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

• ClinicalTrials.gov Identifier: NCT01896271
• Recruitment Status: Active, not recruiting
• First Posted: July 11, 2013
• Last Update Posted: August 20, 2020
• Sponsor: University of Texas Southwestern Medical Center
• Collaborator: Prometheus Laboratories
• Information provided by (Responsible Party): University of Texas Southwestern Medical Center

Study Description

Brief 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

Condition or disease	Intervention/treatment	Phase
Metastatic Clear Cell Renal Cell Carcinoma	Drug: IL-2; Radiation: Stereotactic Ablative Body Radiation Therapy	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 26 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: October 2, 2013
• Estimated Primary Completion Date: December 20, 2022
• Estimated Study Completion Date: December 2023

Arms and Interventions

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 Name: SABR, SBRT

Outcome Measures

Primary Outcome Measures :

1. Response rate [ Time Frame: 6 months ]
   To evaluate the response rate (RR) in patients with mRCC after treatment with HD IL-2 immediately following SABR to multiple metastatic sites. RR has been highly correlated (p<0.0001) to overall survival. RECIST 1.1 criteria will be used to measure RR and it will consist of complete response (CR) and partial response (PR)

Secondary Outcome Measures :

1. Overall survival [ Time Frame: 4 years ]
   To evaluate the overall survival (OS), which is defined as the time between date of registration and the date of death due to any cause. In analyzing the OS, it is important to take into account the MSKCC prognostic criteria defined by Motzer et. al. mRCC patients and compare the outcome in the appropriate risk categories
2. Progression free survival [ Time Frame: 4 years ]
   To evaluate progression free survival (PFS), which is defined as the time between date of registration and the first date of documented disease progression or date of death due to any cause.
3. Time to progression [ Time Frame: 4 years ]
   To evaluate time to progression (TTP), which is defined as time between date of registration and date of documented progression
4. Median response duration [ Time Frame: 4 years ]
   To evaluate median response duration, which is defined as the time between the date a response (CR or PR) was first seen until date of progression
5. Local control rate [ Time Frame: 4 years ]
   To evaluate the local control rate of irradiated lesions
6. Tumor-specific immune response [ Time Frame: 4 years ]
   To measure treatment-related tumor-specific immune response
7. Toxicity [ Time Frame: 4 years ]
   To evaluate the tolerability and toxicity of this regiment as measured according to CTCAE v4.0.
8. Health-related quality of life (HRQoL). [ Time Frame: 4 years ]
   To measure the improvement in health-related quality of life (HRQoL)

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, Texas

University of Texas Southwestern Medical Center

Dallas, Texas, United States, 75390

Sponsors and Collaborators

University of Texas Southwestern Medical Center

Prometheus Laboratories

Investigators

• Principal Investigator: Raquibul Hannan, MD, PhD; University of Texas Southwestern Medical Center

More Information

• Responsible Party: University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT01896271
• Other Study ID Numbers: STU 012013-041
• First Posted: July 11, 2013
• Last Update Posted: August 20, 2020
• Last Verified: March 2020

Keywords provided by University of Texas Southwestern Medical Center:

kidney cancer; metastatic cancer

Additional relevant MeSH terms:

Carcinoma, Renal Cell; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases