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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University of Texas Southwestern Medical Center
Sponsor:
Collaborator:
Prometheus Therapeutics and Diagnostics
Information provided by (Responsible Party):
University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:
NCT01896271
First received: July 5, 2013
Last updated: May 19, 2014
Last verified: May 2014
  Purpose

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 Intervention Phase
Metastatic Clear Cell Renal Cell Carcinoma
Drug: IL-2
Radiation: Stereotactic Ablative Body Radiation Therapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by University of Texas Southwestern Medical Center:

Primary Outcome Measures:
  • Response rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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:
  • Overall survival [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    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

  • Progression free survival [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    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.

  • Time to progression [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    To evaluate time to progression (TTP), which is defined as time between date of registration and date of documented progression

  • Median response duration [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    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

  • Local control rate [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    To evaluate the local control rate of irradiated lesions

  • Tumor-specific immune response [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    To measure treatment-related tumor-specific immune response

  • Toxicity [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
    To evaluate the tolerability and toxicity of this regiment as measured according to CTCAE v4.0.

  • Health-related quality of life (HRQoL). [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    To measure the improvement in health-related quality of life (HRQoL)


Estimated Enrollment: 26
Study Start Date: September 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01896271

Contacts
Contact: Raquibul Hannan, MD, PhD 214-645-8525 raquibul.hannan@utsouthwestern.edu

Locations
United States, Texas
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Principal Investigator: Raquibul Hannan, MD, PhD         
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Prometheus Therapeutics and Diagnostics
Investigators
Principal Investigator: Raquibul Hannan, MD, PhD University of Texas Southwestern Medical Center
  More Information

No publications provided

Responsible Party: University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT01896271     History of Changes
Other Study ID Numbers: STU 012013-041
Study First Received: July 5, 2013
Last Updated: May 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Texas Southwestern Medical Center:
kidney cancer
metastatic cancer

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Interleukin-2
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 28, 2014