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

• Sponsor: University of Texas Southwestern Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01896271
• Collaborator: Prometheus Laboratories (Industry)
• Enrollment: 30
• Location: 1
• Arm: 1
• Actual Duration (Months): 90.6
• Patients Per Site Per Month: 0.3

Study Details

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
• Actual Enrollment: 30 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: Oct 2, 2013
• Actual Primary Completion Date: Aug 25, 2020
• Actual Study Completion Date: Apr 20, 2021

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 Names: SABR, SBRT

Outcome Measures

Primary Outcome Measures

1. Response Rate [6 months]

   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

Secondary Outcome Measures

1. Overall Survival [4 years]

   Overall Survival (OS), which is defined as the time between date of registration and the date of death due to any cause.

2. Progression Free Survival [4 years]

   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.

3. Time to Progression [4 years]

   Time to Progression (TTP), which is defined as time between date of registration and date of documented progression

4. Local Control Rate [4 years]

   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.

5. Median Response Duration [4 years]

   Median response duration, which is defined as the time between the date a response (CR or PR) was first seen until date of progression

6. Tumor-specific Immune Response [4 years]

   Immune response will be measured using ELISpot assay, T-cell proliferation assay and ELISA.

7. Number of Participants With Adverse Events [4 years]

   Adverse events will be determined according to Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.

8. Health-related Quality of Life (HRQoL). [4 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

1. 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).

1. Ability to understand and the willingness to sign a written informed consent

2. Adequate Renal function with Cr ≤ 1.6 mg/dL.

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

4. 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

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 20, 2019
• Informed Consent Form - May 20, 2019

More Information

Publications

None provided.

• Responsible Party: Raquibul Hannan, Principal Investigator, University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT01896271
• Other Study ID Numbers: STU 012013-041
• First Posted: Jul 11, 2013
• Last Update Posted: Aug 23, 2021
• Last Verified: Jul 1, 2021

• Keywords provided by Raquibul Hannan, Principal Investigator, University of Texas Southwestern Medical Center: kidney cancer; metastatic cancer
• Additional relevant MeSH terms: Carcinoma, Renal Cell

Study Results

Participant Flow

Arm/Group Title	Treatment
Arm/Group 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. IL-2: HD IL-2 (brand name Proleukin), 600,000 U/kg q8h X 14 dose, IV infusion Stereotactic Ablative Body Radiation Therapy: SABR dose varying from 8Gy-20Gy in 1-3 fractions
Period Title: Overall Study
STARTED	30
COMPLETED	20
NOT COMPLETED	10

Baseline Characteristics

Arm/Group Title	Treatment
Arm/Group 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. IL-2: HD IL-2 (brand name Proleukin), 600,000 U/kg q8h X 14 dose, IV infusion Stereotactic Ablative Body Radiation Therapy: SABR dose varying from 8Gy-20Gy in 1-3 fractions
Overall Participants	30
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	51.5
Sex: Female, Male (Count of Participants)
Female	11 36.7%
Male	19 63.3%
Race/Ethnicity, Customized (Count of Participants)
White	25 83.3%
Non-white	5 16.7%

Outcome Measures

1. Primary Outcome

Title	Response Rate
Description	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
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

There were 5 patients without measurable disease at baseline and 5 additional patients without 2nd scan to confirm progression. Hence, they were not analyzed.

Arm/Group Title	Treatment
Arm/Group 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. IL-2: HD IL-2 (brand name Proleukin), 600,000 U/kg q8h X 14 dose, IV infusion Stereotactic Ablative Body Radiation Therapy: SABR dose varying from 8Gy-20Gy in 1-3 fractions
Measure Participants	20
Count of Participants [Participants]	4 13.3%

2. Secondary Outcome

Title	Overall Survival
Description	Overall Survival (OS), which is defined as the time between date of registration and the date of death due to any cause.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment
Arm/Group 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. IL-2: HD IL-2 (brand name Proleukin), 600,000 U/kg q8h X 14 dose, IV infusion Stereotactic Ablative Body Radiation Therapy: SABR dose varying from 8Gy-20Gy in 1-3 fractions
Measure Participants	30
Median (95% Confidence Interval) [months]	39

3. Secondary Outcome

Title	Progression Free Survival
Description	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.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

There were 5 patients without measurable disease at baseline and 5 additional patients without 2nd scan to confirm progression. Hence, they were not analyzed.

Arm/Group Title	Treatment
Arm/Group 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. IL-2: HD IL-2 (brand name Proleukin), 600,000 U/kg q8h X 14 dose, IV infusion Stereotactic Ablative Body Radiation Therapy: SABR dose varying from 8Gy-20Gy in 1-3 fractions
Measure Participants	20
Median (95% Confidence Interval) [months]	2.5

4. Secondary Outcome

Title	Time to Progression
Description	Time to Progression (TTP), which is defined as time between date of registration and date of documented progression
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

This outcome measure was inadvertently added at the time of registration. This is same as progression free survival and measures and reports the exact same thing and is redundant. No separate data was collected from participants for this specific measure.

Arm/Group Title	Treatment
Arm/Group 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. IL-2: HD IL-2 (brand name Proleukin), 600,000 U/kg q8h X 14 dose, IV infusion Stereotactic Ablative Body Radiation Therapy: SABR dose varying from 8Gy-20Gy in 1-3 fractions
Measure Participants	0

5. Secondary Outcome

Title	Local Control Rate
Description	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.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment
Arm/Group 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. IL-2: HD IL-2 (brand name Proleukin), 600,000 U/kg q8h X 14 dose, IV infusion Stereotactic Ablative Body Radiation Therapy: SABR dose varying from 8Gy-20Gy in 1-3 fractions
Measure Participants	30
Measure lesions	31
Number [lesions]	30

6. Secondary Outcome

Title	Median Response Duration
Description	Median response duration, which is defined as the time between the date a response (CR or PR) was first seen until date of progression
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment
Arm/Group 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. IL-2: HD IL-2 (brand name Proleukin), 600,000 U/kg q8h X 14 dose, IV infusion Stereotactic Ablative Body Radiation Therapy: SABR dose varying from 8Gy-20Gy in 1-3 fractions
Measure Participants	20
Median (Inter-Quartile Range) [months]	26.7

7. Secondary Outcome

Title	Tumor-specific Immune Response
Description	Immune response will be measured using ELISpot assay, T-cell proliferation assay and ELISA.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

This data were never collected from the participants.

Arm/Group Title	Treatment
Arm/Group 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. IL-2: HD IL-2 (brand name Proleukin), 600,000 U/kg q8h X 14 dose, IV infusion Stereotactic Ablative Body Radiation Therapy: SABR dose varying from 8Gy-20Gy in 1-3 fractions
Measure Participants	0

8. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	Adverse events will be determined according to Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment
Arm/Group 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. IL-2: HD IL-2 (brand name Proleukin), 600,000 U/kg q8h X 14 dose, IV infusion Stereotactic Ablative Body Radiation Therapy: SABR dose varying from 8Gy-20Gy in 1-3 fractions
Measure Participants	30
Count of Participants [Participants]	30 100%

9. Secondary Outcome

Title	Health-related Quality of Life (HRQoL).
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

The data were never collected from the participants.

Arm/Group Title	Treatment
Arm/Group 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. IL-2: HD IL-2 (brand name Proleukin), 600,000 U/kg q8h X 14 dose, IV infusion Stereotactic Ablative Body Radiation Therapy: SABR dose varying from 8Gy-20Gy in 1-3 fractions
Measure Participants	0

Adverse Events

Time Frame	4 years
Arm/Group Title	Treatment
Arm/Group 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. IL-2: HD IL-2 (brand name Proleukin), 600,000 U/kg q8h X 14 dose, IV infusion Stereotactic Ablative Body Radiation Therapy: SABR dose varying from 8Gy-20Gy in 1-3 fractions
All Cause Mortality
	Treatment
	Affected / at Risk (%)	# Events
Total	19/30 (63.3%)
Serious Adverse Events
	Treatment
	Affected / at Risk (%)	# Events
Total	22/30 (73.3%)
Blood and lymphatic system disorders
Hematology Coagulation	8/30 (26.7%)
Cardiac disorders
Cardiac	3/30 (10%)
Hypotension	2/30 (6.7%)
Gastrointestinal disorders
Gastrointestinal	1/30 (3.3%)
General disorders
Other	1/30 (3.3%)
Hepatobiliary disorders
Hepatobiliary disorders	3/30 (10%)
Infections and infestations
Infection	3/30 (10%)
Nervous system disorders
Neurologic	1/30 (3.3%)
Renal and urinary disorders
Renal/electrolytes	11/30 (36.7%)
Respiratory, thoracic and mediastinal disorders
Respiratory	3/30 (10%)
Other (Not Including Serious) Adverse Events
	Treatment
	Affected / at Risk (%)	# Events
Total	30/30 (100%)
Blood and lymphatic system disorders
Hematology Coagulation	28/30 (93.3%)
Cardiac disorders
Cardiac	22/30 (73.3%)
Hypotension	18/30 (60%)
Gastrointestinal disorders
Gastrointestinal	22/30 (73.3%)
General disorders
Constitutional	27/30 (90%)
Other	14/30 (46.7%)
Hepatobiliary disorders
Hepatobiliary disorders	19/30 (63.3%)
Infections and infestations
Infection	5/30 (16.7%)
Nervous system disorders
Neurologic	12/30 (40%)
Psychiatric disorders
Psychiatric	6/30 (20%)
Renal and urinary disorders
Renal/electrolytes	29/30 (96.7%)
Respiratory, thoracic and mediastinal disorders
Respiratory	13/30 (43.3%)
Skin and subcutaneous tissue disorders
Skin	21/30 (70%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.