Clinical trial NCT00544414: Chemotherapy Followed by Surgery, Chemotherapy, and Radiation Therapy in Treating Patients With Locally Advanced Head And Neck Cancer
Official title: Multimodality Management of Head and Neck Cancer: A Phase II Trial of Induction Chemotherapy, Organ Preservation Surgery, and Concurrent Chemoradiotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Head and Neck Cancer
Keywords: 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
Lead sponsor: City of Hope Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-10-16
Enrollment: 31
Sex: ALL
Minimum age (years): 0
Maximum age (years): 120
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Overall Response
timeFrame: 30 days after last course of treatment
measure: Progression-free Survival
timeFrame: 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 outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: City of Hope Comprehensive Cancer Center
name: Stephen I. Shibata, MD
role: STUDY_CHAIR
References:
citation: Psyrri A, Rampias T, Vermorken JB. The current and future impact of human papillomavirus on treatment of squamous cell carcinoma of the head and neck. Ann Oncol. 2014 Nov;25(11):2101-2115. doi: 10.1093/annonc/mdu265. Epub 2014 Jul 23.