Bevacizumab, Cisplatin, Radiation Therapy, and Fluorouracil in Treating Patients With Stage IIB, Stage III, Stage IVA, or Stage IVB Nasopharyngeal Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00408694
First received: December 6, 2006
Last updated: April 21, 2014
Last verified: October 2011

December 6, 2006
April 21, 2014
December 2006
December 2011   (final data collection date for primary outcome measure)
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. ] [ Designated as safety issue: Yes ]
Estimated using a binomial distribution along with their associated 95% confidence intervals. Graded using the CTCAE version 3.0.
Safety during year 1
Complete list of historical versions of study NCT00408694 on ClinicalTrials.gov Archive Site
  • Grade 4 Hemorrhage or Any Grade 5 Adverse Event Assessed to be Definitely, Probably, or Possibly Related to Protocol Treatment After the First Year. [ Time Frame: From day 366 to end of follow-up. ] [ Designated as safety issue: Yes ]
    Estimated using a binomial distribution along with their associated 95% confidence intervals. Graded using the CTCAE version 3.0.
  • Patient Tolerability to Each Component (Concurrent and Adjuvant) of the Protocol Treatment Regimen [ Time Frame: 109 From start of treatment to end of treatment (approximately day 109). ] [ Designated as safety issue: Yes ]
    Estimated using a binomial distribution along with their associated 95% confidence intervals. Evaluated in terms of protocol treatment delivery. Measured by the percentage of patients who received 2 or more cycles of cisplatin (CDDP) and bevacizumab (BV) during concurrent treatment with RT and RT scored by the study chair as no variation or minor variation. Tolerability for the adjuvant component will be measured by the percentage of patients who received 2 or more cycles of CDDP and 5-FU and BV during the adjuvant treatment phase.
  • Death During or Within 30 Days of Discontinuation of Protocol Treatment. [ Time Frame: From discontinuation of protocol treatment to 30 days after. ] [ Designated as safety issue: Yes ]
  • One- and Two-year Distant Metastases-free Rates [ Time Frame: From registration to two years. ] [ Designated as safety issue: No ]
    Estimated using the cumulative incidence method. Estimated along with their associated 95% confidence intervals.
  • One- and Two-year Loco-regional Progression-free Rates [ Time Frame: From registration to two years. ] [ Designated as safety issue: No ]
    Estimated using the cumulative incidence method. Estimated along with their associated 95% confidence intervals.
  • One- and Two-year Progression-free Survival Rates [ Time Frame: From registration to two years. ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method. Estimated along with their associated 95% confidence intervals.
  • One- and Two-year Overall Survival Rates [ Time Frame: From registration to two years. ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method. Estimated along with their associated 95% confidence intervals.
  • Safety after year 1
  • Patient tolerability to the treatment regimen
  • Toxicity
  • Death ≤ 30 days of discontinuation of protocol treatment
  • Distant metastases rates at 1 and 2 years
  • Locoregional progression rates at 1 and 2 years
  • Progression-free survival rates at 1 and 2 years
  • Second primary rates at 1 and 2 years
  • Overall survival rates at 1 and 2 years
Not Provided
Not Provided
 
Bevacizumab, Cisplatin, Radiation Therapy, and Fluorouracil in Treating Patients With Stage IIB, Stage III, Stage IVA, or Stage IVB Nasopharyngeal Cancer
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

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.

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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
  • Radiation: 3-dimensional conformal radiation therapy
    Undergo 3D-CRT
    Other Names:
    • 3D conformal radiation therapy
    • 3D-CRT
  • Radiation: intensity-modulated radiation therapy
    Undergo IMRT
    Other Name: IMRT
  • Biological: bevacizumab
    Given IV
    Other Names:
    • anti-VEGF humanized monoclonal antibody
    • anti-VEGF monoclonal antibody
    • Avastin
    • rhuMAb VEGF
  • Drug: cisplatin
    Given IV
    Other Names:
    • CACP
    • CDDP
    • CPDD
    • DDP
  • Drug: fluorouracil
    Given IV
    Other Names:
    • 5-fluorouracil
    • 5-Fluracil
    • 5-FU
Experimental: 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.

Interventions:
  • Radiation: 3-dimensional conformal radiation therapy
  • Radiation: intensity-modulated radiation therapy
  • Biological: bevacizumab
  • Drug: cisplatin
  • Drug: fluorouracil
Lee NY, Zhang Q, Pfister DG, Kim J, Garden AS, Mechalakos J, Hu K, Le QT, Colevas AD, Glisson BS, Chan AT, Ang KK. Addition of bevacizumab to standard chemoradiation for locoregionally advanced nasopharyngeal carcinoma (RTOG 0615): a phase 2 multi-institutional trial. Lancet Oncol. 2011 Dec 15; [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
46
December 2011
December 2011   (final data collection date for primary outcome measure)

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/mm³
  • Hemoglobin ≥ 9.0 g/dL
  • Platelet count ≥ 100,000/mm³
  • Absolute neutrophil count ≥ 1,500/mm³
  • INR ≤ 1.5
  • aPTT ≤ 1.5 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 1.5 times ULN
  • ALT and AST ≤ 1.5 times ULN
  • Bilirubin ≤ 1.5 times ULN
  • Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 55 mL/min
  • Urine protein:creatinine (UPC) ratio < 1.0

    • If UPC > 0.5, 24-hour urine protein must be < 1,000 mg
  • Hearing loss primarily sensorineural in nature and requiring a hearing aid or intervention that interferes in a clinically significant way with activities of daily living allowed
  • Conductive hearing loss from tumor-related otitis media is allowed
  • No severe, active comorbidity, including any of the following:

    • Ongoing bleeding diathesis, hemorrhagic disorder, or coagulopathy within the past 6 months
    • Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
    • Esophageal varices, nonhealing wound, nonhealing ulcer, or bone fracture within the past 6 months
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within the past 30 days
    • Unstable angina and/or congestive heart failure or peripheral vascular disease requiring hospitalization within the past 12 months
    • Major medical or psychiatric illness that, in the opinion of the study investigator, would preclude study compliance
    • Active, untreated infection and/or acute bacterial or fungal infection requiring intravenous antibiotics
    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
    • History of significant weight loss (> 15% from baseline)
    • History of arterial thromboembolic events
    • Acquired immune deficiency syndrome
    • Transmural myocardial infarction
    • Cerebrovascular accident
    • Transient ischemic attack
    • Any other cardiac condition that, in the opinion of the investigator, would preclude study compliance
  • No gross hemoptysis or hematemesis, defined as bright red blood of ≥ 1 teaspoon per coughing episode, within the last 4 weeks (incidental blood mixed with phlegm allowed)
  • No other invasive malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the breast, oral cavity, or cervix
  • Nutritional and physical condition considered suitable for study treatment
  • No significant traumatic injury within the past 4 weeks
  • No history of allergic reaction to the study drugs
  • No baseline blood pressure > 150/100 mm Hg
  • No peripheral neuropathy ≥ grade 2
  • Not pregnant or nursing
  • Negative serum pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment
  • At least 10 days since prior and no concurrent dipyridamole, ticlopidine, clopidogrel bisulfate, cilostazol, warfarin, heparin, daily treatment with acetylsalicylic acid (> 325 mg/day), or nonsteroidal anti-inflammatory medications known to inhibit platelet function
  • No prior head and neck surgery of the primary tumor or lymph nodes except for incisional or excisional biopsies

    • More than 15 days since prior biopsies
  • More than 1 week since prior fine-needle aspirations or placement of percutaneous gastrostomy tube
  • More than 4 weeks since prior major surgical procedures
  • No prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
  • No prior bevacizumab or other vascular endothelial growth factor-targeting agents
  • No prior systemic chemotherapy for the study cancer

    • Prior chemotherapy for a different cancer allowed
  • No concurrent hematologic growth factors (e.g. filgrastim [G-CSF], darbepoetin alfa, epoetin alfa) during study chemoradiotherapy
  • No concurrent prophylactic growth factors for neutropenia during study adjuvant therapy
  • No concurrent prophylactic amifostine or pilocarpine
  • No other concurrent experimental therapeutic cancer treatments
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT00408694
NCI-2009-00736, NCI-2009-00736, RTOG-0615, CDR0000518526, RTOG 0615, RTOG-0615, U10CA021661
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Nancy Lee Radiation Therapy Oncology Group
National Cancer Institute (NCI)
October 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP