Renal Cell CarcinomaPhase 2NCT04974671
Trial Of Stereotactic Body Radiation Therapy (SBRT) for Oligoprogression on Immune Checkpoint Inhibitors (ICI) in Metastatic Renal Cell Carcinoma
A Phase 2 study testing Stereotactic Body Radiation Therapy in people with Renal Cell Carcinoma and Metastatic Renal Cell Carcinoma, run by Yale University at 1 site in United States.
Trial summary
This Phase II trial will evaluate progression-free survival after Stereotactic Body Radiation Therapy to oligoprogressive (1-5) lesions in metastatic renal cell carcinoma patients on any immune checkpoint inhibitor-containing regimen with last dose of systemic therapy within 3 months prior to trial enrollment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Cell Carcinoma, Metastatic Renal Cell Carcinoma, Oligoprogressive
- What is being tested?
- Stereotactic Body Radiation Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Dec 2023to 1 Apr 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- In order to be eligible for participation in this trial, the subject must:
- Be willing and able to provide written informed consent/assent for the trial
- Be ≥ 18 years of age on day of signing informed consent.
- Have histologically confirmed renal cell carcinoma with metastatic disease detected on imaging. Biopsy of metastasis is preferred but not required
- The subject has a performance status of 0, 1, or 2 on the ECOG Performance Scale
- The life expectancy is > 6 months
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- The most recent systemic therapy must be an ICI-containing regimen, delivered for at least 3 months prior to development of oligoprogressive lesions, with the last dose received within 3 months of trial enrollment.
- Oligoprogression - defined as documented progression in up to 5 individual lesions with no previous local therapy to those sites using one of the following criteria:
- 7.1 RECIST 1.1 7.1.1 At least a 20% increase in the sum of diameters of target lesions (long axis for non-nodal lesions, short axis for nodal lesions), using the previous imaging as a baseline 7.1.2 The sum of all diameters must demonstrate an absolute increase of at least 5 mm 7.1.3 The appearance of at least one new unequivocal lesion 7.2 PERCIST 7.2.1 SUVpeak, normalized to lean body mass (SUL) increase by at least 30% and increase by at least 0.8 SUL of the target lesion 7.2.2 Development of at least one new lesion 7.2.3 Increase in target lesion size by 30% 7.2.4 Unequivocal progression of nontarget lesions 7.3 Progressive enlargement of a known metastasis on 2 consecutive imaging studies at least 2 months apart with a minimum 5 mm increase in size 7.4 Development of a new soft tissue metastatic lesion at least 5 mm in size or any new bone metastasis
- There is no restriction on the total number of metastases
- Demonstrate adequate organ function as defined in Table 4, all screening labs should be performed within 28 days of protocol treatment
- Table 4 Adequate Organ Function Laboratory Values
- System Laboratory Value
- Hematological
- Absolute neutrophil count (ANC) ≥ 1,500 /mcL Platelets ≥ 75,000 / mcL Hemoglobin ≥ 9 g/dL
- Renal - IF SBRT will be delivered to a lesion in or abutting the kidney
- Serum creatinine OR ≤1.5 X upper limit of normal (ULN) OR Measured or calculated creatinine clearance (GFR can also be used in ≥30 mL/min for subject with creatinine place of creatinine or CrCl) levels > 1.5 X institutional ULN
- Hepatic - IF SBRT will be delivered to a lesion in or abutting the liver
- Serum total bilirubin ≤ 1.5 X ULN Direct bilirubin Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR
- 5 X ULN for subjects with liver metastases
- Creatinine clearance should be calculated per institutional standard
- Able to be treated with SBRT at a Yale radiation oncology facility
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of SBRT. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Female subjects of childbearing must use an effective form of birth control during this study. Acceptable and highly effective birth control methods include intra-uterine hormone releasing system as well as other methods of birth control including consistent use of an approved oral contraceptive (birth control pill), an implantable contraceptive, an injectable contraceptive, a double-barrier method, or true abstinence. Oral, implantable, or injectable contraceptives are only considered effective if used properly and started at least 30 days prior to the screening visit and continue for 120 days after last dose of study drug. (Reference Section 5.7)
- Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study therapy
Who cannot join
- The subject must be excluded from participating in the trial if the subject
- Has had radiation therapy within 2 weeks of the first protocol treatment.
- Has brain-only oligoprogression. subjects with brain and systemic oligoprogression can still be considered, however treatment of brain metastases will be per standard of care prior to receiving study SBRT.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 2 weeks of the first protocol treatment. The use of lowdose steroids for management of chronic conditions is allowed (up to 12mg prednisone orally per day or the equivalent).
- Has had prior radiation therapy within 2 weeks of the first protocol treatment.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
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- Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an example of an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Those with a history of hypothyroidism who are now stable on hormone replacement will not be excluded. Those with Sjorgen's syndrome will not be excluded from the study.
- Has a history of (non-infectious) pneumonitis that required steroids, current pneumonitis, or underlying lung disease that according to the treating physician makes the patient ineligible.
- Has an active infection requiring systemic therapy.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Has received a live vaccine within 30 days prior to the first protocol treatment.
- Has serious medical comorbidities precluding radiotherapy. These include subjects with connective tissue diseases such as lupus or scleroderma, Crohn's disease in subjects where the GI tract will receive radiation
- Substantial overlap with a previously treated radiation volume. Prior radiotherapy is allowed as long as the composite plan meets dose constraints
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Yale University
New Haven, Connecticut, 06520
About this study
Official title: Phase II Trial Of Stereotactic Body Radiation Therapy (SBRT) for Oligoprogression on Immune Checkpoint Inhibitors (ICI) in Metastatic Renal Cell Carcinoma
This Phase II trial will evaluate progression-free survival after Stereotactic Body Radiation Therapy to oligoprogressive (1-5) lesions in metastatic renal cell carcinoma patients on any immune checkpoint inhibitor-containing regimen with last dose of systemic therapy within 3 months prior to trial enrollment.
Read the detailed description
This Phase II trial will evaluate progression-free survival after Stereotactic Body Radiation Therapy to oligoprogressive (1-5) lesions in metastatic renal cell carcinoma patients on any immune checkpoint inhibitor-containing regimen with last dose of systemic therapy within 3 months prior to trial enrollment. Alternative local therapy (including but not limited to metastectomy or radiofrequency ablation) to one or more of the oligoprogressive lesions is allowed provided at least one of the lesions is receiving Stereotactic Body Radiation Therapy. Stereotactic Body Radiation Therapy will be delivered on nonconsecutive days (if >1 fraction) for a total of 1-5 fractions depending on anatomic site at the treating physicians discretion. Treatment to multiple sites can be delivered sequentially or concurrently, at the treating physicians discretion. Patients will undergo response-assessment imaging (CT chest/abdomen/pelvis with IV contrast and/or PET CT scan and/or MRI plus or minus contrast), and response to treatment will be measured via RECIST. The acute and long-term toxicity will be monitored and graded per CTCAE 5.0 (https://ctep.cancer.gov/). Patients will continue on the same immune checkpoint inhibitor-containing regimen during Stereotactic Body Radiation Therapy planning and delivery, and after completion of Stereotactic Body Radiation Therapy until progression of disease as defined by RECIST criteria. The immune checkpoint inhibitor-containing regimen can be continued beyond RECIST progression of disease if the treating physician feels that a patient will continue to benefit. Each eligible patient will be discussed at a multidisciplinary tumor board in the presence of medical and radiation oncology and will be seen in consultation in a Yale-affiliated radiation oncology department prior to enrollment in the trial.
- Being tested
- Stereotactic Body Radiation Therapy
- Medical subject headings
- Carcinoma, Renal Cell, Disease Progression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stereotactic Body Radiation TherapyRadiation
1-5 fraction Stereotactic Body Radiation Therapy to all sites of progression
| Study group | Role | What they receive |
|---|---|---|
| Stereotactic Body Radiation Therapy | Experimental | Not described Receives: Radiation: Stereotactic Body Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival
The primary objective of this study is to assess progression free survival after SBRT to all sites of progression and continuation of the same systemic regimen in patients with mRCC on ICI-containing systemic regimens with oligoprogression at 1-5 sites. Progression will be defined by RECIST criteria.
Measured: 6 Months
Secondary outcomes (3)
Recurrence
Imaging will be done every three months to determine rate of recurrence.
Measured: Up to two years
Rate of Response
To determine rate of response at non-treated sites. Imaging will be done every three months.
Measured: Up to two years
Overall survival
Overall survival will be assessed up to two years
Measured: Up to two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2021
- Study start22 Dec 2023
- Primary completion1 Jan 2027 (estimated)
- Study completion1 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kimberly Johung, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04974671
- Sponsor's protocol ID
- 2000027702
- Other IDs
- No NIH funding
- Status last verified
- Dec 2025
- First submitted
- 13 Jul 2021
- Last updated
- 4 Dec 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial Of Stereotactic Body Radiation Therapy (SBRT) for Oligoprogression on Immune Checkpoint Inhibitors (ICI) in Metastatic Renal Cell Carcinoma
- ClinicalTrials.gov ID
- NCT04974671
- Acronym / sponsor ID
- 2000027702
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- 22 Dec 2023 (actual)
- Primary completion
- 1 Jan 2027 (estimated)
- Study completion
- 1 Apr 2028 (estimated)
- First posted
- 23 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Phase II trial will evaluate progression-free survival after Stereotactic Body Radiation Therapy to oligoprogressive (1-5) lesions in metastatic renal cell carcinoma patients on any immune checkpoint inhibitor-containing regimen with last dose of systemic therapy within 3 months prior to trial enrollment.
Detailed description
This Phase II trial will evaluate progression-free survival after Stereotactic Body Radiation Therapy to oligoprogressive (1-5) lesions in metastatic renal cell carcinoma patients on any immune checkpoint inhibitor-containing regimen with last dose of systemic therapy within 3 months prior to trial enrollment. Alternative local therapy (including but not limited to metastectomy or radiofrequency ablation) to one or more of the oligoprogressive lesions is allowed provided at least one of the lesions is receiving Stereotactic Body Radiation Therapy. Stereotactic Body Radiation Therapy will be delivered on nonconsecutive days (if >1 fraction) for a total of 1-5 fractions depending on anatomic site at the treating physicians discretion. Treatment to multiple sites can be delivered sequentially or concurrently, at the treating physicians discretion. Patients will undergo response-assessment imaging (CT chest/abdomen/pelvis with IV contrast and/or PET CT scan and/or MRI plus or minus contrast), and response to treatment will be measured via RECIST. The acute and long-term toxicity will be monitored and graded per CTCAE 5.0 (https://ctep.cancer.gov/). Patients will continue on the same immune checkpoint inhibitor-containing regimen during Stereotactic Body Radiation Therapy planning and delivery, and after completion of Stereotactic Body Radiation Therapy until progression of disease as defined by RECIST criteria. The immune checkpoint inhibitor-containing regimen can be continued beyond RECIST progression of disease if the treating physician feels that a patient will continue to benefit. Each eligible patient will be discussed at a multidisciplinary tumor board in the presence of medical and radiation oncology and will be seen in consultation in a Yale-affiliated radiation oncology department prior to enrollment in the trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Stereotactic Body Radiation Therapy | Experimental | Radiation: Stereotactic Body Radiation Therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Be willing and able to provide written informed consent/assent for the trial
- Be ≥ 18 years of age on day of signing informed consent.
- Have histologically confirmed renal cell carcinoma with metastatic disease detected on imaging. Biopsy of metastasis is preferred but not required
- The subject has a performance status of 0, 1, or 2 on the ECOG Performance Scale
- The life expectancy is > 6 months
Key exclusion criteria (14 listed)
- The subject must be excluded from participating in the trial if the subject
- Has had radiation therapy within 2 weeks of the first protocol treatment.
- Has brain-only oligoprogression. subjects with brain and systemic oligoprogression can still be considered, however treatment of brain metastases will be per standard of care prior to receiving study SBRT.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 2 weeks of the first protocol treatment. The use of lowdose steroids for management of chronic conditions is allowed (up to 12mg prednisone orally per day or the equivalent).
- Has had prior radiation therapy within 2 weeks of the first protocol treatment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Stereotactic Body Radiation Therapy1-5 fraction Stereotactic Body Radiation Therapy to all sites of progression | Radiation | Stereotactic Body Radiation Therapy |
Primary outcome
Progression Free Survival
Time frame: 6 Months
The primary objective of this study is to assess progression free survival after SBRT to all sites of progression and continuation of the same systemic regimen in patients with mRCC on ICI-containing systemic regimens with oligoprogression at 1-5 sites. Progression will be defined by RECIST criteria.
3 secondary outcomes
Recurrence
Time frame: Up to two years
Rate of Response
Time frame: Up to two years
Overall survival
Time frame: Up to two years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Kimberly Johung, MD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Stereotactic Body Radiation Therapy in people with Renal Cell Carcinoma and Metastatic Renal Cell Carcinoma, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Patricia Brand ((203) 738-9161, patricia.brand@yale.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (time frame: 6 Months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2025.