High Dose IL-2 and Stereotactic Ablative Body Radiation Therapy for Metastatic Renal Cancer
Condition: Metastatic Clear Cell Renal Cell Carcinoma
MeSH terms: Carcinoma, Renal Cell
Intervention: IL-2; Stereotactic Ablative Body Radiation Therapy
Intervention description: HD IL-2 (brand name Proleukin), 600,000 U/kg q8h X 14 dose, IV infusion; SABR dose varying from 8Gy-20Gy in 1-3 fractions
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: kidney cancer; metastatic cancer

Summary:

      In this i-SABR (immunotherapy + Stereotactic Ablative Body Radiation) trial, the stereotactic
      radiation to multiple metastatic sites is delivered not only to eradicate sites of bulky
      progressive disease, but also to provide antigen presentation and immune stimulation which is
      expected to act synergistically when immediately followed by the non-specific immune
      stimulation provided by treatment with HD IL-2 and thereby increase the response rate and
      complete response for metastatic clear cell renal cell cancer patients. Both HD IL-2 and SABR
      are FDA approved therapeutic cancer treatment
    

Eligibility criteria:

        Inclusion Criteria:

          1. Biopsy-proven metastatic clear cell RCC.

          2. Radiographic evidence of metastatic disease. 2.1 Patients with any number of
             metastatic site are allowed to enroll. However, only up to six sites will be selected
             for SBRT treatment, at the discretion of the treating radiation oncologist.

          3. Patient must have ≥1 lesion of size >1.5cm.

          4. Previous treatment with surgery, radiation, chemotherapy, immunotherapy or any
             targeted agents are allowed 28 days before the start of HD IL-2

          5. Age ≥ 18 years.

          6. Performance status ECOG 0, 1.

          7. Patient must be eligible for HD IL-2 treatment

          8. Patient must be eligible for SABR to one or more extra cranial sites.

          9. Adequate organ and marrow function as defined below:

               -  leukocytes ≥ 3,000/mcL

               -  absolute neutrophil count ≥ 1,500/mcL

               -  platelets ≥ 50,000/mcl

               -  total bilirubin ≤ 2mg/dL

               -  AST(SGOT)/ALT(SPGT) ≤ 2.5 X institutional upper limit of normal

         10. Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry, for
             the duration of study participation. Should a woman become pregnant or suspect she is
             pregnant while participating in this study, she should inform her treating physician
             immediately.

             10.1 A female of child-bearing potential is any woman (regardless of sexual
             orientation, having undergone a tubal ligation, or remaining celibate by choice) who
             meets the following criteria:

               -  Has not undergone a hysterectomy or bilateral oophorectomy; or

               -  Has not been naturally postmenopausal for at least 12 consecutive months (i.e.,
                  has had menses at any time in the preceding 12 consecutive months).

         11. Ability to understand and the willingness to sign a written informed consent

         12. Adequate Renal function with Cr ≤ 1.6 mg/dL.

         13. Adequate cardiac function (adequate perfusion; no ischemia) on thallium (or Tc) stress
             test

         14. Adequate pulmonary function on PFT (FEV1 >65%; DLCO>60%).

        Exclusion Criteria:

          1. Subjects who have had chemotherapy or radiotherapy within 4 weeks prior to entering
             the study

          2. History of HIV, Hepatitis B, Hepatitis C and HTLV serology

          3. Subjects may not be receiving any other investigational or standard antineoplastic
             agents.

          4. Subjects with known brain metastases should be excluded from this clinical trial
             because of their poor prognosis

          5. Subjects with life expectancy < 6 months.

          6. History of allergic reactions to recombinant IL-2

          7. Uncontrolled recurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia,.

          8. Psychiatric illness/social situations that would limit compliance with study
             requirements.

          9. Subjects must not be pregnant or nursing due to the potential for congenital
             abnormalities and the potential of this regimen to harm nursing infants.

         10. Systemic or topical steroid use or other immunosuppressive therapy within the past 28
             days

         11. Subjects required to take corticosteroids or other immunosuppressive therapy such as
             those with organ allograft