Clinical trial NCT00566540: Ph 2 Intensification Regimen for Previously Untreated, Resectable, Advanced Squamous Cell Cancer
Official title: Intensification Regimen for Previously Untreated, Resectable, Advanced Squamous Cell Carcinoma of the Oral Cavity, Oropharynx, and Hypopharynx: Incorporation of Intensity Modulated Radiotherapy and Submandibular Gland Transfer to Minimize Treatment Morbidity; Correlative Imaging/Molecular Markers.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Head and Neck Cancer
Keywords: stage III squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the lip and oral cavity
stage IV squamous cell carcinoma of the lip and oral cavity
stage III squamous cell carcinoma of the oropharynx
stage IV squamous cell carcinoma of the oropharynx
stage II squamous cell carcinoma of the hypopharynx
Lead sponsor: Ohio State University Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2007-12-03
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

PURPOSE: This phase II trial is studying how well giving cisplatin and paclitaxel together with radiation therapy and surgery works in treating patients with advanced cancer of the oral cavity, oropharynx, or hypopharynx that can be removed by surgery.

Detailed description: OBJECTIVES:

Primary

* Determine the feasibility of a new intensification regimen comprising cisplatin and paclitaxel in combination with radiotherapy and surgery in patients with resectable advanced squamous cell carcinoma of the oral cavity, oropharynx, or hypopharynx.

Secondary

* Assess the disease-free interval and failure sites in patients treated with this regimen.
* Correlate molecular markers with treatment outcome in these patients.
* Correlate quality of life with treatment outcome in these patients.
* Determine the frequency and severity of toxicities of this regimen in these patients.
* Evaluate treatment completion in these patients.

OUTLINE:

* Preoperative therapy (weeks 1 and 2): Patients receive cisplatin IV over 2 hours on days 1-3. Patients also undergo intensity-modulated external beam radiotherapy once daily on days 1-5 and 8-12.
* Surgery (week 3): Patients undergo surgical resection of the primary tumor (with or without neck dissection) and intraoperative boost radiotherapy.
* Postoperative therapy (weeks 7-10): Patients receive cisplatin IV over 2 hours on days 1-3 and 22-24 and paclitaxel IV over 3 hours on days 1, 8, 15, and 22. Patients also undergo intensity-modulated external beam radiotherapy on days 1-5, 8-12, 15-19, and 22-26.

Patients undergo blood and tissue sample collection at baseline, in weeks 3, 7-10, and 14, and then periodically thereafter for biomarker correlative studies.

Quality of life is assessed at baseline, at 3, 6, and 12 months after completion of treatment, and then annually thereafter.

After completion of study treatment, patients are followed every 2 months for 1 year and then periodically thereafter.

Eligibility criteria: Inclusion Criteria:

* Patients must have a Karnofsky Performance Index ≥60%
* Patients must be over the age of 18.
* Patients must have a life expectancy of at least 6 months.
* Women of childbearing age must have a negative serum pregnancy test and agree to use an effective method of contraceptive.
* Patients with a cardiac history should be cleared with a medical internist. In general, patients with a history of prior bradyarrythmias, atrioventricular (AV) conduction defects or marginal cardiac function will be eligible.
* Patients must have resectable stage III, stage IVA, stage IVB (without distant metastases) squamous cell carcinoma of the oral cavity, oropharynx, or hypopharynx. Hypopharyngeal carcinomas may also be stage II.
* Patients must not have had prior chemotherapy or radiotherapy (to the primary site or nodes).
* Patients may not be planning to receive while on study concomitant immunotherapy or hormonal therapy, except oral contraceptives or hormone replacement therapy.
* Patients must have adequate hepatic function documented by a normal serum bilirubin 0- 1.5mg/L and serum transaminases \< 4 x upper limit.
* Patients must have adequate renal function documented by a serum creatinine not above upper institutional normal limits and/or 24 hour OR calculated creatinine clearance \>60 ml/min. using the following formula:

  (140-age) x Wt (kg) x .85 (if Estimated Creatinine Clearance = 72 x Creatinine (mg/dl) female)
* Patients must have adequate bone marrow function documented by platelet count ≥ 100,000 and absolute neutrophil count ≥ 2,000.
* Patients will have surgery according to Section 5.3. Operative and pathology reports must be sufficiently detailed to confirm that surgery was done according to the guidelines.
* Patients must be examined by a multi-modality team (consisting of a head and neck surgeon, medical oncologist, and radiation oncologist) prior to entry on study.
* All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.

Exclusion Criteria:

* Distant metastases.
* Prior malignancy, except for 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 five years.
* Any condition that would be considered a contraindication for fluid challenge.
* Pregnant or lactating women may not participate.
* History of demyelinating neurological disorder, such as multiple sclerosis
* History of pancytopenia or aplastic anemia.

Primary outcomes:
measure: Feasibility of Treatment
timeFrame: Up to one year
Secondary outcomes:
measure: Disease-free Interval and Failure Sites
timeFrame: Up to one year
measure: Correlation of Quality of Life With Treatment Outcome
timeFrame: Up to one year
measure: Percentage of Participants With Serious Adverse Events
timeFrame: Up to one year
measure: Treatment Completion
timeFrame: up to one year
Other outcomes:
measure: Correlation of Molecular Markers With Treatment Outcome
timeFrame: Up to week 14
Locations:
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
Study officials:
affiliation: Ohio State University
name: Enver Ozer, MD
role: PRINCIPAL_INVESTIGATOR
References: