High-Dose Radiation Therapy Plus Chemotherapy in Treating Patients With Advanced Nose or Throat Cancer

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00052429
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 25
• Location: 1
• Arm: 1
• Duration (Months): 98
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

RATIONALE: Radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining high-dose radiation with chemotherapy may kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of combining high-dose radiation therapy with chemotherapy in treating patients who have newly diagnosed stage II, stage III, or stage IV nasopharyngeal cancer.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Drug: cisplatin; Drug: fluorouracil; Procedure: adjuvant therapy; Radiation: radiation therapy	Phase 1/Phase 2

Detailed Description

OUTLINE: Cohorts of 10 patients receive the following treatment to assess for dose-limiting toxicity.

Phase I

• Radiotherapy: Patients receive radiotherapy once daily 5 days a week for 6 weeks beginning on day 1.

• Concurrent chemotherapy: Patients receive cisplatin IV over 20-30 minutes on days 1-5 and 22-26.

• Adjuvant chemotherapy: Approximately 2-5 weeks after the completion of radiotherapy, patients receive fluorouracil IV continuously on days 1-4 and cisplatin IV over 20-30 minutes on days 1-5 and 22-26. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.

In the absence of dose-limiting toxicity in 1 whole cohort of patients, study proceeds to phase II.

Phase II

• Patients are treated as in phase I. Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Study of Dose-Painting Using Intensity Modulated Radiation Therapy Plus Chemotherapy in Patients With Stage II-IVB Nasopharyngeal Carcinoma
• Study Start Date: Sep 1, 2002
• Actual Primary Completion Date: Nov 1, 2010
• Actual Study Completion Date: Nov 1, 2010

Arms and Interventions

Arm

Intervention/Treatment

Experimental: High-Dose Radiation Therapy Plus Chemotherapy Phase I Radiotherapy: Patients receive radiotherapy once daily 5 days a week for 6 weeks beginning on day 1. Concurrent chemotherapy: Patients receive cisplatin IV over 20-30 minutes on days 1-5 and 22-26. Adjuvant chemotherapy: Approximately 2-5 weeks after the completion of radiotherapy, patients receive fluorouracil IV continuously on days 1-4 and cisplatin IV over 20-30 minutes on days 1-5 and 22-26. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. In the absence of dose-limiting toxicity in 1 whole cohort of patients, study proceeds to phase II. Phase II Patients are treated as in phase I. Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

Drug: cisplatin; Drug: fluorouracil; Procedure: adjuvant therapy; Radiation: radiation therapy

Outcome Measures

Primary Outcome Measures

1. Survival Rate of Patients [up to 77 months]

   Patients will be followed indefinitely and will have standard screening for development of distant metastases, including physical exam, as well as liver function tests and a chest radiograph annually. Patients will be classified as progression free as long as they remain alive with local, regional or distant recurrence.

2. Local Control of Participants [every 3 months in the first year of follow-up, every 4 months in the second year, every 6 months in the third-fifth years and annually, thereafter.]

   Patients will be classified as controlled as long as there is no clinical or radiographic evidence of disease progression. Physical exam with fiberoptic nasopharyngoscopy will be performed approximately every 3 months in the first year of follow-up, every 4 months in the second year, every 6 months in the third-fifth years and annually, thereafter.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed nasopharyngeal cancer

• Stage II-IVB

• Newly diagnosed

• No distant metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• WBC at least 3,000/mm^3

• Granulocyte count at least 1,500/mm^3

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

• Hemoglobin at least 8 g/dL

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)

• Alkaline phosphatase no greater than 2.5 times ULN

• AST no greater than 2.5 times ULN

Renal

• Creatinine no greater than 1.5 mg/dL

• Creatinine clearance at least 60 mL/min

• Calcium no greater than 11.5 mg/dL

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Medically able to tolerate a definitive course of radiotherapy and the necessary immobilization

• No other active malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy for this diagnosis

• More than 3 years since other prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for this diagnosis

• More than 3 years since other prior radiotherapy

• No prior radiotherapy to the head and neck region

Surgery

• Not specified

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan - Kettering Cancer Center	New York	New York	United States	10021

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center
• National Cancer Institute (NCI)

Investigators

• Study Chair: Suzanne Wolden, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Memorial Sloan Kettering Cancer Center

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00052429
• Other Study ID Numbers: 02-077; MSKCC-02077; NCI-H02-0101
• First Posted: Jan 27, 2003
• Last Update Posted: Jan 9, 2018
• Last Verified: Dec 1, 2017

• Keywords provided by Memorial Sloan Kettering Cancer Center: stage II lymphoepithelioma of the nasopharynx; stage II squamous cell carcinoma of the nasopharynx; stage III lymphoepithelioma of the nasopharynx; stage III squamous cell carcinoma of the nasopharynx; stage IV lymphoepithelioma of the nasopharynx; stage IV squamous cell carcinoma of the nasopharynx
• Additional relevant MeSH terms: Head and Neck Neoplasms; Fluorouracil

Study Results

Participant Flow

Arm/Group Title	High-Dose Radiation Therapy Plus Chemotherapy
Arm/Group Description	Phase I Radiotherapy: Patients receive radiotherapy once daily 5 days a week for 6 weeks beginning on day 1. Concurrent chemotherapy: Patients receive cisplatin IV over 20-30 minutes on days 1-5 and 22-26. Adjuvant chemotherapy: Approximately 2-5 weeks after the completion of radiotherapy, patients receive fluorouracil IV continuously on days 1-4 and cisplatin IV over 20-30 minutes on days 1-5 and 22-26. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. In the absence of dose-limiting toxicity in 1 whole cohort of patients, study proceeds to phase II. Phase II Patients are treated as in phase I. Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.
Period Title: Overall Study
STARTED	25
COMPLETED	25
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	High-Dose Radiation Therapy Plus Chemotherapy
Arm/Group Description	Phase I Radiotherapy: Patients receive radiotherapy once daily 5 days a week for 6 weeks beginning on day 1. Concurrent chemotherapy: Patients receive cisplatin IV over 20-30 minutes on days 1-5 and 22-26. Adjuvant chemotherapy: Approximately 2-5 weeks after the completion of radiotherapy, patients receive fluorouracil IV continuously on days 1-4 and cisplatin IV over 20-30 minutes on days 1-5 and 22-26. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. In the absence of dose-limiting toxicity in 1 whole cohort of patients, study proceeds to phase II. Phase II Patients are treated as in phase I. Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.
Overall Participants	25
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	22 88%
>=65 years	3 12%
Sex: Female, Male (Count of Participants)
Female	8 32%
Male	17 68%
Region of Enrollment (participants) [Number]
United States	25 100%

Outcome Measures

1. Primary Outcome

Title	Survival Rate of Patients
Description	Patients will be followed indefinitely and will have standard screening for development of distant metastases, including physical exam, as well as liver function tests and a chest radiograph annually. Patients will be classified as progression free as long as they remain alive with local, regional or distant recurrence.
Time Frame	up to 77 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High-Dose Radiation Therapy Plus Chemotherapy
Arm/Group Description	Phase I Radiotherapy: Patients receive radiotherapy once daily 5 days a week for 6 weeks beginning on day 1. Concurrent chemotherapy: Patients receive cisplatin IV over 20-30 minutes on days 1-5 and 22-26. Adjuvant chemotherapy: Approximately 2-5 weeks after the completion of radiotherapy, patients receive fluorouracil IV continuously on days 1-4 and cisplatin IV over 20-30 minutes on days 1-5 and 22-26. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. In the absence of dose-limiting toxicity in 1 whole cohort of patients, study proceeds to phase II. Phase II Patients are treated as in phase I. Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.
Measure Participants	25
Median (Full Range) [months]	33

2. Primary Outcome

Title	Local Control of Participants
Description	Patients will be classified as controlled as long as there is no clinical or radiographic evidence of disease progression. Physical exam with fiberoptic nasopharyngoscopy will be performed approximately every 3 months in the first year of follow-up, every 4 months in the second year, every 6 months in the third-fifth years and annually, thereafter.
Time Frame	every 3 months in the first year of follow-up, every 4 months in the second year, every 6 months in the third-fifth years and annually, thereafter.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High-Dose Radiation Therapy Plus Chemotherapy
Arm/Group Description	Phase I Radiotherapy: Patients receive radiotherapy once daily 5 days a week for 6 weeks beginning on day 1. Concurrent chemotherapy: Patients receive cisplatin IV over 20-30 minutes on days 1-5 and 22-26. Adjuvant chemotherapy: Approximately 2-5 weeks after the completion of radiotherapy, patients receive fluorouracil IV continuously on days 1-4 and cisplatin IV over 20-30 minutes on days 1-5 and 22-26. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. In the absence of dose-limiting toxicity in 1 whole cohort of patients, study proceeds to phase II. Phase II Patients are treated as in phase I. Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.
Measure Participants	25
Actuarial rate of local control	91 364%
Regional control	91 364%
Metastases-free survival	91 364%
Overall survival	89 356%

Adverse Events

Arm/Group Title	High-Dose Radiation Therapy Plus Chemotherapy
Arm/Group Description	Phase I Radiotherapy: Patients receive radiotherapy once daily 5 days a week for 6 weeks beginning on day 1. Concurrent chemotherapy: Patients receive cisplatin IV over 20-30 minutes on days 1-5 and 22-26. Adjuvant chemotherapy: Approximately 2-5 weeks after the completion of radiotherapy, patients receive fluorouracil IV continuously on days 1-4 and cisplatin IV over 20-30 minutes on days 1-5 and 22-26. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. In the absence of dose-limiting toxicity in 1 whole cohort of patients, study proceeds to phase II. Phase II Patients are treated as in phase I. Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.
All Cause Mortality
	High-Dose Radiation Therapy Plus Chemotherapy
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	High-Dose Radiation Therapy Plus Chemotherapy
	Affected / at Risk (%)	# Events
Total	19/25 (76%)
Blood and lymphatic system disorders
Febrile neutropenia	2/25 (8%)	4
Cardiac disorders
Sinus tachycardia	1/25 (4%)	1
Gastrointestinal disorders
Constipation	2/25 (8%)	2
Diarrhea	2/25 (8%)	3
Dysphagia	1/25 (4%)	1
Gastrointestinal disorder	1/25 (4%)	1
Mucositis-Oral cavity	3/25 (12%)	3
Nausea	5/25 (20%)	7
Abdominal pain	3/25 (12%)	3
Vomiting	6/25 (24%)	8
General disorders
Fatigue	2/25 (8%)	2
Fever	3/25 (12%)	3
Chills	3/25 (12%)	3
Infections and infestations
Infectious meningitis	1/25 (4%)	1
Investigations
Creatinine increased	1/25 (4%)	1
Platelet count decrease	1/25 (4%)	2
Metabolism and nutrition disorders
Dehydration	7/25 (28%)	9
Hypomagnesemia	1/25 (4%)	1
Hypokalemia	2/25 (8%)	2
Hyponatremia	1/25 (4%)	2
Musculoskeletal and connective tissue disorders
Neck pain	1/25 (4%)	1
Nervous system disorders
Central nervous system necrosis	3/25 (12%)	3
Dizziness	1/25 (4%)	1
Syncope	2/25 (8%)	2
Vasovagal reaction	1/25 (4%)	1
Psychiatric disorders
Anxiety	1/25 (4%)	1
Renal and urinary disorders
Renal and urinary disorders -Other, specify-Renal tubular disorder	1/25 (4%)	1
Urinary retention	1/25 (4%)	1
Reproductive system and breast disorders
Gynecomastia	1/25 (4%)	1
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain	1/25 (4%)	1
Vascular disorders
Hematoma	1/25 (4%)	1
Hypotension	3/25 (12%)	4
Other (Not Including Serious) Adverse Events
	High-Dose Radiation Therapy Plus Chemotherapy
	Affected / at Risk (%)	# Events
Total	22/25 (88%)
Ear and labyrinth disorders
Ear disorder	2/25 (8%)	2
Tinnitus	6/25 (24%)	6
Gastrointestinal disorders
Mucositis-Oral	2/25 (8%)	4
Nausea	2/25 (8%)	2
Vomiting	2/25 (8%)	2
General disorders
Fatigue	4/25 (16%)	6
Respiratory, thoracic and mediastinal disorders
Pain - Throat/pharynx/larynx	4/25 (16%)	4
Skin and subcutaneous tissue disorders
Induration/fibrosis	2/25 (8%)	2

Limitations/Caveats

[Not Specified]

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.