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

Primary Purpose

Head and Neck Squamous Cell Carcinoma

Status

Unknown status

Phase

Phase 2

Locations

Taiwan

Study Type

Interventional

Intervention

Pazopanib

About this trial

This is an interventional treatment trial for Head and Neck Squamous Cell Carcinoma

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Histologically confirmed HNSCC.
Recurrent or metastatic setting, refractory to previous cisplatin or carboplatin-based chemotherapy.
At least one measurable lesion (according to RECIST v 1.1 criteria).
Eastern Cooperative Oncology Group performance status 0 to 2.
Age>18y/o,<=70y/o.
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.
Informed consent, obtained in writing.

Exclusion Criteria:

Second malignancy.
Locoregional recurrence amenable to definite surgery or radiation again.
Brain/meningeal metastasis with IICP or bone metastasis with spinal cord compression.
Pregnancy or nursing women.
Having received more than two prior lines of intravenous chemotherapy in the palliative setting.
Having received antiangiogenesis agent in the palliative setting.
Having received chemotherapy or radiation therapy or surgery within 3 weeks.
Major systemic diseases those are inappropriate for systemic chemotherapy according to clinician's professional judgment.
Mental status not fit for clinical trials.
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.
Corrected QT interval (QTc)>480 msecs using Bazett's formula.
Poorly controlled hypertension defined as SBP>=140 mmHg or DBP>=90mmHg
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)
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.

Sites / Locations

National Taiwan University HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pazopanib

Arm Description

Single arm study, pazopanib

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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%)

progression-free survival

overall survival

Full Information

NCT ID

NCT01377298

First Posted

May 16, 2011

Last Updated

June 20, 2011

Sponsor

National Taiwan University Hospital

Collaborators

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT01377298

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2011

Overall Recruitment Status

Unknown status

Study Start Date

June 2011 (undefined)

Primary Completion Date

May 2013 (Anticipated)

Study Completion Date

May 2014 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor

National Taiwan University Hospital

Collaborators

GlaxoSmithKline

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Head and Neck Squamous Cell Carcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

45 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Pazopanib

Arm Type

Experimental

Arm Description

Single arm study, pazopanib

Intervention Type

Drug

Intervention Name(s)

Pazopanib

Intervention Description

200mg/tablet, 800mg/day PO.

Primary Outcome Measure Information:

Title

Objective response rate

Description

Time Frame

1 year

Secondary Outcome Measure Information:

Title

disease control rate (CR+PR+SD),

Description

Time Frame

1 year

Title

Tumor Necrosis Ratio

Description

Time Frame

1 year

Title

progression-free survival

Time Frame

1 year

Title

overall survival

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Histologically confirmed HNSCC. Recurrent or metastatic setting, refractory to previous cisplatin or carboplatin-based chemotherapy. At least one measurable lesion (according to RECIST v 1.1 criteria). Eastern Cooperative Oncology Group performance status 0 to 2. Age>18y/o,<=70y/o. 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. Informed consent, obtained in writing. Exclusion Criteria: Second malignancy. Locoregional recurrence amenable to definite surgery or radiation again. Brain/meningeal metastasis with IICP or bone metastasis with spinal cord compression. Pregnancy or nursing women. Having received more than two prior lines of intravenous chemotherapy in the palliative setting. Having received antiangiogenesis agent in the palliative setting. Having received chemotherapy or radiation therapy or surgery within 3 weeks. Major systemic diseases those are inappropriate for systemic chemotherapy according to clinician's professional judgment. Mental status not fit for clinical trials. 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. Corrected QT interval (QTc)>480 msecs using Bazett's formula. Poorly controlled hypertension defined as SBP>=140 mmHg or DBP>=90mmHg 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) 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Ruey-Long Hong, MD

Phone

+886 2 23123456

Ext

67510

rlhong@ntu.edu.tw

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ruey-Long Hong, MD

Organizational Affiliation

National Taiwan University Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

National Taiwan University Hospital

City

Taipei

ZIP/Postal Code

100

Country

Taiwan

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ruey-Long Hong, MD

Phone

+886 2 23123456

Ext

67510

rlhong@ntu.edu.tw

First Name & Middle Initial & Last Name & Degree

Jo-Pai Chen, MD

First Name & Middle Initial & Last Name & Degree

Ruey-Long Hong, MD

12. IPD Sharing Statement

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

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