Ph 2 Intensification Regimen for Previously Untreated, Resectable, Advanced Squamous Cell Cancer

Head and Neck Cancer Clinical Trial

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00566540
• Other study ID #: OSU-06026
• Secondary ID: NCI-2011-02687
• Status: Terminated
• Phase: Phase 2
• Start date: December 11, 2007
• Est. completion date: February 25, 2010

Study information

• Verified date: October 2021
• Source: Ohio State University Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: February 25, 2010
• Est. primary completion date: February 25, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Drug:
• Cisplatin
Patients will receive Cisplatin (30 mg/m2 i.v.) daily x 3 days in week 1.
• Paclitaxel
Patients will receive Paclitaxel (45 mg/m2i.v.) infusion over 3 hours during weeks 7,8,9,10

Radiation:
• Intensity-Modulated Radiation Therapy (IMRT) External Beam Radiation
Patients will receive Intensity-Modulated Radiation Therapy (IMRT) External Beam Radiation to tumor and involved regional nodes 20Gy over 10 daily (M-F) treatments (2 Gy Fractions with 6 millivolts photons)week 1 and 2.

Procedure:
• Triple endoscopy and biopsy
Resection of the primary tumor: Patients must have surgery performed according to the following surgical guidelines. The extent of the surgical resection will be dictated by the extent of the tumor at the time of initial evaluation. The primary lesion must be widely excised using accepted criteria for adequate excision depending on the region involved. All patients will undergo percutaneous endoscopic gastrostomy tube placement at the time of endoscopy and biopsies.

Locations

Country	Name	City	State
United States	Ohio State University Medical Center	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Ohio State University Comprehensive Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Correlation of Molecular Markers With Treatment Outcome	Evaluate potential correlative molecular markers with treatment outcome	Up to week 14
Primary	Feasibility of Treatment	Determine the feasibility of a new intensification regimen for previously untreated resectable advanced stage head and neck cancer that incorporates Cisplatin, Paclitaxel combined with surgery, submandibular gland transfer and radiation therapy	Up to one year
Secondary	Disease-free Interval and Failure Sites	Assess disease-free interval and failure sites of a new treatment regimen.	Up to one year
Secondary	Correlation of Quality of Life With Treatment Outcome	Assess quality of life with treatment outcome will be obtained at baseline (prior to treatment) and at 6 months post treatment and one year post-treatment follow-ups.	Up to one year
Secondary	Percentage of Participants With Serious Adverse Events	Determine the frequency and severity of toxicities of the intensification regimen. Patients will be evaluated for local and systemic toxicity/morbidity from treatment regimen.	Up to one year
Secondary	Treatment Completion	Patients are to be seen at Ohio State Medical center for a physical exam every 2 months for the first year.	up to one year

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