Metastatic Clear Cell Renal Cell Carcinoma
Conditions
Keywords
kidney cancer, metastatic cancer
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
Interventions
DRUGIL-2
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
Sponsors
Prometheus Laboratories
University of Texas Southwestern Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Time to Progression | 4 years | Time to Progression (TTP), which is defined as time between date of registration and date of documented progression |
| 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. |
| 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. |
| Tumor-specific Immune Response | 4 years | Immune response will be measured using ELISpot assay, T-cell proliferation assay and ELISA. |
| 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. |
| Health-related Quality of Life (HRQoL). | 4 years | — |
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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 | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 10 |
Baseline characteristics
| Characteristic | Treatment |
|---|---|
| Age, Continuous | 51.5 years |
| Race/Ethnicity, Customized Non-white | 5 Participants |
| Race/Ethnicity, Customized White | 25 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 19 / 30 |
| other Total, other adverse events | 30 / 30 |
| serious Total, serious adverse events | 22 / 30 |
Outcome results
Primary
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
Time frame: 6 months
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Response Rate | 4 Participants |
Secondary
Health-related Quality of Life (HRQoL).
Time frame: 4 years
Population: The data were never collected from the participants.
Secondary
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.
Time frame: 4 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Local Control Rate | 30 lesions |
Secondary
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
Time frame: 4 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment | Median Response Duration | 26.7 months |
Secondary
Number of Participants With Adverse Events
Adverse events will be determined according to Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
Time frame: 4 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Number of Participants With Adverse Events | 30 Participants |
Secondary
Overall Survival
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment | Overall Survival | 39 months |
Secondary
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.
Time frame: 4 years
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment | Progression Free Survival | 2.5 months |
Secondary
Time to Progression
Time to Progression (TTP), which is defined as time between date of registration and date of documented progression
Time frame: 4 years
Population: 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.
Secondary
Tumor-specific Immune Response
Immune response will be measured using ELISpot assay, T-cell proliferation assay and ELISA.
Time frame: 4 years
Population: This data were never collected from the participants.