Clinical Trials

Text Size A A

E-Mail to a Friend






secret  Click to Play Audio


Sarcoma

Pazopanib Hydrochloride Followed By Chemotherapy and Surgery for Soft Tissue Sarcoma
The Effect of Antiangiogenic Therapy With Pazopanib Prior to Preoperative Chemotherapy for Subjects With Extremity Soft Tissue Sarcomas: A Randomized Study to Evaluate Response by Imaging
Status Conditions Phase Study ID
Recruiting Soft tissue sarcoma Phase II NCT01446809
Summary

This randomized pilot clinical trial studies pazopanib hydrochloride followed by chemotherapy and surgery in treating patients with soft tissue sarcoma. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes that are needed for cell growth and may also stop the growth of soft tissue sarcoma by blocking blood flow to the tumor. Giving pazopanib hydrochloride and chemotherapy before surgery may make the tumor smaller and reduce the amount of tissue that needs to be removed.


Investigator
Robin L. Jones, MD
Location    
Seattle Cancer Care Alliance 800-804-8824  
Eligibility Criteria (must meet the following to participate in this study)
  • Histologically or cytologically confirmed soft-tissue sarcoma, excluding rhabdomyosarcoma, adipocytic sarcomas, Ewing's, osteosarcoma, or gastrointestinal stromal tumor; American Joint Committee on Cancer (AJCC) (6th Edition) Stage III or T2a Stage II or Stage IV treatment naive patients planned for resection of the primary tumor, with resectable metastatic disease
  • Measurable disease greater than 5 centimeters in greatest dimension; measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter for non-nodal lesions and short axis for nodal lesions to be recorded) by chest x-ray, computed tomography (CT) scan, magnetic resonance imaging (MRI) or with calipers by clinical exam; all tumor measurements must be recorded in millimeters (or decimal fractions of centimeters)
  • Intermediate or high grade lesions: 2 or 3 on a scale of 1-3 or grades 2 to 4 on a scale of 1-4
  • Sarcoma located on upper (includes shoulder) or lower (includes hip) extremities or on the body wall
  • Life expectancy of greater than 6 months
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1
  • Karnofsky >= 80%
  • No prior chemotherapy, radiotherapy, or antiangiogenic therapy
  • Absolute neutrophil count (ANC) >= 1500 /uL
  • Hemoglobin (Hgb) >= 9.0 g/dL
  • Platelets >= 100,000/uL
  • Creatinine =< 1.5 x upper limit of normal (ULN)
  • Bilirubin =< 1.5 mg/dL
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 1.5 x ULN
  • Prothrombin time (PT)/international normalized ratio(INR)/partial thromboplastin time (PTT) within 1.2 X the ULN unless a subject is receiving Coumadin and has stable INR which is in range for the desired level of anticoagulation
  • Left ventricular ejection fraction (LVEF) >= 50%
  • Blood pressure (BP) no greater than 140 mmHg (systolic) and 90 mmHg (diastolic) for eligibility; initiation or adjustment of BP medication is permitted prior to study entry provided that the average of three BP readings at a visit prior to enrollment is less than 140/90 mmHg
  • Eligibility of subjects receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of pazopanib will be determined following review of their cases by the Principal Investigator
  • Women of child-bearing potential and men must agree to use adequate contraception
  • A female is eligible to enter and participate in this study if she is of non-childbearing potential (i.e., physiologically incapable of becoming pregnant) or if she is of childbearing potential
  • Ability to understand and the willingness to sign a written informed consent document
Exclusions (conditions that would prevent participation in this study)
  • Subjects with known brain metastases and/or unresectable sarcoma
  • Uncontrolled intercurrent illness including, active serious infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac ventricular arrhythmia requiring anti-arrhythmic therapy, or psychiatric illness/social situations that would limit compliance with study
  • Pregnant or lactating women
  • Subjects with a currently active second malignancy other than non-melanoma skin cancers
  • Subjects may not be receiving other investigational agents
  • Subjects with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to pazopanib or other agents used in the study are excluded
  • Subjects who have both bilirubin > ULN and AST/ALT > ULN are ineligible
  • Subjects with a urine protein/creatinine ratio greater than 1
  • Subjects with a baseline QTc of equal to or greater than 480 msecs or other significant electrocardiogram (ECG) abnormalities are ineligible
  • Certain medications that act through the cytochrome P450 (CYP450) system are specifically prohibited in subjects receiving pazopanib and others should be avoided or administered with extreme caution
  • Strong inhibitors of CYP3A4 such as ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinivir, retonavir, saquinavir, telithromycin, voriconazole may increase pazopanib concentrations and are prohibited; grapefruit juice is also an inhibitor of CYP450 and should not be taken with pazopanib
  • Strong inducers of CYP3A4, such as rifampin, may decrease pazopanib concentrations, are prohibited
  • Medications which have narrow therapeutic windows and are substrates of CYP3A4, CYP2D6, or CYP2C8 should be avoided and, if necessary, administered with caution
  • Pazopanib, 800 mg once daily, has no effect on CYP2C9, CYP1A2, or CYP2C19 in vivo but does in vitro; therefore, therapeutic doses of warfarin, a substrate of CYP2C9, and omeprazole, a substrate of CYP2C19 are permitted; caffeine, a substrate of CYP1A2, is also permitted
  • Certain medications that are associated with a risk for QTc prolongation and/or Torsades de Pointes, although not prohibited, should be avoided or replaced with medications that do not carry these risks, if possible
  • Subjects who require heparin other than low-molecular weight heparin
  • Subjects with any condition that may impair the ability to swallow or absorb oral medications/investigational product including:
  • Any lesion, whether induced by tumor, radiation or other conditions, which makes it difficult to swallow capsules or pills
  • Prior surgical procedures affecting absorption including, but not limited to major resection of stomach or small bowel
  • Active peptic ulcer disease
  • Malabsorption syndrome
  • Subjects with any condition that may increase the risk of gastrointestinal bleeding or gastrointestinal perforation, including
  • Active peptic ulcer disease
  • Known intraluminal metastatic lesions
  • Inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease) or other gastrointestinal conditions which increase the risk of perforation
  • History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days prior to beginning study treatment
  • Subjects with any of the following cardiovascular conditions within the past 6 months:
  • Cerebrovascular accident (CVA) or transient ischemic attack (TIA)
  • Cardiac arrhythmia
  • Admission for unstable angina
  • Cardiac angioplasty or stenting
  • Coronary artery bypass graft surgery
  • Pulmonary embolism, untreated deep venous thrombosis (DVT) or DVT which has been treated with therapeutic anticoagulation for less than 6 weeks
  • Arterial thrombosis
  • Symptomatic peripheral vascular disease
  • Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system; a subject who has a history of Class II heart failure and is asymptomatic on treatment may be considered eligible
  • History of hemoptysis in excess of 2.5 mL (1/2 teaspoon ) within 8 weeks prior to first dose of study drug
  • History of serious or non-healing wound, ulcer, or bone fracture
  • Human immunodeficiency virus (HIV)-positive subjects on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with pazopanib
Last Updated
November 07, 2012
See this trial at ClinicalTrials.gov
Access protocol and consent forms at Fred Hutchinson Cancer Research Center
Disclaimer: We update this information regularly. However, what you read today may not be completely up to date.

Please remember:
  • Talk to your health care providers first before making decisions about your health care.
  • Whether you are eligible for a research study depends on many things. There are specific requirements to be in research studies. These requirements are different for each study.