Optimized Intensity Modulated Irradiation for Head and Neck Cancer

• Sponsor: University of Michigan Rogel Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00580983
• Collaborator: (none)
• Enrollment: 90
• Location: 1
• Arm: 1
• Duration (Months): 82
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

The purpose of this study is to test whether the use of advanced radiation therapy delivery techniques can spare a patient's normal tissue, including salivary glands, from radiation. This study is being done to try to reduce radiation side effects, especially mouth dryness, which happens with standard radiation methods. In order to reduce these side effects, other normal tissues may receive a different radiation dose (sometimes more) than what would have been received using standard radiation therapy. A secondary goal of this study is to determine if the type of tumor a patient has can be controlled at least as well (or better) using this advanced radiation therapy delivery technique as it would be if the patient was treated with standard radiation therapy.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Radiation: IMRT; Drug: Paclitaxel; Drug: Carboplatin; Drug: Cisplatin; Drug: 5-Fluorouracil	N/A

Detailed Description

Studies show that a dose response relationship in the salivary glands exists and that it may be possible to improve significantly post-radiation xerostomia and quality of life if radiation techniques can be devised that would spare the salivary glands while adequately treating the targets. A new treatment modality (computer-optimized IMRT) facilitates increased sparing of noninvolved tissue, specifically the sparing of both parotid glands, and more conformal high-dose delivery to the bilateral neck targets in patients with head and neck cancer. This study will evaluate the benefits regarding xerostomia-specific and general QOL in patients receiving head and neck RT using this modality. Assessment of swallowing dysfunction and aspiration will be made using videofluoroscopy. In addition, this study will evaluate the pattern of local/regional tumor recurrence, to assess whether sparing both parotid glands may cause tumor recurrence in spared neck areas.

Study Design

• Study Type: Interventional
• Actual Enrollment: 90 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Optimized Intensity Modulated Irradiation for Head and Neck Cancer
• Study Start Date: Aug 1, 2003
• Actual Primary Completion Date: Jun 1, 2010
• Actual Study Completion Date: Jun 1, 2010

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Chemo-IMRT Chemotherapy: Chemotherapy will consist of Paclitaxel 30mg/m² IV over 1 hour, followed by Carboplatin (AUC 1) IV over 30 minutes, or Carboplatin 100mg/m² per IV over 30 minutes or Cisplatin 100mg/m² per IV over 1 hour, or Cisplatin (80mg/m²) or Carboplatin (AUC 5) IV on day 1 and 5-Fluorouracil (1000mg/m²) as a 24-hour continuous infusion, daily x 4 days. Intensity-modulated Radiation Therapy (IMRT): Primary RT: 70 Gy to gross disease and 56-63 Gy to subclinical disease in 35 fractions. Post-operative RT: 64 Gy to high-risk targets (postoperative tumor bed, first-echelon nodes) and 57.6 Gy to low-risk targets, in 32 fractions.

Radiation: IMRT; Drug: Paclitaxel; Drug: Carboplatin; Drug: Cisplatin; Drug: 5-Fluorouracil

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Grade 0-1 Observer-rated Dysphagia [12 months]

   To objectively assess dysphagia and aspiration in patients receiving dysphagia/aspiration-sparing IMRT concurrent with chemotherapy, the percentage of participants with observer-rated dysphagia was calculated.

Secondary Outcome Measures

1. The Mean Esophageal Radiotherapy Dose in Patients With Strictures and Without Strictures [5 years]

   To assess the relationships between the mean radiotherapy dose delivered and objectively measured dysphagia.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• All patients must have histologically confirmed invasive cancer of the head and neck.

• Irradiation to both neck sides is required.

• Standard radiation techniques would irradiate most of both parotid glands to a high dose (>50 Gy). Patients with oropharyngeal, oral, nasopharyngeal, hypopharyngeal and advanced laryngeal cancer are expected to fulfill this requirement.

• Patients with resectable disease that is either measurable, evaluable or non-measurable disease (post-operative) will be eligible.

• Karnofsky performance status >60

• Patients receiving or not receiving chemotherapy are eligible.

• All patients must sign an informed consent.

• Pre-treatment laboratory criteria:

• WBC (White Blood Cell) > 3500/ul, granulocyte > 1500/ul.

• Platelet count > 100,000/ul.

• Creatinine clearance > 60 cc/min. to receive cisplatin; creatinine clearance 30-59 cc/min to receive carboplatin.

• Bilirubin < 1.5 mg% with no evidence of obstructive liver disease.

• AST (Aspartate Aminotransferase) and ALT (Alanine Aminotransferase) equal to or less than 2.5 x upper limit of normal.

Exclusion Criteria:

• Patients who received past irradiation to the head and neck are not eligible.

• Prior head and neck malignancy or history of other prior non-head and neck malignancy within the past 3 years.

• Prior head and neck radiation or prior chemotherapy.

• Documented evidence of distant metastases.

• Active infection.

• Pregnancy or lactation; patients must use effective contraception during the course of the clinical trial.

• Any medical or psychiatric illness which in the opinion of the principal investigator would compromise the patients ability to tolerate this treatment.

• Patients residing in prison.

• Age < 18 years.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan	Ann Arbor	Michigan	United States	48109-5010

Sponsors and Collaborators

• University of Michigan Rogel Cancer Center

Investigators

• Principal Investigator: Avraham Eisbruch, M.D., University of Michigan Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Michigan Rogel Cancer Center
• ClinicalTrials.gov Identifier: NCT00580983
• Other Study ID Numbers: UMCC 2-21; HUM 43020 Legacy 2002-513
• First Posted: Dec 27, 2007
• Last Update Posted: Sep 7, 2016
• Last Verified: Jul 1, 2016

• Keywords provided by University of Michigan Rogel Cancer Center: Head and Neck cancer
• Additional relevant MeSH terms: Head and Neck Neoplasms; Paclitaxel; Carboplatin; Fluorouracil

Study Results

Participant Flow

Pre-assignment Detail	90 participants were enrolled however only 80 started treatment. Only 73 participants completed treatment. 7 did not complete the 12 month post radiation therapy (RT)swallowing studies.

Arm/Group Title	Chemo-IMRT
Arm/Group Description	Chemotherapy: Chemotherapy will consist of Paclitaxel 30mg/m² IV over 1 hour, followed by Carboplatin (AUC 1) IV over 30 minutes, or Carboplatin 100mg/m² per IV over 30 minutes or Cisplatin 100mg/m² per IV over 1 hour, or Cisplatin (80mg/m²) or Carboplatin (AUC 5) IV on day 1 and 5-Fluorouracil (1000mg/m²) as a 24-hour continuous infusion, daily x 4 days. Intensity-modulated Radiation Therapy (IMRT): Primary RT: 70 Gy to gross disease and 56-63 Gy to subclinical disease in 35 fractions. Post-operative RT: 64 Gy to high-risk targets (postoperative tumor bed, first-echelon nodes) and 57.6 Gy to low-risk targets, in 32 fractions.
Period Title: Overall Study
STARTED	80
COMPLETED	73
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	Chemo-IMRT
Arm/Group Description	Chemotherapy: Chemotherapy will consist of Paclitaxel 30mg/m² IV over 1 hour, followed by Carboplatin (AUC 1) IV over 30 minutes, or Carboplatin 100mg/m² per IV over 30 minutes or Cisplatin 100mg/m² per IV over 1 hour, or Cisplatin (80mg/m²) or Carboplatin (AUC 5) IV on day 1 and 5-Fluorouracil (1000mg/m²) as a 24-hour continuous infusion, daily x 4 days. Intensity-modulated Radiation Therapy (IMRT): Primary RT: 70 Gy to gross disease and 56-63 Gy to subclinical disease in 35 fractions. Post-operative RT: 64 Gy to high-risk targets (postoperative tumor bed, first-echelon nodes) and 57.6 Gy to low-risk targets, in 32 fractions.
Overall Participants	73
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	55
Sex: Female, Male (Count of Participants)
Female	8 11%
Male	65 89%
Tumor Location (participants) [Number]
Tonsil	35 47.9%
Base of Tongue	38 52.1%
Gross Tumor Volume (mL) [Median (Full Range) ]
Median (Full Range) [mL]	110
T Stage (participants) [Number]
Stage 1	9 12.3%
Stage 2	29 39.7%
Stage 3	17 23.3%
Stage 4	18 24.7%
N Stage (participants) [Number]
Stage 0	6 8.2%
Stage 1	6 8.2%
Stage 2	55 75.3%
Stage 3	6 8.2%
AJCC Stage (participants) [Number]
Stage III	9 12.3%
Stage IVA	58 79.5%
Stage IVB	6 8.2%
Smoking Status (participants) [Number]
Never Smoked	26 35.6%
Previous Smoker	31 42.5%
Current Smoker	16 21.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Grade 0-1 Observer-rated Dysphagia
Description	To objectively assess dysphagia and aspiration in patients receiving dysphagia/aspiration-sparing IMRT concurrent with chemotherapy, the percentage of participants with observer-rated dysphagia was calculated.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

90 patients were enrolled. Only 80 patients were treated and 7 patients did not complete the 12 month post-Radiation Therapy (RT) swallowing studies. Therefore only 73 patients were analyzed.

Arm/Group Title	Chemo-IMRT
Arm/Group Description	Chemotherapy: Chemotherapy will consist of Paclitaxel 30mg/m² IV over 1 hour, followed by Carboplatin (AUC 1) IV over 30 minutes, or Carboplatin 100mg/m² per IV over 30 minutes or Cisplatin 100mg/m² per IV over 1 hour, or Cisplatin (80mg/m²) or Carboplatin (AUC 5) IV on day 1 and 5-Fluorouracil (1000mg/m²) as a 24-hour continuous infusion, daily x 4 days. Intensity-modulated Radiation Therapy (IMRT): Primary RT: 70 Gy to gross disease and 56-63 Gy to subclinical disease in 35 fractions. Post-operative RT: 64 Gy to high-risk targets (postoperative tumor bed, first-echelon nodes) and 57.6 Gy to low-risk targets, in 32 fractions.
Measure Participants	73
Number [percentage of participants]	94 128.8%

2. Secondary Outcome

Title	The Mean Esophageal Radiotherapy Dose in Patients With Strictures and Without Strictures
Description	To assess the relationships between the mean radiotherapy dose delivered and objectively measured dysphagia.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chemo-IMRT
Arm/Group Description	Chemotherapy: Chemotherapy will consist of Paclitaxel 30mg/m² IV over 1 hour, followed by Carboplatin (AUC 1) IV over 30 minutes, or Carboplatin 100mg/m² per IV over 30 minutes or Cisplatin 100mg/m² per IV over 1 hour, or Cisplatin (80mg/m²) or Carboplatin (AUC 5) IV on day 1 and 5-Fluorouracil (1000mg/m²) as a 24-hour continuous infusion, daily x 4 days. Intensity-modulated Radiation Therapy (IMRT): Primary RT: 70 Gy to gross disease and 56-63 Gy to subclinical disease in 35 fractions. Post-operative RT: 64 Gy to high-risk targets (postoperative tumor bed, first-echelon nodes) and 57.6 Gy to low-risk targets, in 32 fractions.
Measure Participants	73
Patients with Strictures (N=5)	48 (17)
Patients without strictures (N=68)	27 (12)

Adverse Events

Adverse Event Reporting Description	90 patients were enrolled. Only 80 patients were treated and 7 patients did not complete the 12 month post-Radiation Therapy (RT) swallowing studies. Therefore only 73 patients were included in the adverse events analysis.
Arm/Group Title	Chemo-IMRT
Arm/Group Description	Chemotherapy: Chemotherapy will consist of Paclitaxel 30mg/m² IV over 1 hour, followed by Carboplatin (AUC 1) IV over 30 minutes, or Carboplatin 100mg/m² per IV over 30 minutes or Cisplatin 100mg/m² per IV over 1 hour, or Cisplatin (80mg/m²) or Carboplatin (AUC 5) IV on day 1 and 5-Fluorouracil (1000mg/m²) as a 24-hour continuous infusion, daily x 4 days. Intensity-modulated Radiation Therapy (IMRT): Primary RT: 70 Gy to gross disease and 56-63 Gy to subclinical disease in 35 fractions. Post-operative RT: 64 Gy to high-risk targets (postoperative tumor bed, first-echelon nodes) and 57.6 Gy to low-risk targets, in 32 fractions.
All Cause Mortality
	Chemo-IMRT
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Chemo-IMRT
	Affected / at Risk (%)	# Events
Total	26/73 (35.6%)
Cardiac disorders
Hypertension	1/73 (1.4%)
Gastrointestinal disorders
Constipation	1/73 (1.4%)
Dobhoff Tube Complication	1/73 (1.4%)
Dysphagia	3/73 (4.1%)
Esophageal Stricture	1/73 (1.4%)
Mucositis	4/73 (5.5%)
Nausea	7/73 (9.6%)
Odynophagia	1/73 (1.4%)
Pharyngeal Stenosis	1/73 (1.4%)
Stomatitis	1/73 (1.4%)
Thrush	2/73 (2.7%)
Ulceration of the Mucous Membrane	1/73 (1.4%)
Vomiting	7/73 (9.6%)
General disorders
Death	1/73 (1.4%)
Fever	2/73 (2.7%)
Increased Mucous Secretions	1/73 (1.4%)
Neck Pain	2/73 (2.7%)
Neck Swelling	1/73 (1.4%)
Weight Loss	1/73 (1.4%)
Infections and infestations
Pneumonia	7/73 (9.6%)
Investigations
Hyperlipedemia	1/73 (1.4%)
Metabolism and nutrition disorders
Dehydration	3/73 (4.1%)
Poor Oral Intake	1/73 (1.4%)
Nervous system disorders
Headache	1/73 (1.4%)
Syncope	1/73 (1.4%)
Psychiatric disorders
Anxiety	1/73 (1.4%)
Mental Status Change	3/73 (4.1%)
Renal and urinary disorders
Urinary Tract Infection	1/73 (1.4%)
Respiratory, thoracic and mediastinal disorders
Hemoptysis	1/73 (1.4%)
Skin and subcutaneous tissue disorders
Induration of Skin	1/73 (1.4%)
Skin Redness	1/73 (1.4%)
Surgical and medical procedures
PEG Tube Complications	1/73 (1.4%)
Other (Not Including Serious) Adverse Events
	Chemo-IMRT
	Affected / at Risk (%)	# Events
Total	0/73 (0%)

Limitations/Caveats

No modeling of observer-rated posttherapy dysphagia was performed because of the small number (four) of patients with greater than, or equal to, Grade 2 after 6 months.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.