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

Head and Neck Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00544414
• Other study ID #: 98147
• Secondary ID: P30CA033572CHNMC
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 7, 2000
• Est. completion date: December 30, 2024

Study information

• Verified date: February 2024
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 31
• Est. completion date: December 30, 2024
• Est. primary completion date: February 14, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Drug:
• cisplatin

• docetaxel

• fluorouracil

• gemcitabine hydrochloride

• leucovorin calcium

Genetic:
• gene expression analysis

• protein expression analysis

Other:
• laboratory biomarker analysis

Procedure:
• adjuvant therapy

• biopsy

• conventional surgery

• neoadjuvant therapy

• quality-of-life assessment

Radiation:
• radiation therapy

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response	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
Primary	Progression-free Survival	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