High Dose IL-2 and Stereotactic Ablative Body Radiation Therapy for Metastatic Renal Cancer

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)

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

Study Overview

• Status: Completed
• Conditions: Metastatic Clear Cell Renal Cell Carcinoma
• Intervention / Treatment: Drug: IL-2; Radiation: Stereotactic Ablative Body Radiation Therapy

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: treatment; 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.	Drug: IL-2; HD IL-2 (brand name Proleukin), 600,000 U/kg q8h X 14 dose, IV infusion; Radiation: Stereotactic Ablative Body Radiation Therapy; SABR dose varying from 8Gy-20Gy in 1-3 fractions; Other Names: SABR, SBRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate	Treatment response will be measured using the immune related Response Evaluation Criteria in Solid Tumors (RECIST) criteria (iRECIST) which are a minor modification of RECIST 1.1 for immunotherapy	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall Survival (OS), which is defined as the time between date of registration and the date of death due to any cause.	4 years
Progression Free Survival	Progression Free Survival (PFS), which is defined according to the immune Response Evaluation Criteria in Solid Tumors (iRECIST) as the time between date of registration and the first date of documented disease progression or date of death due to any cause.	4 years
Time to Progression	Time to Progression (TTP), which is defined as time between date of registration and date of documented progression	4 years
Local Control Rate	Local recurrence is defined as tumor recurrence within the planning target volume. Local control rate will be evaluated by imaging techniques such as CT or MRI. Local recurrence will be defined as an increase of > 20% in tumor size.	4 years
Median Response Duration	Median response duration, which is defined as the time between the date a response (CR or PR) was first seen until date of progression	4 years
Tumor-specific Immune Response	Immune response will be measured using ELISpot assay, T-cell proliferation assay and ELISA.	4 years
Number of Participants With Adverse Events	Adverse events will be determined according to Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.	4 years
Health-related Quality of Life (HRQoL).		4 years

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: Prometheus Laboratories
• Investigators: Principal Investigator: Raquibul Hannan, MD, PhD, University of Texas Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2013
• Primary Completion (Actual): August 25, 2020
• Study Completion (Actual): April 20, 2021

Study Registration Dates

• First Submitted: July 5, 2013
• First Submitted That Met QC Criteria: July 5, 2013
• First Posted (Estimate): July 11, 2013

Study Record Updates

• Last Update Posted (Actual): August 23, 2021
• Last Update Submitted That Met QC Criteria: July 28, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: kidney cancer; metastatic cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell
• Other Study ID Numbers: STU 012013-041

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No