemotherapy, and Radiation Therapy in Treating Patients With Locally Advanced Head And Neck Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00544414
First received: October 13, 2007
Last updated: December 16, 2013
Last verified: December 2013
  Purpose

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs such as gemcitabine and cisplatin may make tumor cells more sensitive to radiation therapy. Giving combination chemotherapy before surgery or radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving chemotherapy followed by surgery, chemotherapy, and radiation therapy works in treating patients with locally advanced head and neck cancer.


Condition Intervention Phase
Head and Neck Cancer
Drug: cisplatin
Drug: docetaxel
Drug: fluorouracil
Drug: gemcitabine hydrochloride
Drug: leucovorin calcium
Genetic: gene expression analysis
Genetic: protein expression analysis
Other: laboratory biomarker analysis
Procedure: adjuvant therapy
Procedure: biopsy
Procedure: conventional surgery
Procedure: neoadjuvant therapy
Procedure: quality-of-life assessment
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: Multimodality Management of Head and Neck Cancer: A Phase II Trial of Induction Chemotherapy, Organ Preservation Surgery, and Concurrent Chemoradiotherapy

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Complete and overall response rate [ Designated as safety issue: No ]
  • Feasibility [ Designated as safety issue: No ]
  • Prospective impact of neoadjuvant chemotherapy, concurrent chemoradiotherapy, and organ preservation surgery on overall survival, time to progression, and pattern of disease recurrence [ Designated as safety issue: No ]
  • Biochemical correlates [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Treatment-associated morbidity [ Designated as safety issue: No ]
  • Comparison of diagnostic salivary cytology with histopathology at initial diagnosis and at follow-up [ Designated as safety issue: No ]
  • Tolerability [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: April 2000
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • To assess the complete and overall response rate of neoadjuvant docetaxel, cisplatin, fluorouracil, and leucovorin calcium in previously untreated patients with local regionally advanced head and neck cancer.
  • To evaluate the feasibility of a multimodality treatment approach with the goal of reducing long-term sequelae.
  • To evaluate prospectively, the impact of neoadjuvant chemotherapy, concurrent chemoradiotherapy, and organ preservation surgery on overall survival, time to progression, and pattern of disease recurrence in these patients.
  • To evaluate prospectively, biochemical correlates of response and prognosis, including markers such as thymidylate synthetase, ribonucleotide reductase, and ERCC1 (measured by quantitative PCR), p53 (evaluated by IHC), and HPV status and apoptosis (TUNEL assay).

Secondary

  • To evaluate treatment-associated morbidity with the use of a quality of life assessment tool.
  • To compare the results of diagnostic salivary cytology with those of histopathology at initial diagnosis as well as follow-up in head and neck cancer patients.
  • To evaluate the tolerability of combined chemoradiotherapy using gemcitabine and cisplatin after definitive surgery for squamous cell carcinoma of the head and neck.

OUTLINE: Patients receive neoadjuvant induction chemotherapy comprising docetaxel IV over 1 hour on day 1 and cisplatin IV, leucovorin IV, and fluorouracil IV over 24 hours on days 1-4. Induction chemotherapy repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.

Patients with partial response at the primary site may undergo radical or functional resection of the primary tumor within 3 weeks of completion of neoadjuvant therapy.

Beginning within 4 weeks of completion of neoadjuvant therapy, patients with persistent disease or complete response after chemotherapy at the primary or neck then undergo radiotherapy 5 days a week for 7 weeks and receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 60 minutes on day 1 of each week of radiotherapy in the absence of disease progression or unacceptable toxicity.

Patients complete the FACT-H&N quality of life questionnaire at baseline and at completion of neoadjuvant therapy.

Tissue biopsies are collected at baseline, periodically during therapy, at surgery, and after radiotherapy. Tissue is examined for gene and protein expression.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed squamous cell carcinoma of the head and neck, including any of the following subtypes:

    • Oral cavity
    • Oropharynx
    • Hypopharynx
    • Larynx
  • Stage III or IV disease

    • Stage II carcinoma of the larynx, hypopharynx, or base of tongue allowed
  • Measurable disease
  • Resectable disease, defined as tumors that are potentially curable by surgery and radiotherapy

PATIENT CHARACTERISTICS:

  • Karnofsky performance status ≥ 60%
  • ANC ≥ 1,500/μL
  • Platelet count ≥ 100,000/μL
  • Creatinine ≤ 1.5 mg/dL OR creatinine clearance > 60 mL/min
  • Bilirubin ≤ 1.5 mg/dL
  • Transaminases and alkaline phosphatase meeting 1 of the following criteria:

    • ALT or AST ≤ 2.5 times upper limit of normal (ULN) AND alkaline phosphatase normal
    • Alkaline phosphatase ≤ 4 times ULN AND ALT and AST normal
    • ALT or AST < 1.5 times ULN AND alkaline phosphatase < 2.5 times ULN
  • Free of serious infection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No prior malignancy allowed for purposes of determining disease-free or overall survival except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for 5 years
  • No unstable angina, history of congestive heart failure, or acute myocardial infarction within the past 6 months
  • No current symptomatic, neurosensory or neuromotor toxicity ≥ grade 2
  • No other significant medical or psychiatric condition incompatible with the protocol

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy or radiotherapy for head and neck cancer
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00544414

Sponsors and Collaborators
City of Hope Medical Center
Investigators
Study Chair: Stephen I. Shibata, MD Beckman Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT00544414     History of Changes
Other Study ID Numbers: 98147, P30CA033572, CHNMC-98147, CDR0000566884
Study First Received: October 13, 2007
Last Updated: December 16, 2013
Health Authority: United States: Federal Government

Keywords provided by City of Hope Medical Center:
stage III squamous cell carcinoma of the larynx
stage IV squamous cell carcinoma of the larynx
stage III squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the oropharynx
stage IV squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the oropharynx
stage III squamous cell carcinoma of the lip and oral cavity
stage IV squamous cell carcinoma of the lip and oral cavity
stage II squamous cell carcinoma of the larynx
stage II squamous cell carcinoma of the hypopharynx
stage II squamous cell carcinoma of the oropharynx

Additional relevant MeSH terms:
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Gemcitabine
Docetaxel
Cisplatin
Fluorouracil
Leucovorin
Levoleucovorin
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
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Antidotes
Protective Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Tubulin Modulators
Antimitotic Agents

ClinicalTrials.gov processed this record on August 26, 2014