Pazopanib in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

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

Because of the advantageous activity against VEGF-C and FGF pathways and favorable toxicity profile comparing with sunitinib, the investigators plan this phase II trial of pazopanib in cisplatin-refractory recurrent or metastatic HNSCC.

Study Overview

• Status: Unknown
• Conditions: Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Pazopanib

Detailed Description

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 correlation.

• Study Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Ruey-Long Hong, MD; Phone Number: 67510 +886 2 23123456; Email: rlhong@ntu.edu.tw
    • Sub-Investigator: Jo-Pai Chen, MD
    • Principal Investigator: Ruey-Long Hong, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pazopanib; Single arm study, pazopanib	Drug: Pazopanib; 200mg/tablet, 800mg/day PO.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	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.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival		1 year
progression-free survival		1 year
disease control rate (CR+PR+SD),	Patients who receive at least 3 days of pazopanib will be included in the baseline, dosing and safety summaries. The primary calculation of complete response rate will be based on all response-evaluable patients.	1 year
Tumor Necrosis Ratio	Tumor Necrosis Ratio: On contrast enhanced T1WI, (CE-T1WI), manual delineation of the area of necrosis and entire tumor is performed on the central tumor-containing slice with the areas of necrotic center and entire tumor automatically generated. The tumor necrosis ratio is defined as the area of necrotic center over that of the entire tumor. (<25%, <50%, <75%, or >75%)	1 year

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: Ruey-Long Hong, MD, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Anticipated): May 1, 2013
• Study Completion (Anticipated): May 1, 2014

Study Registration Dates

• First Submitted: May 16, 2011
• First Submitted That Met QC Criteria: June 20, 2011
• First Posted (Estimate): June 21, 2011

Study Record Updates

• Last Update Posted (Estimate): June 21, 2011
• Last Update Submitted That Met QC Criteria: June 20, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: 201007042M