Radiation Therapy With or Without Chemotherapy in Reducing Mouth Dryness in Patients With Nasopharyngeal Cancer

• Sponsor: Radiation Therapy Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00057785
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 68
• Locations: 17
• Arm: 1
• Duration (Months): 166
• Patients Per Site: 4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Giving radiation therapy in different ways may cause less damage to normal tissue, prevent or lessen mouth dryness, and may help patients live more comfortably. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with radiation therapy may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of specialized radiation therapy techniques with or without chemotherapy in reducing mouth dryness in patients who have nasopharyngeal cancer.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer; Oral Complications of Radiation Therapy; Radiation Toxicity	Drug: cisplatin; Drug: fluorouracil; Radiation: Intensity modulated radiation therapy	Phase 2

Detailed Description

OBJECTIVES:

• Determine the transportability of IMRT to a multi-institutional setting.

• Determine the rate of late xerostomia in patients with nasopharyngeal cancer treated with intensity-modulated radiotherapy (IMRT) with or without chemotherapy.

• Correlate reduction of side effects on salivary flow with compliance in patients treated with these regimens.

• Determine the rate of local-regional control, distant metastasis, and disease-free and overall survival of patients treated with these regimens.

• Determine the acute and late toxicity of these regimens in these patients.

• Determine chemotherapy compliance in patients treated with these regimens.

OUTLINE: Patients undergo daily intensity-modulated radiotherapy (IMRT) 5 days a week for approximately 6.5 weeks (total of 33 fractions) in the absence of disease progression or unacceptable toxicity.

Patients with stage T2b or greater and/or node-positive disease receive cisplatin IV over 20-30 minutes on days 1, 22, and 43 concurrently with IMRT followed by cisplatin IV over 20-30 minutes and fluorouracil IV over 96 hours starting on days 71, 99, and 127.

Quality of life is assessed through saliva measurement at baseline and then at 3, 6, and 12 months after IMRT.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 64 patients will be accrued for this study within 36-40 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 68 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study Of Intensity Modulated Radiation Therapy (IMRT) +/- Chemotherapy For Nasopharyngeal Cancer
• Study Start Date: Feb 1, 2003
• Actual Primary Completion Date: Feb 1, 2007
• Actual Study Completion Date: Dec 1, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: IMRT +/- chemotherapy Intensity modulated radiation therapy (IMRT) for all patients and chemotherapy (cisplatin and fluorouracil) for patients with stage ≥ T2b and/or N+

Drug: cisplatin; 100 mg/m^2 intravenously on days 1, 22, and 43 and 80 mg/m^2 intravenously on days 71, 99, and 127; Drug: fluorouracil; 1000 mg/m^2/day as 96-hour continuous infusion on days 71-74, 99-102, and 127-130; Radiation: Intensity modulated radiation therapy; The gross tumor and lymph node metastasis, Planning Target Volume (PTV) 70 (Clinical Target Volume [CTV] 70 with a 5 mm margin) will receive 70 Gy in 33 fractions at 2.12 Gy per fraction. Treatment will be delivered once daily, 5 fractions per week, over 6 weeks and 3 days.

Outcome Measures

Primary Outcome Measures

1. Protocol Compliance of Intensity-modulated Radiotherapy Treatment Delivered [From start of treatment to end of treatment]

   Patients scored by the study chairs as no variation or minor variation were considered compliant, while patients scored as major variation or inevaluable were considered non-compliant. The number being reported is the number non-compliant. A compliance rate of 90% was targeted with 75% or lower being considered unacceptable. Fifty-seven patients were required with types I and II error rates both 0.10. If 10 or more patients out of 57 were non-compliant, the treatment would be unacceptable, per a two-stage Fleming multiple testing procedure.

Secondary Outcome Measures

1. Rate of Xerostomia at 1 Year (Grade ≥ 2) [From start of treatment to 1 year]

2. Rate of Locoregional Control at 2 Years [From registration to 2 years]

3. Whole Mouth Saliva Output Relative to Pretreatment Measurements [From start of treatment to 1 year]

4. Other Acute and Late Toxicities [From start of treatment to last follow-up]

5. Chemotherapy Compliance [From start of treatment to end of treatment]

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:

• Histologically confirmed stage I-IVB squamous cell carcinoma of the nasopharynx

• WHO I-III

• No stage IVC disease

• No evidence of distant metastasis

• Measurable or evaluable disease

• Must have been treated with primary radiotherapy

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• White blood cell count (WBC) at least 4,000/mm^3

• Platelet count at least 100,000/mm^3

Hepatic

• Not specified

Renal

• Creatinine no greater than 1.6 mg/dL

• Creatinine clearance at least 60 mL/min

Other

• Not pregnant (If stage T2b or greater or node-positive disease)

• Negative pregnancy test (If stage T2b or greater or node-positive disease)

• No other prior head and neck cancer

• No other malignancy within the past 5 years except nonmelanoma skin cancer

• No active untreated infection

• No other major medical or psychiatric illness that would preclude study entry

• Nutritional and general physical condition compatible with radiotherapy NOTE: *If stage T2b or greater or node-positive disease

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• More than 6 months since prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics

• More than 6 months since prior radiotherapy for head and neck cancer

Surgery

• No prior head and neck surgery to the primary tumor or lymph nodes except incisional or excisional biopsies

Other

• No other concurrent experimental therapy for cancer

• No amifostine or pilocarpine during or for 3 months after radiotherapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Comprehensive Cancer Center at University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	University of California Davis Cancer Center	Davis	California	United States	95616
3	Radiological Associates of Sacramento Medical Group, Incorporated	Sacramento	California	United States	95815
4	UCSF Comprehensive Cancer Center	San Francisco	California	United States	94115
5	Northeast Georgia Medical Center	Gainesville	Georgia	United States	30501
6	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
7	Siteman Cancer Center at Barnes-Jewish Hospital	St Louis	Missouri	United States	63110
8	Monmouth Medical Center	Long Branch	New Jersey	United States	07740
9	Albuquerque Regional Medical Center at Lovelace Sandia Health System	Albuquerque	New Mexico	United States	87102
10	Akron City Hospital	Akron	Ohio	United States	44304
11	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania	United States	19107
12	Fox Chase-Temple Cancer Center	Philadelphia	Pennsylvania	United States	19111-2497
13	CCOP - MainLine Health	Wynnewood	Pennsylvania	United States	19096
14	M.D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030
15	Wilford Hall Medical Center	Lackland AFB	Texas	United States	78236
16	McKay-Dee Hospital Center	Ogden	Utah	United States	84403
17	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• Radiation Therapy Oncology Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: Nancy Lee, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Radiation Therapy Oncology Group
• ClinicalTrials.gov Identifier: NCT00057785
• Other Study ID Numbers: RTOG-0225; CDR0000269314
• First Posted: Apr 9, 2003
• Last Update Posted: Feb 17, 2017
• Last Verified: Dec 1, 2016

• Keywords provided by Radiation Therapy Oncology Group: oral complications of radiation therapy; radiation toxicity; stage I squamous cell carcinoma of the nasopharynx; stage II squamous cell carcinoma of the nasopharynx; stage III squamous cell carcinoma of the nasopharynx; stage IV squamous cell carcinoma of the nasopharynx
• Additional relevant MeSH terms: Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma; Fluorouracil

Study Results

Participant Flow

Arm/Group Title	IMRT +/- Chemotherapy
Arm/Group Description	Intensity modulated radiation therapy (IMRT) for all patients and chemotherapy (cisplatin and fluorouracil) for patients with stage ≥ T2b and/or N+
Period Title: Overall Study
STARTED	68
COMPLETED	68
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	IMRT +/- Chemotherapy
Arm/Group Description	Intensity modulated radiation therapy (IMRT) for all patients and chemotherapy (cisplatin and fluorouracil) for patients with stage ≥ T2b and/or N+
Overall Participants	68
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	48.5
Gender (Count of Participants)
Female	17 25%
Male	51 75%

Outcome Measures

1. Primary Outcome

Title	Protocol Compliance of Intensity-modulated Radiotherapy Treatment Delivered
Description	Patients scored by the study chairs as no variation or minor variation were considered compliant, while patients scored as major variation or inevaluable were considered non-compliant. The number being reported is the number non-compliant. A compliance rate of 90% was targeted with 75% or lower being considered unacceptable. Fifty-seven patients were required with types I and II error rates both 0.10. If 10 or more patients out of 57 were non-compliant, the treatment would be unacceptable, per a two-stage Fleming multiple testing procedure.
Time Frame	From start of treatment to end of treatment

Outcome Measure Data

Analysis Population Description

First 57 eligible patients who started study treatment.

Arm/Group Title	IMRT +/- Chemotherapy
Arm/Group Description	Intensity modulated radiation therapy (IMRT) for all patients and chemotherapy (cisplatin and fluorouracil) for patients with stage ≥ T2b and/or N+
Measure Participants	57
Number [participants]	9 13.2%

2. Secondary Outcome

Title	Rate of Xerostomia at 1 Year (Grade ≥ 2)
Time Frame	From start of treatment to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Rate of Locoregional Control at 2 Years
Time Frame	From registration to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Whole Mouth Saliva Output Relative to Pretreatment Measurements
Time Frame	From start of treatment to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Other Acute and Late Toxicities
Time Frame	From start of treatment to last follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Chemotherapy Compliance
Time Frame	From start of treatment to end of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Adverse Event Reporting Description	Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for nonserious adverse events (AE).
Arm/Group Title	IMRT +/- Chemotherapy
Arm/Group Description	Intensity modulated radiation therapy (IMRT) for all patients and chemotherapy (cisplatin and fluorouracil) for patients with stage ≥ T2b and/or N+
All Cause Mortality
	IMRT +/- Chemotherapy
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	IMRT +/- Chemotherapy
	Affected / at Risk (%)	# Events
Total	55/68 (80.9%)
Blood and lymphatic system disorders
Febrile neutropenia	3/68 (4.4%)
Hemoglobin decreased	10/68 (14.7%)
Packed red blood cell transfusion	4/68 (5.9%)
Cardiac disorders
Edema NOS	1/68 (1.5%)
Left ventricular failure	1/68 (1.5%)
Sinus tachycardia	1/68 (1.5%)
Supraventricular arrhythmia NOS	1/68 (1.5%)
Ventricular arrhythmia NOS	1/68 (1.5%)
Ear and labyrinth disorders
Hearing impaired	8/68 (11.8%)
Hearing-Other	3/68 (4.4%)
Otitis externa (exc boil of meatus) NOS	2/68 (2.9%)
Endocrine disorders
Endocrine-Other	2/68 (2.9%)
Hypothyroidism	1/68 (1.5%)
Gastrointestinal disorders
Diarrhea NOS	1/68 (1.5%)
Dry mouth	3/68 (4.4%)
Dysphagia	16/68 (23.5%)
Esophageal spasm	6/68 (8.8%)
Esophagitis NOS	13/68 (19.1%)
Nausea	21/68 (30.9%)
Radiation mucositis	28/68 (41.2%)
Salivary gland disorder NOS	1/68 (1.5%)
Stomatitis	6/68 (8.8%)
Vomiting NOS	19/68 (27.9%)
General disorders
Fatigue	6/68 (8.8%)
Pain due to radiation	6/68 (8.8%)
Pain-other	6/68 (8.8%)
Pyrexia	1/68 (1.5%)
Infections and infestations
Implant infection	1/68 (1.5%)
Infection NOS	3/68 (4.4%)
Infection with grade 3 or 4 neutropenia	4/68 (5.9%)
Infection with unknown ANC	1/68 (1.5%)
Infection, Other	2/68 (2.9%)
Injury, poisoning and procedural complications
Dermatitis radiation NOS	6/68 (8.8%)
Investigations
Alanine aminotransferase increased	1/68 (1.5%)
Aspartate aminotransferase increased	1/68 (1.5%)
Blood creatinine increased	1/68 (1.5%)
CD4 lymphocytes decreased	1/68 (1.5%)
Inappropriate ADH secretion	1/68 (1.5%)
Leukocytes for BMT	1/68 (1.5%)
Leukopenia NOS	4/68 (5.9%)
Lymphopenia	11/68 (16.2%)
Neutropenia	20/68 (29.4%)
Platelet count decreased	4/68 (5.9%)
Weight decreased	12/68 (17.6%)
Weight increased	1/68 (1.5%)
Metabolism and nutrition disorders
Acidosis NOS	1/68 (1.5%)
Anorexia	7/68 (10.3%)
Blood albumin decreased	2/68 (2.9%)
Blood magnesium decreased	2/68 (2.9%)
Dehydration	11/68 (16.2%)
Hyperglycemia NOS	4/68 (5.9%)
Hyperkalemia	1/68 (1.5%)
Hypocalcemia	5/68 (7.4%)
Hypokalemia	8/68 (11.8%)
Hyponatremia	12/68 (17.6%)
Hypophosphatemia	2/68 (2.9%)
Musculoskeletal and connective tissue disorders
Joint, muscle, or bone-Other	1/68 (1.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain	1/68 (1.5%)
Nervous system disorders
Headache NOS	1/68 (1.5%)
Neurologic-Other	1/68 (1.5%)
Peripheral motor neuropathy	1/68 (1.5%)
Peripheral sensory neuropathy	1/68 (1.5%)
Syncope	3/68 (4.4%)
Psychiatric disorders
Anxiety NEC	1/68 (1.5%)
Depression NEC	1/68 (1.5%)
Hallucination NOS	2/68 (2.9%)
Renal and urinary disorders
Renal failure NOS	1/68 (1.5%)
Renal/GU-Other	2/68 (2.9%)
Respiratory, thoracic and mediastinal disorders
Dyspnea NOS	1/68 (1.5%)
Hypoxia	3/68 (4.4%)
Pneumonitis NOS	3/68 (4.4%)
Pulmonary-other	1/68 (1.5%)
Skin and subcutaneous tissue disorders
Erythema multiforme	1/68 (1.5%)
Skin-Other	2/68 (2.9%)
Vascular disorders
Hemorrhage NOS	1/68 (1.5%)
Hypotension NOS	6/68 (8.8%)
Thrombosis NOS	1/68 (1.5%)
Other (Not Including Serious) Adverse Events
	IMRT +/- Chemotherapy
	Affected / at Risk (%)	# Events
Total	68/68 (100%)
Blood and lymphatic system disorders
Hematologic-Other	8/68 (11.8%)
Hemoglobin decreased	51/68 (75%)
Cardiac disorders
Edema NOS	13/68 (19.1%)
Ear and labyrinth disorders
Earache	4/68 (5.9%)
Hearing impaired	33/68 (48.5%)
Hearing-Other	17/68 (25%)
Late RT toxicity: Auditory/hearing: NOS	32/68 (47.1%)
Otitis media serous NOS	7/68 (10.3%)
Endocrine disorders
Hypothyroidism	10/68 (14.7%)
Gastrointestinal disorders
Constipation	14/68 (20.6%)
Diarrhea NOS	9/68 (13.2%)
Dry mouth	61/68 (89.7%)
Dysphagia	24/68 (35.3%)
Esophagitis NOS	28/68 (41.2%)
GI-other	8/68 (11.8%)
Late RT toxicity: Esophagus: NOS	28/68 (41.2%)
Late RT toxicity: Larynx: NOS	13/68 (19.1%)
Late RT toxicity: Mucous membrane: NOS	41/68 (60.3%)
Late RT toxicity: Salivary gland: NOS	51/68 (75%)
Nausea	46/68 (67.6%)
Radiation mucositis	50/68 (73.5%)
Salivary gland disorder NOS	59/68 (86.8%)
Stomatitis	15/68 (22.1%)
Vomiting NOS	31/68 (45.6%)
General disorders
Fatigue	50/68 (73.5%)
Late RT toxicity: Other: NOS	33/68 (48.5%)
Pain due to radiation	24/68 (35.3%)
Pain-other	24/68 (35.3%)
Pyrexia	10/68 (14.7%)
Rigors	5/68 (7.4%)
Infections and infestations
Infection NOS	7/68 (10.3%)
Injury, poisoning and procedural complications
Dermatitis radiation NOS	43/68 (63.2%)
Late RT toxicity: Skin (within RT field): NOS	22/68 (32.4%)
Late RT toxicity: Subcutaneous tissue (within RT field): NOS	27/68 (39.7%)
Investigations
Alanine aminotransferase increased	13/68 (19.1%)
Aspartate aminotransferase increased	9/68 (13.2%)
Blood alkaline phosphatase NOS increased	9/68 (13.2%)
Blood bilirubin increased	6/68 (8.8%)
Blood creatinine increased	12/68 (17.6%)
Gamma-glutamyltransferase increased	5/68 (7.4%)
Leukopenia NOS	50/68 (73.5%)
Lymphopenia	16/68 (23.5%)
Metabolic-Other	7/68 (10.3%)
Neutropenia	33/68 (48.5%)
Platelet count decreased	18/68 (26.5%)
Weight decreased	40/68 (58.8%)
Metabolism and nutrition disorders
Anorexia	18/68 (26.5%)
Blood albumin decreased	19/68 (27.9%)
Blood magnesium decreased	15/68 (22.1%)
Dehydration	19/68 (27.9%)
Hyperglycemia NOS	16/68 (23.5%)
Hyperkalemia	7/68 (10.3%)
Hypocalcemia	17/68 (25%)
Hypokalemia	15/68 (22.1%)
Hyponatremia	26/68 (38.2%)
Hypophosphatemia	6/68 (8.8%)
Musculoskeletal and connective tissue disorders
Joint, muscle, or bone-Other	4/68 (5.9%)
Late RT toxicity: Bone (incl. osteonecrosis): NOS	4/68 (5.9%)
Late RT toxicity: Joint: NOS	13/68 (19.1%)
Nervous system disorders
Dizziness (exc vertigo)	4/68 (5.9%)
Headache NOS	10/68 (14.7%)
Neuralgia NOS	4/68 (5.9%)
Peripheral motor neuropathy	6/68 (8.8%)
Peripheral sensory neuropathy	23/68 (33.8%)
Taste disturbance	19/68 (27.9%)
Psychiatric disorders
Confusion	4/68 (5.9%)
Insomnia NEC	4/68 (5.9%)
Renal and urinary disorders
Renal/GU-Other	13/68 (19.1%)
Respiratory, thoracic and mediastinal disorders
Cough	11/68 (16.2%)
Dysphonia	5/68 (7.4%)
Dyspnea NOS	6/68 (8.8%)
Epistaxis	15/68 (22.1%)
Hiccups	5/68 (7.4%)
Pulmonary-other	4/68 (5.9%)
Rhinitis allergic NOS	5/68 (7.4%)
Skin and subcutaneous tissue disorders
Alopecia	20/68 (29.4%)
Dermatitis exfoliative NOS	6/68 (8.8%)
Erythema multiforme	6/68 (8.8%)
Skin discoloration	9/68 (13.2%)
Skin-Other	8/68 (11.8%)
Toxicoderma	4/68 (5.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.