NEXT: Subsequent Exposure to Tyrosine Kinase Inhibition at Recurrence After Adjuvant Therapy in Renal Cell Carcinoma
Condition: Renal Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Renal Cell; Recurrence
Intervention: Axitinib
Intervention description: Axitinib 5 mg orally with food every 12 hours. One cycle=28 days.
Intervention MeSH terms: Axitinib; Tyrosine Protein Kinase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: RCC; Clear Cell Renal Cell Carcinoma; ccRCC; Metastatic RCC; Recurrent RCC; Kidney Cancer; Kidney Neoplasms; Axitinib; AG-013736; Tyrosine Kinase Inhibition; TKI

Summary:

      The purpose of this study is to see how well the study drug, axitinib, helps control renal
      (kidney) cancer that has come back (recurrent) or spread (metastatic). Patients must have
      already been treated as a participant in a clinical trial with sunitinib, sorafenib,
      pazopanib or placebo (sugar pill) after their initial surgery.

      This study will examine the effect of adjuvant tyrosine kinase inhibition (TKI) therapy
      (sorafenib, sunitinib or pazopanib) on subsequent exposure to TKI with axitinib in the
      first-line recurrent or metastatic setting.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Locally recurrent or metastatic RCC requiring systemic therapy following treatment
             (tx) with sorafenib, sunitinib, pazopanib, or placebo on an adjuvant study

          -  Required to have primary or recurrence tumor samples containing clear cell variant RCC
             with <50% of any other histology

          -  Recurrence must occur ≥ 3 months following end of exposure to the adjuvant
             intervention

          -  Received ≥ 3 six week cycles of prior adjuvant tx with sorafenib, sunitinib, pazopanib
             or placebo in the adjuvant setting on a clinical trial, or recurrence >3 months of tx
             on an adjuvant placebo arm

          -  Required to have measurable recurrent or metastatic disease that is not curable by
             standard radiation therapy or surgery

          -  Male or female, ≥ 18 years old

          -  ECOG PS 0 or 1

          -  Blood pressure (B/P) must be controlled at time of enrollment. Tx with
             antihypertensive medication(s) is allowed. Controlled B/P is defined as in clinic
             measurement of systolic B/P ≤ 140 mm Hg AND diastolic B/P ≤ 90 mm Hg. If B/P is
             uncontrolled at time of planned enrollment, tx or optimization with antihypertensive
             medication(s) may be initiated in order to control B/P. Patient may be considered for
             enrollment when this has happened.

          -  Women must not be pregnant or breastfeeding

          -  Men and women who are of reproductive potential must be willing to employ an effective
             method of birth control/contraception

          -  Willingness and ability to comply with scheduled visits, tx plans, laboratory tests,
             and other study procedures

          -  Ability to understand and willingness to sign an IRB-approved informed consent

          -  Adequate organ function as evidenced by the following, obtained within 28 days prior
             to registration:

               -  Absolute neutrophil count (ANC) ≥ 1250 cells/mm³

               -  Platelet count ≥ 75,000 cells/mm³

               -  Hemoglobin ≥ 9.0 g/dL

               -  Total direct serum bilirubin ≤ 1.5x upper limit of normal (ULN)

               -  ALT and AST ≤ 2.5 x ULN unless there are liver metastases in which case AST and
                  ALT ≤ 5.0 x ULN

               -  Serum creatinine <1.5 x ULN or calculated creatinine clearance ≥ 45 mL/min

               -  Urine protein <2+ by urine dipstick

          -  Resolution of all previous tx-related toxicity to ≤ grade 1 or back to baseline

          -  No major surgery <4 weeks or radiation therapy <2 weeks of starting study tx. Prior
             palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at
             least one measurable lesion that has not been irradiated.

          -  No clinically significant gastrointestinal abnormalities

          -  No current use or anticipated need for tx with drugs that are known potent CYP3A4
             inhibitors

          -  No current or anticipated need for tx with drugs that are known CYP3A4 or CYP1A2
             inducers

          -  No current requirement of anticoagulant therapy with oral vitamin K antagonists

          -  No untreated brain metastases, spinal cord compression, or carcinomatous meningitis.
             Patients must be off oral (systemic) steroids prior to registration. Inhalational
             steroids, e.g., for asthma, emphysema are permissible.

          -  No serious uncontrolled medical disorder or active infection that would impair their
             ability to receive study tx

          -  None of the following conditions within the 6 months prior to study drug: myocardial
             infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic
             congestive heart failure, cerebrovascular accident, transient ischemic attack, deep
             vein thrombosis or pulmonary embolism

          -  No known HIV or AIDS-related illness

          -  No other active malignancy

          -  No dementia or significantly altered mental status that would prohibit the
             understanding or rendering of informed consent and compliance with the requirements of
             the protocol

          -  No other severe acute/chronic medical or psychiatric condition or lab abnormality that
             may increase the risk associated with study participation or study drug administration
             or may interfere with the interpretation of study results, and in the judgment of the
             investigator would make the patient inappropriate for entry into this study