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

Phase 2

Active, not recruiting

• Conditions: Head and Neck Cancer
• Interventions: 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

• Registration Number: NCT00544414
• Lead Sponsor: City of Hope Medical Center

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.

Basic Information
|
Recruitment & Eligibility
|
Study & Design

Study Timeline

• Study Start: 2000-06-07
• Study First Submitted: 2007-10-13
• Study First Submitted QC: 2007-10-13
• Study First Posted: 2007-10-16
• Primary Completion: 2017-02-14
• Results First Submitted: 2023-03-10
• Results First Submitted QC: 2023-04-06
• Results First Posted: 2023-04-07
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-26
• Last Update Posted: 2024-02-29
• Study Completion: 2024-12-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 31

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment	gemcitabine hydrochloride	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.
Treatment	leucovorin calcium	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.
Treatment	gene expression analysis	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.
Treatment	quality-of-life assessment	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.
Treatment	biopsy	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.
Treatment	conventional surgery	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.
Treatment	neoadjuvant therapy	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.
Treatment	protein expression analysis	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.
Treatment	laboratory biomarker analysis	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.
Treatment	adjuvant therapy	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.
Treatment	radiation therapy	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.
Treatment	cisplatin	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.
Treatment	docetaxel	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.
Treatment	fluorouracil	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.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival	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.
Overall Response	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.