A Phase II Study of Concurrent Chemoradiotherapy Using Three-Dimensional Conformal Radiotherapy (3D-CRT) or Intensity-Modulated Radiation Therapy (IMRT) + Bevacizumab (BV) for Locally or Regionally Advanced Nasopharyngeal Cancer
Overview
- Phase
- Phase 2
- Intervention
- 3-Dimensional Conformal Radiation Therapy
- Conditions
- Stage II Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 46
- Locations
- 108
- Primary Endpoint
- Percentage of Patients With a Grade 4 Hemorrhage or Any Grade 5 Adverse Event Assessed to be Definitely, Probably, or Possibly Related to Protocol Treatment During the First Year.
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
This phase II trial is studying how well giving bevacizumab together with cisplatin, radiation therapy, and fluorouracil works in treating patients with stage IIB, stage III, stage IVA, or stage IVB nasopharyngeal cancer. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of nasopharyngeal cancer by blocking blood flow to the tumor. Drugs used in chemotherapy, such as cisplatin and fluorouracil, 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 bevacizumab together with chemotherapy and radiation therapy may kill more tumor cells.
Detailed Description
PRIMARY OBJECTIVES: I. Determine the safety and tolerability of bevacizumab and chemoradiotherapy comprising cisplatin and radiotherapy followed by adjuvant therapy comprising cisplatin, fluorouracil, and bevacizumab in patients with stage IIB-IVB nasopharyngeal cancer. SECONDARY OBJECTIVES: I. Determine the 1- and 2-year rates of locoregional progression-free in patients treated with this regimen. II. Determine the 1- and 2-year rates of distant metastases-free in patients treated with this regimen. III. Determine the 1- and 2-year rates of progression-free and overall survival of patients treated with this regimen. OUTLINE: This is a multicenter study. BEVACIZUMAB AND CHEMORADIOTHERAPY: Patients receive bevacizumab IV over 30-90 minutes and cisplatin IV over 20-30 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning in week 1, patients also undergo three-dimensional conformal radiotherapy or intensity-modulated radiotherapy once daily 5 days a week for a total of 33 fractions. ADJUVANT THERAPY: Beginning in week 10, patients receive fluorouracil IV continuously over 96 hours on days 1-4, cisplatin IV over 20-30 minutes on day 1 OR days 1 and 2, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed cancer of the nasopharynx based on biopsy of a primary lesion and/or lymph nodes
- •Histologic WHO types I-IIb/III
- •Stage IIB-IVB disease
- •No T1-2, N1 disease in which node positivity is based on the presence of retropharyngeal lymph nodes
- •No distant metastases
- •Zubrod performance status 0-1
- •WBC ? 4,000/mm?
- •Hemoglobin ? 9.0 g/dL
- •Platelet count ? 100,000/mm?
- •Absolute neutrophil count ? 1,500/mm?
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment (bevacizumab, cisplatin, fluorouracil, IMRT, 3D-CRT)
BEVACIZUMAB AND CHEMORADIOTHERAPY: Patients receive bevacizumab IV over 30-90 minutes and cisplatin IV over 20-30 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning in week 1, patients also undergo three-dimensional conformal radiotherapy or intensity-modulated radiotherapy once daily 5 days a week for a total of 33 fractions. ADJUVANT THERAPY: Beginning in week 10, patients receive fluorouracil IV continuously over 96 hours on days 1-4, cisplatin IV over 20-30 minutes on day 1 OR days 1 and 2, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Intervention: 3-Dimensional Conformal Radiation Therapy
Treatment (bevacizumab, cisplatin, fluorouracil, IMRT, 3D-CRT)
BEVACIZUMAB AND CHEMORADIOTHERAPY: Patients receive bevacizumab IV over 30-90 minutes and cisplatin IV over 20-30 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning in week 1, patients also undergo three-dimensional conformal radiotherapy or intensity-modulated radiotherapy once daily 5 days a week for a total of 33 fractions. ADJUVANT THERAPY: Beginning in week 10, patients receive fluorouracil IV continuously over 96 hours on days 1-4, cisplatin IV over 20-30 minutes on day 1 OR days 1 and 2, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Bevacizumab
Treatment (bevacizumab, cisplatin, fluorouracil, IMRT, 3D-CRT)
BEVACIZUMAB AND CHEMORADIOTHERAPY: Patients receive bevacizumab IV over 30-90 minutes and cisplatin IV over 20-30 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning in week 1, patients also undergo three-dimensional conformal radiotherapy or intensity-modulated radiotherapy once daily 5 days a week for a total of 33 fractions. ADJUVANT THERAPY: Beginning in week 10, patients receive fluorouracil IV continuously over 96 hours on days 1-4, cisplatin IV over 20-30 minutes on day 1 OR days 1 and 2, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Cisplatin
Treatment (bevacizumab, cisplatin, fluorouracil, IMRT, 3D-CRT)
BEVACIZUMAB AND CHEMORADIOTHERAPY: Patients receive bevacizumab IV over 30-90 minutes and cisplatin IV over 20-30 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning in week 1, patients also undergo three-dimensional conformal radiotherapy or intensity-modulated radiotherapy once daily 5 days a week for a total of 33 fractions. ADJUVANT THERAPY: Beginning in week 10, patients receive fluorouracil IV continuously over 96 hours on days 1-4, cisplatin IV over 20-30 minutes on day 1 OR days 1 and 2, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Fluorouracil
Treatment (bevacizumab, cisplatin, fluorouracil, IMRT, 3D-CRT)
BEVACIZUMAB AND CHEMORADIOTHERAPY: Patients receive bevacizumab IV over 30-90 minutes and cisplatin IV over 20-30 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning in week 1, patients also undergo three-dimensional conformal radiotherapy or intensity-modulated radiotherapy once daily 5 days a week for a total of 33 fractions. ADJUVANT THERAPY: Beginning in week 10, patients receive fluorouracil IV continuously over 96 hours on days 1-4, cisplatin IV over 20-30 minutes on day 1 OR days 1 and 2, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Intensity-Modulated Radiation Therapy
Outcomes
Primary Outcomes
Percentage of Patients With a Grade 4 Hemorrhage or Any Grade 5 Adverse Event Assessed to be Definitely, Probably, or Possibly Related to Protocol Treatment During the First Year.
Time Frame: From start of treatment to one year.
Estimated using a binomial distribution along with the 95% confidence interval. Adverse events (AE) are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.
Secondary Outcomes
- Percentage of Patients With Grade 4 Hemorrhage or Any Grade 5 Adverse Event Assessed to be Definitely, Probably, or Possibly Related to Protocol Treatment After the First Year.(Analysis occurs after all patients have been on study for at least 2 years. Patients are followed from day 366 to death or study termination whichever occurs first, up to 3.6 years.)
- Patient Tolerability to Each Component (Concurrent and Adjuvant) of the Protocol Treatment Regimen(From start of treatment to end of treatment (approximately day 109).)
- Death During or Within 30 Days of Discontinuation of Protocol Treatment.(From start of treatment to 30 days after end of treatment (treatment ends approximately day 109).)
- One- and Two-year Distant Metastases-free Rates(From registration to two years)
- One- and Two-year Loco-regional Progression-free Rates(Analysis occurs after all patients have been on study for at least 2 years. Patients are followed from study registration to death or study termination whichever occurs first, up to 3.6 years.)
- One- and Two-year Progression-free Survival Rates(Analysis occurs after all patients have been on study for at least 2 years. Patients are followed from study registration to death or study termination whichever occurs first, up to 3.6 years.)
- One- and Two-year Overall Survival Rates(Analysis occurs after all patients have been on study for at least 2 years. Patients are followed from study registration to death or study termination whichever occurs first, up to 3.6 years.)
- Percentage of Patients With Other Grade 3-5 Adverse Events Assessed to be Definitely, Probably, or Possibly Related to Protocol Treatment(Analysis occurs after all patients have been on study for at least 2 years. Patients are followed from start of treatment to death or study termination whichever occurs first, up to 3.6 years.)