Study of Pazopanib and Ixabepilone in Patients With Solid Tumors
Condition: Breast Cancer; Lung Cancer; Colon Cancer; Pancreatic Cancer; Head and Neck Cancer; Kidney Cancer; Sarcoma; Hepatocellular Cancer
MeSH terms: Pancreatic Neoplasms; Sarcoma; Head and Neck Neoplasms; Colonic Neoplasms; Kidney Neoplasms; Carcinoma, Renal Cell; Liver Neoplasms; Carcinoma, Hepatocellular
Intervention: Pazopanib; Ixabepilone
Intervention description: Escalating doses 400-800 mg by mouth once daily beginning day 1 and continuing.; Escalating doses 25-32 mg/m2 by intravenous infusion on day 1 of each 21 day cycle
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Solid tumor malignancy; breast cancer; lung cancer; colon cancer; pancreatic cancer; head and neck cancer; kidney cancer; sarcoma; hepatocellular cancer

Summary:

      This is a Phase I study; dose escalating the combination of pazopanib when taken daily and
      ixabepilone when administered on day 1 of a 3 week treatment course.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of advanced non-hematologic solid tumor malignancy, including, but not
             limited to breast, lung, colon, pancreatic, head and neck, kidney or sarcoma that has
             failed or become intolerant to standard therapy and is no longer likely to respond to
             such therapy Effective with the August 2011 version of the protocol, enrollment is
             limited to squamous cell carcinoma of the head and neck (refer to section 1.4 for
             rationale). Note: Patients with a primary diagnosis of hepatocellular carcinoma will
             be eligible for enrollment into dose level 1 or 2 only, provided they met all other
             inclusion/exclusion criteria - the maximum tolerated dose (MTD) for pazopanib
             monotherapy in patients with hepatocellular cancer was found to be 600 mg daily.

          -  Measureable or evaluable disease per Response Evaluation Criteria in Solid Tumors
             (RECIST).

          -  Prior systemic chemotherapy, immunotherapy, or biological therapy is allowed; however
             prior use of either pazopanib or ixabepilone alone or in combination is not allowed.

          -  At least 14 days must have elapsed since 1) previous systemic therapy (28 days for
             bevacizumab) before the 1st dose of study drug, 2) last dose of radiation therapy or
             surgery (28 days for major surgery).

          -  Patient must have recovered from the acute toxic effects of previous anti-cancer
             treatment prior to study enrollment.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

          -  Adequate organ function within 14 days of enrollment defined as:

               -  Absolute neutrophil count (ANC) >1.5 x 10^9/L

               -  Hemoglobin > or = 9 g/dL

               -  Platelets > or = 100 x 10^9/L

               -  Prothrombin time or international normalized ratio, and partial thromboplastin
                  time (PTT) < or = 1.2 x upper limit of normal (ULN)

               -  Total bilirubin < or = ULN

               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < or = 2.5 x
                  ULN

               -  Serum creatinine < or = 1.5 mg/dL

               -  Urine protein to Creatinine Ratio < 1

               -  Total serum calcium < 12.0 mg/dL

          -  Men and women with child-bearing potential must adhere to protocol criteria to prevent
             conception during study

        Exclusion Criteria:

          -  Women who are pregnant or nursing.

          -  Prior radiation to > =or = 30% of major bone marrow containing areas (pelvis, lumbar
             spine)

          -  History or clinical evidence of central nervous system (CNS) metastases or
             leptomeningeal carcinomatosis

          -  Clinically significant gastrointestinal abnormalities that may increase the risk of GI
             bleeding or may affect absorption of investigational product

          -  History of another malignancy - must be at least 3 years disease-free

          -  Presence of uncontrolled infection

          -  Prolongation of corrected QT interval (QTc) > 480 msecs

          -  History of any one or more of the following cardiovascular conditions within the past
             6 months:

               -  Cardiac angioplasty or stenting

               -  Myocardial infarction

               -  Unstable angina

               -  Coronary artery bypass graft surgery

               -  Symptomatic peripheral vascular disease

               -  Class III or IV congestive heart failure, as defined by the New York Heart
                  Association (NYHA)

          -  Poorly controlled hypertension

          -  History of cerebrovascular accident,pulmonary embolism or untreated deep venous
             thrombosis (DVT) within the past 6 months

          -  Prior major surgery or trauma within 28 days prior to 1st dose of study drug

          -  Evidence of active bleeding or bleeding diathesis

          -  Known endobronchial lesions or involvement of large pulmonary vessels by tumor

          -  Hemoptysis with 6 weeks of 1st dose of study drug

          -  Neuropathy Grade 1