A Phase II Trial of High Dose IL-2 and Stereotactic Ablative Body Radiation Therapy (SABR) for Patients with Metastatic Clear Cell Renal Cell Cancer (mRCC)

Summary

a single-arm, open-label, phase ii trial of HD iL-2 and SaBR to multiple sites of bulky disease. The toxicities of HD iL-2 are significant and well known. Given the multiple studies demonstrating excellent safety profile of SaBR, including our own departmental experience, there are limited concerns for additional toxicity when they are administered sequentially.

endpoints
1 Response: Treatment response will be measured using the immune related ReCiST criteria (iReCiST) which are a minor modification of ReCiST 1.1 for immunotherapy [91].
2 Death: Death due to any cause, although in mRCC patient population, the overwhelming majority is expected to be secondary to disease progression.
3 Progression: Progression will be defined according to the iReCiST criteria and verified by a second set of imaging at least 6 weeks apart.
4 immune Response: immune response will be measured using eLiSpot assay, T-cell proliferation assay and eLiSa.
5 Toxicity: Toxicity will be measured using CTae v4.0
6 HRQoL: HRQoL will be measured using FaCT-G, eQ-5D and FKSi questionnaire at baseline, during treatment on day 1 and 28 of each cycle, and at two-month intervals after treatment.
7 Cost-effectiveness analysis: Health care utilization data needed to assess costs will be obtained from treatment records to include costs of hospitalization, treatment, eR visits, physician and clinic visits and medications. Markov modeling with probabilistic sensitivity analysis will be used to correlate quality-adjusted survival and cost.

Participant Eligibility

3.1.1 Biopsy-proven metastatic clear cell RCC.

3.1.1.1 If previous biopsy of metastatic site within six months exists and a review of slides shows it to be adequate, then a pretreatment biopsy is optional..


3.1.2 Radiographic evidence of metastatic disease. CT and Bone Scan must be performed with 21 days (+ 7 days) of registration. MRI can be performed within 3 months prior to registration.

3.1.3.1 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.

3.1.3 Patient must have >1 lesion. Combined diameter of the lesions must be of size >1.5cm.

3.1.4 Previous treatment with surgery, radiation, chemotherapy, immunotherapy or any targeted agents are allowed provided that:

3.1.4.1 Chemotherapy was administered > 28 days before the start of HD IL-2

3.1.4.2 Surgery, radiation, immunotherapy or any targeted agents was administered > 14 days before the start of HD IL-2


3.1.5 Age >= 18 years.

3.1.6 Performance status ECOG 0, 1.

3.1.7 Patient must be eligible for HD IL-2 treatment

3.1.8 Patient must be eligible for SABR to one or more extra cranial sites
3.1.9 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

3.1.10 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.

3.1.6.1 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).

3.1.11 Ability to understand and the willingness to sign a written informed consent

3.1.12 Adequate Renal function with Cr <= 1.6 mg/dL.

3.1.13 Adequate cardiac function (adequate perfusion; no ischemia) on thallium (or Tc) stress test

3.1.14 Adequate pulmonary function on PFT (FEV1 >65%; DLCO>60%).