Neoadjuvant Pazopanib in Renal Cell Carcinoma
Condition: Renal Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: Pazopanib
Intervention description: 800 mg orally once daily for 8 weeks, prior to nephrectomy
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Renal Cell Carcinoma; RCC; Votrient; Pazopanib; Nephrectomy; Neoadjuvant; Phase II; LCCC 1028; Lineberger Comprehensive Cancer Center

Summary:

      This study will be a single arm phase II clinical trial of 8 weeks of daily, oral
      neo-adjuvant pazopanib prior to nephrectomy in 39 evaluable patients with histologically
      confirmed localized renal cell carcinoma (RCC).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥ 18 years with radiographic evidence of nonmetastatic renal cell carcinoma

          -  Histological verification of clear cell renal cell carcinoma (-Clinical stage 2 (7 cm)
             or greater with localized disease

          -  No evidence of extranodal metastatic disease

          -  Appropriate candidate for surgery

          -  The Eastern Cooperative Oncology Group (ECOG) Performance status of 0-1

          -  Adequate organ function

          -  Serum calcium, magnesium, potassium within normal limits, or if outside of normal
             limits, must be deemed clinically insignificant by the Investigator.

          -  No known coagulopathy

          -  Ability to read and follow instructions

          -  Women of childbearing potential must have a negative serum pregnancy test performed
             within 14 days prior to the start of pazopanib treatment and both men and women must
             be willing to use adequate contraception.

          -  Able to provide written, informed consent

          -  Blood and urine samples must be provided from all subjects for biomarker analysis
             before and during treatment with pazopanib

        Exclusion Criteria

          -  Known or suspected allergy to pazopanib

          -  Inability to swallow or retain oral medication

          -  Prior malignancy Exception: Subjects who have had another malignancy and have been
             disease-free for three years, or subjects with a history of completely resected
             non-melanomatous skin carcinoma or successfully treated in situ carcinoma are
             eligible.

          -  Unable or unwilling to discontinue use of prohibited medications at least 7 days prior
             to the first dose of study drug and for the duration of the study.

          -  Clinically significant gastrointestinal abnormalities that may increase the risk for
             gastrointestinal bleeding including

          -  History of cerebrovascular accident including transient ischemic attack (TIA),
             pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.

          -  History of any one or more cardiovascular conditions within the past 6 months

          -  Hypertension [defined as systolic blood pressure (SBP) of ≥140 mmHg OR diastolic blood
             pressure (DBP) of ≥ 90 mmHg in spite of optimal medical management.

          -  Evidence of active bleeding or bleeding diathesis.

          -  Any serious and/or unstable pre-existing medical (especially hepatic disease),
             psychiatric, or other condition that could interfere with subject's safety, provision
             of informed consent, or compliance to study procedures.

          -  Prior major surgery or trauma within 28 days prior to first dose of pazopanib and/or
             presence of any non-healing wound, fracture, or ulcer (procedures such as catheter
             placement not considered to be major).

          -  Pregnant or breastfeeding; breastfeeding may not resume for 14 days after the last
             dose of pazopanib

          -  Prior treatment with any of the following anti-cancer therapies for treatment of their
             RCC:

               -  radiation therapy, surgery or tumor embolization

               -  chemotherapy, immunotherapy, biologic therapy, investigational therapy or
                  hormonal therapy

          -  Baseline Corrected QT Interval (QTc) >480 msec or other clinically significant
             baseline ECG abnormality