Head and Neck Cancer
Conditions
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
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.
Interventions
DRUGCisplatin
Patients will receive Cisplatin (30 mg/m2 i.v.) daily x 3 days in week 1.
DRUGPaclitaxel
Patients will receive Paclitaxel (45 mg/m2i.v.) infusion over 3 hours during weeks 7,8,9,10
RADIATIONIntensity-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.
PROCEDURETriple 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.
Sponsors
Ohio State University Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of Treatment | Up to one year | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free Interval and Failure Sites | Up to one year | Assess disease-free interval and failure sites of a new treatment regimen. |
| Correlation of Quality of Life With Treatment Outcome | Up to one year | 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. |
| Percentage of Participants With Serious Adverse Events | Up to one year | Determine the frequency and severity of toxicities of the intensification regimen. Patients will be evaluated for local and systemic toxicity/morbidity from treatment regimen. |
| Treatment Completion | up to one year | Patients are to be seen at Ohio State Medical center for a physical exam every 2 months for the first year. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Correlation of Molecular Markers With Treatment Outcome | Up to week 14 | Evaluate potential correlative molecular markers with treatment outcome |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Neoadjuvant, Adjuvant Chemotherapy and Radiation) PREOPERATIVE:Patients receive cisplatin IV over 2 hours three times weekly in week 1 once daily(QD),5 days a week, in weeks 1-2.
SURGERY:Patients undergo triple endoscopy and biopsy with submandibular gland transfer in week 3.
INTRAOPERATIVE: Patients also undergo Intensity-Modulated Radiation Therapy (IMRT) External Beam Radiation.
POSTOPERATIVE: Patients receive paclitaxel IV over 3 hours in weeks 7-10 and cisplatin IV over 1-2 hours three times weekly in weeks 7 and 10. Patients also undergo Intensity-Modulated Radiation Therapy (IMRT) External Beam Radiation QD, 5 days a week, in weeks 7-10.
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 Intensity-Modulated Radiation Therapy (IMRT) External Beam Radiation: Patients will receive Intensity-Modulated Radiation Therapy (IMRT) External Beam Radiation to tumor and involved regional nod | 11 |
| Total | 11 |
Baseline characteristics
| Characteristic | Treatment (Neoadjuvant, Adjuvant Chemotherapy and Radiation) |
|---|---|
| Age, Continuous | 63 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment United States | 11 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 11 |
| other Total, other adverse events | 11 / 11 |
| serious Total, serious adverse events | 11 / 11 |
Outcome results
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
Time frame: Up to one year
Population: The data was not collected or analyzed due to discontinuation of study in early stages.
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.
Time frame: Up to one year
Population: The data analysis was unable to be completed due to discontinuation of study in early stages
Secondary
Disease-free Interval and Failure Sites
Assess disease-free interval and failure sites of a new treatment regimen.
Time frame: Up to one year
Population: The data was not collected or analyzed due to discontinuation of study in early stages.
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.
Time frame: Up to one year
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Neoadjuvant, Adjuvant Chemotherapy and Radiation) | Percentage of Participants With Serious Adverse Events | Leukocytes | 9 percentage of patients |
| Treatment (Neoadjuvant, Adjuvant Chemotherapy and Radiation) | Percentage of Participants With Serious Adverse Events | Rash | 9 percentage of patients |
| Treatment (Neoadjuvant, Adjuvant Chemotherapy and Radiation) | Percentage of Participants With Serious Adverse Events | Colitis | 9 percentage of patients |
| Treatment (Neoadjuvant, Adjuvant Chemotherapy and Radiation) | Percentage of Participants With Serious Adverse Events | Dehydration | 18 percentage of patients |
| Treatment (Neoadjuvant, Adjuvant Chemotherapy and Radiation) | Percentage of Participants With Serious Adverse Events | Diarrhea | 9 percentage of patients |
| Treatment (Neoadjuvant, Adjuvant Chemotherapy and Radiation) | Percentage of Participants With Serious Adverse Events | Vomiting | 9 percentage of patients |
| Treatment (Neoadjuvant, Adjuvant Chemotherapy and Radiation) | Percentage of Participants With Serious Adverse Events | Hemorrhage, Upper Respiratory | 9 percentage of patients |
| Treatment (Neoadjuvant, Adjuvant Chemotherapy and Radiation) | Percentage of Participants With Serious Adverse Events | Infection with normal ANC | 9 percentage of patients |
| Treatment (Neoadjuvant, Adjuvant Chemotherapy and Radiation) | Percentage of Participants With Serious Adverse Events | Edema | 9 percentage of patients |
Secondary
Treatment Completion
Patients are to be seen at Ohio State Medical center for a physical exam every 2 months for the first year.
Time frame: up to one year
Population: The data analysis was unable to be completed due to discontinuation of study in early stages
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Neoadjuvant, Adjuvant Chemotherapy and Radiation) | Treatment Completion | 7 patients |
Other Pre-specified
Correlation of Molecular Markers With Treatment Outcome
Evaluate potential correlative molecular markers with treatment outcome
Time frame: Up to week 14
Population: The data was not collected or analyzed due to discontinuation of study in early stages.