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

February 26, 2024 updated by: City of Hope Medical Center

Multimodality Management of Head and Neck Cancer: A Phase II Trial of Induction Chemotherapy, Organ Preservation Surgery, and Concurrent Chemoradiotherapy

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

31

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 second to 120 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment

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.

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.
Genetic: gene expression analysis
Drug: docetaxel
Drug: fluorouracil
Drug: leucovorin calcium
Radiation: radiation therapy
Genetic: protein expression analysis
Other: laboratory biomarker analysis
Procedure: adjuvant therapy
Procedure: biopsy
Procedure: neoadjuvant therapy
Drug: cisplatin
Drug: gemcitabine hydrochloride
Procedure: conventional surgery
Procedure: quality-of-life assessment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response
Time Frame: 30 days after last course of treatment
Complete response (CR): Complete disappearance of all measurable and evaluable disease. No new lesions. Partial response (PR): Greater than or equal 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No new lesions. All measurable and evaluable lesions and sites must be assessed using the same techniques as baseline. Overall Response (OR) = CR + PR.
30 days after last course of treatment
Progression-free Survival
Time Frame: From date of initial treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 171 months
Estimated using the product-limit method of Kaplan and Meier. Progression defined as a 50% increase or an increase of 10 cm^2 (whichever is smaller) in the sum of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, or clear worsening of any evaluable disease, or reappearance of any lesion that had disappeared, or appearance of any new lesion/site, or failure to return for evaluation due to death or deteriorating condition. Progression-free survival defined as from first day of treatment until the date of first documented progression or date of death from any cause, whichever came first. If failure has not occurred, failure time is censored at the time of last follow-up.
From date of initial treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 171 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Treatment-associated morbidity
Time Frame: 30 days after last course of treatment
30 days after last course of treatment
Comparison of diagnostic salivary cytology with histopathology at initial diagnosis and at follow-up
Time Frame: 30 days after last course of treatment
30 days after last course of treatment
Tolerability
Time Frame: 30 days after last course of treatment
30 days after last course of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Stephen I. Shibata, MD, City of Hope Comprehensive Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 7, 2000

Primary Completion (Actual)

February 14, 2017

Study Completion (Estimated)

December 30, 2024

Study Registration Dates

First Submitted

October 13, 2007

First Submitted That Met QC Criteria

October 13, 2007

First Posted (Estimated)

October 16, 2007

Study Record Updates

Last Update Posted (Estimated)

February 29, 2024

Last Update Submitted That Met QC Criteria

February 26, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 98147
  • P30CA033572 (U.S. NIH Grant/Contract)
  • CHNMC-98147
  • CDR0000566884 (Registry Identifier: NCI PDQ)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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