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

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.

Study Overview

• Status: Recruiting
• Conditions: Renal Cell Carcinoma; Metastatic Renal Cell Carcinoma; Oligoprogressive; Progression
• Intervention / Treatment: Radiation: Stereotactic Body Radiation Therapy

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 Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kwasi Boateng; Phone Number: 203-314-7948; Email: Kwasi.Boateng@yale.edu

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• In order to be eligible for participation in this trial, the subject must:

  1. Be willing and able to provide written informed consent/assent for the trial
  2. Be ≥ 18 years of age on day of signing informed consent.
  3. Have histologically confirmed renal cell carcinoma with metastatic disease detected on imaging. Biopsy of metastasis is preferred but not required
  4. The subject has a performance status of 0, 1, or 2 on the ECOG Performance Scale
  5. The life expectancy is > 6 months
  6. 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.

  7. 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

  8. There is no restriction on the total number of metastases
  9. Demonstrate adequate organ function as defined in Table 4, all screening labs should be performed within 28 days of protocol treatment
  10. 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.
  11. 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)
  12. 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.

Exclusion Criteria:

• The subject must be excluded from participating in the trial if the subject

  1. Has had radiation therapy within 2 weeks of the first protocol treatment.
  2. Is receiving TKI as part of their most recent systemic therapy regimen for their mRCC.
  3. 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.
  4. 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 low-dose steroids for management of chronic conditions is allowed (up to 12mg prednisone orally per day or the equivalent).
  5. Has had prior radiation therapy within 2 weeks of the first protocol treatment.
  6. 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.
  7. 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.
  8. Has a history of (non-infectious) pneumonitis that required steroids, current pneumonitis or evidence of interstitial lung disease.
  9. Has an active infection requiring systemic therapy.
  10. 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.
  11. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  12. Has received a live vaccine within 30 days prior to the first protocol treatment.
  13. Has serious medical comorbidities precluding radiotherapy. These include subjects with lung metastases with interstitial lung disease, connective tissue diseases such as lupus or scleroderma, Crohn's disease in subjects where the GI tract will receive radiation
  14. Substantial overlap with a previously treated radiation volume. Prior radiotherapy is allowed as long as the composite plan meets dose constraints

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stereotactic Body Radiation Therapy	Radiation: Stereotactic Body Radiation Therapy; 1-5 fraction Stereotactic Body Radiation Therapy to all sites of progression

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence	Imaging will be done every three months to determine rate of recurrence.	Up to two years
Rate of Response	To determine rate of response at non-treated sites. Imaging will be done every three months.	Up to two years
Overall survival	Overall survival will be assessed up to two years	Up to two years

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Principal Investigator: Kimberly Johung, MD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2022
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: July 13, 2021
• First Submitted That Met QC Criteria: July 14, 2021
• First Posted (Actual): July 23, 2021

Study Record Updates

• Last Update Posted (Actual): November 8, 2023
• Last Update Submitted That Met QC Criteria: November 6, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma, Renal Cell; Carcinoma
• Other Study ID Numbers: 2000027702; No NIH funding (Other Identifier: 11.16.23)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No