A Study to Compare Treatments for a Type of Kidney Cancer called TFE/Translocation Renal Cell Carcinoma (tRCC)
12 Months and older, Male and Female
This phase II trial studies how well axitinib and nivolumab work in treating patients with TFE/translocation renal cell carcinoma that cannot be removed by surgery (unresectable) or has spread to other places in the body (metastatic). Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving axitinib and nivolumab may work better in treating patients with TFE/translocation renal cell carcinoma compared to standard treatment, including surgery, chemotherapy, or immunotherapy.
I. To establish the clinical activity, assessed primarily by progression-free survival, of nivolumab therapy with or without axitinib for advanced transcription factor E3/translocation morphology renal cell carcinoma (TFE/tRCC).
I. To further define the toxicities of the study arms in the treatment of translocation morphology RCC across all ages.
I. To characterize tRCC clinical behavior across all age groups.
II. To evaluate type of antitumor immune response and stability of T cell activation before and after treatment with immunotherapy or antiangiogenic therapy.
III. To develop a tumor bank of tRCC tumor samples treated on study for further biological investigations.
IV. To characterize the pharmacokinetics of axitinib when given in combination with nivolumab in pediatric patients with tRCC.
OUTLINE: Patients are now randomized to 1 of 2 arms - Arm A or Arm C.
ARM A: Patients receive axitinib orally (PO) twice daily (BID) on days 1-28 and nivolumab intravenously (IV) over 30 minutes, or per institutional guidelines, on days 1 and 15 (if < 18 years old) or on day 1 (if >= 18 years old). Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive axitinib PO BID on days 1-28. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. (CLOSED TO ACCRUAL AS OF 1/23/2020 - PROSPECTIVE PATIENTS ARE RANDOMLY ASSIGNED TO ARMS A OR C)
ARM C: Patients receive nivolumab IV over 30 minutes, or per institutional guidelines, on days 1 and 15 (if < 18 years old) or on day 1 (if >= 18 years old). Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, and every 6 months for 2 years. Follow-up at year 5 and beyond is at the discretion of the treating physician.
- Patients must be >= 12 months at enrollment
- Patients must have a body surface area (BSA) >= 0.53 m^2
- Histologically confirmed unresectable or metastatic translocation morphology renal cell carcinoma diagnosed using World Health Organization (WHO)-defined criteria. Patients may be newly diagnosed or have received prior cancer therapy
* Patients must have had histologic verification of the malignancy
* Patients must have measurable disease, documented by clinical, radiographic, or histologic criteria as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
* Patients must have a tumor showing the appropriate morphologic appearance, and either confirmed TFE3 nuclear protein expression by immunohistochemistry with appropriate positive and negative controls performed at a Clinical Laboratory Improvement Act (CLIA)-certified laboratory, or evidence of TFE3 or TFEb translocation by either fluorescence in situ hybridization (FISH) or reverse transcriptase- polymerase chain reaction (RT-PCR) performed at a CLIA-certified laboratory. For TFE3 immunohistochemistry, any nuclear positivity in the presence of appropriate positive and negative controls should be considered as evidence of TFE3 immunohistochemical expression. NOTE: If the institution is unable to perform these studies, unstained slides may be submitted to Dr. Elizabeth Perlman, who will perform TFE3 analysis at no charge. The slide will be returned to the referring institution for local evaluation, to be included in their institutional report
- Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
- Patients must have a life expectancy of >= 8 weeks
- Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
* Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry onto this study (6 weeks if prior nitrosourea)
* Immunotherapy: Must not have received within 4 weeks of entry onto this study
* Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent
* Radiation therapy (RT): >= 2 weeks for local palliative RT (small port); >= 6 months must have elapsed if prior craniospinal RT or if >= 50% radiation of pelvis; >= 6 weeks must have elapsed if other substantial bone marrow (BM) radiation
- Peripheral absolute neutrophil count (ANC) >= 1000/uL (performed within 7 days prior to enrollment)
- Platelet count >= 75,000/uL (transfusion independent) (performed within 7 days prior to enrollment)
- Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (performed within 7 days prior to enrollment)
- Urine protein: =< 30 mg/dL in urinalysis or =< 1+ on dipstick, unless quantitative protein is < 1000 mg in a 24 hours (h) urine sample (performed within 7 days prior to enrollment)
- For patients < 18 years of age: Serum creatinine =< 1.5 x upper limit of normal (ULN), or measured or calculated creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 60 mL/min/1.73 m^2 for patient with creatinine levels > 1.5 x institutional ULN, or a serum creatinine based on age/gender as follows (performed within 7 days prior to enrollment):
* 1 to < 2 years - 0.6 mg/dL (male, female)
* 2 to < 6 years - 0.8 mg/dL (male, female)
* 6 to < 10 years - 1 mg/dL (male, female)
* 10 to < 13 years - 1.2 mg/dL (male, female)
* 13 to < 16 years - 1.5 mg/dL (male), 1.4 mg/dL (female)
* >= 16 years - 1.7 mg/dL (male), 1.4 mg/dL (female)
* Creatinine clearance should be calculated per institutional standard
- For patients >= 18 years of age: Serum creatinine =< 2 x ULN, or measured or calculated creatinine clearance or radioisotope GFR >= 40 mL/min/1.73 m^2 for patient with creatinine levels > 2 x institutional ULN (performed within 7 days prior to enrollment)
* Creatinine clearance should be calculated per institutional standard
- Serum total bilirubin =< 1.5 x ULN for age, or direct bilirubin =< ULN for patients with total bilirubin levels > 1.5 X ULN (performed within 7 days prior to enrollment)
- Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 3 x ULN for age (performed within 7 days prior to enrollment)
- Albumin > 2.5 mg/dL (performed within 7 days prior to enrollment)
- Shortening fraction of >= 27% by echocardiogram, or
- Ejection fraction of >= 50% by radionuclide angiogram
- No history of myocardial infarction, severe or unstable angina, or peripheral vascular disease
- Corrected QT (QTc) =< 480 msec. Note: Patients with grade 1 prolonged QTc (450-480 msec) at the time of study enrollment should have correctable causes of prolonged QTc addressed if possible (i.e., electrolytes, medications)
- International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN. However, if patient is receiving anticoagulant therapy, PT or partial thromboplastin time (PTT) should be within therapeutic range of intended use of anticoagulants
- Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- A baseline blood pressure (BP) =< the 95th percentile for age, height, and gender for patients < 18 years old, or =< 150 mmHg (systolic) and =< 90 mmHg (diastolic) for patients >= 18 years old
* Note: 2 serial blood pressures should be taken at least 1 hour apart and averaged to determine baseline BP
- Patients are eligible if on stable doses (>= 7 days) of anti-hypertensive medications with a baseline BP meeting the criteria above
Treatment Sites in Georgia
1405 Clifton Road NE
Atlanta, GA 30322
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