Trial Of Stereotactic Body Radiation Therapy (SBRT) for Oligoprogression on Immune Checkpoint Inhibitors (ICI) in Metastatic Renal Cell Carcinoma

NCT04974671 | Recruiting Phase 2

• 2 other identifiers: 2000027702No NIH funding
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Oligoprogressive; Renal Cell Carcinoma; Metastatic Renal Cell Carcinoma; Progression

Outcome Measures

Primary Outcomes (1)

• 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.

  6 Months

Secondary Outcomes (3)

• Recurrence

  Up to two years

• Rate of Response

  Up to two years

• Overall survival

  Up to two years

Study Arms (1)

Stereotactic Body Radiation Therapy

EXPERIMENTAL

Radiation: Stereotactic Body Radiation Therapy

Interventions

Stereotactic Body Radiation Therapy RADIATION

1-5 fraction Stereotactic Body Radiation Therapy to all sites of progression

Stereotactic Body Radiation Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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:
• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

Yale University

New Haven, Connecticut, 06520, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Renal Cell; Disease Progression

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Kimberly Johung, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Patricia Brand

CONTACT

(203) 738-9161; patricia.brand@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2021
• First Posted: July 23, 2021
• Study Start: December 22, 2023
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: December 4, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)