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

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

Conditions: Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IV Nasopharyngeal Undifferentiated Carcinoma AJCC v7; Stage II Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage III Nasopharyngeal Undifferentiated Carcinoma AJCC v7; Stage III Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7

Treatments: Radiation: 3-Dimensional Conformal Radiation Therapy; Radiation: Intensity-Modulated Radiation Therapy; Drug: Fluorouracil; Biological: Bevacizumab; Drug: Cisplatin

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00408694

RTOG-0615

NCI-2009-00736 (Registry Identifier)

CDR0000518526

U10CA021661 (U.S. NIH Grant/Contract)

RTOG 0615 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 46 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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?

• 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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46 participants in 1 patient group

Treatment (bevacizumab, cisplatin, fluorouracil, IMRT, 3D-CRT)

Experimental group

Description:

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.

Treatment:

Drug: Cisplatin

Biological: Bevacizumab

Drug: Fluorouracil

Radiation: Intensity-Modulated Radiation Therapy

Radiation: 3-Dimensional Conformal Radiation Therapy