RECRUITING

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

Conditions

Renal Cell Carcinoma Metastatic Renal Cell Carcinoma Oligoprogressive Progression

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

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.

Official Title

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

Quick Facts

Study Start:2022-08-08

Study Completion:2027-04-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04974671

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	* 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

Inclusion Criteria

Exclusion 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.

* 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

Contacts and Locations

Study Contact

Jialing Zhang, PhD

CONTACT

475-234-9684

jialing.zhang@yale.edu

Principal Investigator

Kimberly Johung, MD

PRINCIPAL_INVESTIGATOR

Yale University

Study Locations (Sites)

Yale University

New Haven, Connecticut, 06520

United States

Collaborators and Investigators

Sponsor: Yale University

Kimberly Johung, MD, PRINCIPAL_INVESTIGATOR, Yale University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-08-08

Study Completion Date2027-04-01

Study Record Updates

Study Start Date2022-08-08

Study Completion Date2027-04-01

Terms related to this study

Additional Relevant MeSH Terms

Renal Cell Carcinoma
Metastatic Renal Cell Carcinoma
Oligoprogressive
Progression