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A Phase II Study of Pazopanib in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Refractory to Platinum-Based Chemotherapy

Phase 2
18 Years
70 Years
Open (Enrolling)
Head and Neck Squamous Cell Carcinoma

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Trial Information

A Phase II Study of Pazopanib in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Refractory to Platinum-Based Chemotherapy

Pazopanib, a tyrosine kinase inhibitor targets VEGFR1/2/3, PDGFR alpha & beta, c-KIT, and
FGFR1/3 to inhibit angiogenesis. The phase II trial in advanced RCC (previous cytokine
therapy in 25 % of patients) yielded good clinical benefits (response rate 34.6%; disease
control 79.8%) with durable activity (progression-free to near 1 year) and acceptable
toxicity. The randomized phase III trial in advanced RCC are ongoing and interim analysis
revealed prolonged progression-free survival in pazopanib group compared with placebo group.
Pazopanib is an active multi-targeted tyrosine kinase inhibitor needed to broaden it new
indications to treat cancers. VEGF-C and FGF pathways are also important in the
angiogenesis, metastasis, invasion, and cancer stem cell renewal in HNSCC. Pazopanib can
also inhibit these two pathways and might offer much more suppression on tumor angiogenesis
and growth in HNSCC compared with sunitinib. Common side effects of pazopanib are grade I to
II diarrhea, hypertension, hair color change, and nausea, which are all manageable. Because
of the advantageous activity against VEGF-C and FGF pathways and favorable toxicity profile
comparing with sunitinib, we plan this phase II trial of pazopanib in cisplatin-refractory
recurrent or metastatic HNSCC.

Serum inflammation markers, like IL-6 (esp. in inflammation- mediated cancers, like virus-
related hepatocellular carcinoma and HNSCC), and host/tumor VEGF/VEGFR2 polymorphism
attracted much attention in tumor angiogenesis dependence and response prediction of
anti-angiogenesis treatments, in addition to previously described sVEGFR2 and circulating
endothelial progenitors(CEP) in the phase II trial of RCC. We will study serum
IL-6/VEGF/sVEGFR2/CEP and host/tumor VEGF/VEGFR2 polymorphism for prognosis and response

Inclusion Criteria:

1. Histologically confirmed HNSCC.

2. Recurrent or metastatic setting, refractory to previous cisplatin or
carboplatin-based chemotherapy.

3. At least one measurable lesion (according to RECIST v 1.1 criteria).

4. Eastern Cooperative Oncology Group performance status 0 to 2.

5. Age>18y/o,<=70y/o.

6. Adequate bone marrow, hepatic, and renal functions as evidenced by the following:

- Absolute neutrophil count>=1,500 cells/L, platelet count>=100,000 cells/L, and
hemoglobin>=9 g/dL.

- Total bilirubin<=1.5 X ULN, AST/ALT<=3.0 X ULN

- Creatinine<=1.5 mg/dL.

7. Informed consent, obtained in writing.

Exclusion Criteria:

1. Second malignancy.

2. Locoregional recurrence amenable to definite surgery or radiation again.

3. Brain/meningeal metastasis with IICP or bone metastasis with spinal cord compression.

4. Pregnancy or nursing women.

5. Having received more than two prior lines of intravenous chemotherapy in the
palliative setting.

6. Having received antiangiogenesis agent in the palliative setting.

7. Having received chemotherapy or radiation therapy or surgery within 3 weeks.

8. Major systemic diseases those are inappropriate for systemic chemotherapy according
to clinician's professional judgment.

9. Mental status not fit for clinical trials.

10. Clinically significant gastrointestinal abnormalities that may increase the risk for
gastrointestinal bleeding including, but not limited to:

- Active peptic ulcer disease

- Known intraluminal metastatic lesion/s with risk of bleeding

- Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other
gastrointestinal conditions with increased risk of perforation

- History of abdominal fistula, gastrointestinal perforation, or intra abdominal
abscess within 28 days prior to beginning study treatment.

11. Corrected QT interval (QTc)>480 msecs using Bazett's formula.

12. Poorly controlled hypertension defined as SBP>=140 mmHg or DBP>=90mmHg

13. Concomitant diseases that might be aggravated by investigational drugs:

- Active or non-controlled infection.

- Severe upper gastrointestinal bleeding.

- History of any one or more of the following cardiovascular conditions within the
past 12 months:

- Cardiac angioplasty or stenting,

- Myocardial infarction,

- Unstable angina,

- Symptomatic peripheral vascular disease,

- Class III or IV congestive heart failure, as defined by the New York Heart
Association (NYHA)

14. Hemoptysis within 6 weeks of first dose of Pazopanib, prior major surgery within 4
weeks of first dose of Pazopanib, or presence of any non-healing wound/fracture.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective response rate

Outcome Description:

Evaluable for response: From the RECIST 1.1 paper,all patients included in the study must be accounted for in the results, even if there are major protocol treatment deviations or if they are not evaluable.

Outcome Time Frame:

1 year

Safety Issue:


Principal Investigator

Ruey-Long Hong, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Taiwan University Hospital


Taiwan: Department of Health

Study ID:




Start Date:

June 2011

Completion Date:

May 2014

Related Keywords:

  • Head and Neck Squamous Cell Carcinoma
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Head and Neck Neoplasms