RECRUITING

Molecular Residual Disease (MRD) Guided Adjuvant ThErapy in Renal Cell Carcinoma (RCC)

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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

The goal of this Clinical Study is to understand the outcomes by informing therapy choice for adjuvant treatment in clear cell renal cell carcinoma by using molecular residual disease. The main question\[s\] it aims to answer are: * what is the progression free survival of a cohort of high risk resected RCC patients when treated based on MRD * what is the overall survival of high risk resected RCC patients when treated based on MRD Participants will forgo adjuvant therapy with pembrolizumab if they have no detectable molecular residual disease. Participants will continue on with standard of care pembrolizumab if they do appear to have molecular residual disease.

Official Title

Molecular Residual Disease (MRD) Guided Adjuvant ThErapy in Renal Cell Carcinoma (RCC)

Quick Facts

Study Start:2023-12-01

Study Completion:2025-06-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06005818

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
* Participants are eligible to be included in the study only if all the following criteria apply. 1. Must have histologically confirmed diagnosis of RCC with clear cell component with or without sarcomatoid features. Diagnosis of RCC with clear cell component is to be made by the investigator and does not require central histology review. 2. Patients must have at least ONE available assessment of molecular residual disease by the Signatera® (Natera Inc.) assay performed within the last 90 days prior to enrollment in study. 3. Be ≥18 years of age on the day of signing informed consent. 4. Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 5. Female participants of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 120 days after the last dose of study drug. 6. Male participants of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of trial therapy through 120 days after the last dose of study therapy. 7. The participant provides written informed consent for the trial. The participant may also provide consent for Future Biomedical Research; however, the participant may participate in the main trial without participating in Future Biomedical Research. 8. Have intermediate-high risk, high risk RCC as defined by the following pathological tumor-node-metastasis and Fuhrman grading status {Oza, 2022 #4431} 1. Intermediate-high risk RCC * pT2, Gr. 4 or sarcomatoid, N0, M0 * pT3, Any Gr., N0, M0 2. High risk RCC * pT4, Any Gr. N0, M0 * pT Any stage, Any Gr., N+, M0 9. Have received no prior systemic therapy for advanced RCC unless having recently initiated immunotherapy with pembrolizumab for no more than 6 weeks or 1 dose prior to enrollment. 10. Have undergone a partial nephroprotective or radical complete nephrectomy) 11. Must have undergone a nephrectomy ≥28 days prior to signing informed consent and ≤12 weeks prior to enrollment. 12. Must be tumor free as assessed by the investigator and validated by either CT or MRI scan of the brain and CAP ≤28 days from randomization. 13. Have an ECOG PS ≤2. 14. Have adequate organ function	* Medical Conditions 1. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment. 2. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. 3. Has a known additional malignancy that is progressing or required active treatment ≤3 years ago. Exceptions include early-stage cancers (carcinoma in situ or Stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, in situ prostate cancer, or in situ breast cancer that has undergone potentially curative therapy. 4. Has an active infection requiring systemic therapy. 5. Has a history of, or is currently on, dialysis. 6. Has a known history of human immunodeficiency virus infection. No human immunodeficiency virus testing is required unless mandated by local health authority. 7. Has a known active hepatitis B (hepatitis B surface antigen reactive) or HCV (eg, HCV RNA \[qualitative\] is detected). 8. Has a known history of active tuberculosis (Bacillus tuberculosis). 9. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator. 10. Has a known psychiatric or substance abuse disorder that would interfere with the cooperation with the requirements of the trial in the opinion of the investigator. 11. Has had a prior solid organ transplant. 12. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients (refer to Investigator's Brochure for further details on excipients). 13. A Woman of Childbearing Potential (WOCBP) who has a positive urine pregnancy test within 72 hours before randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Participants must be excluded/discontinued from the trial in the event of a positive or borderline positive test result. 14. 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 study treatment. 15. Has received prior anticancer therapy and not recovered from AEs due to previously administered agents. Note: denosumab may be allowed for bone protective purposes if dosing has been stable for ≥2 weeks before screening. 16. Has received a live vaccine within 30 days prior to the first dose of study treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. 17. Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.

Inclusion Criteria

Exclusion Criteria

* Participants are eligible to be included in the study only if all the following criteria apply.
1. Must have histologically confirmed diagnosis of RCC with clear cell component with or without sarcomatoid features. Diagnosis of RCC with clear cell component is to be made by the investigator and does not require central histology review.
2. Patients must have at least ONE available assessment of molecular residual disease by the Signatera® (Natera Inc.) assay performed within the last 90 days prior to enrollment in study.
3. Be ≥18 years of age on the day of signing informed consent.
4. Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
5. Female participants of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 120 days after the last dose of study drug.
6. Male participants of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of trial therapy through 120 days after the last dose of study therapy.
7. The participant provides written informed consent for the trial. The participant may also provide consent for Future Biomedical Research; however, the participant may participate in the main trial without participating in Future Biomedical Research.
8. Have intermediate-high risk, high risk RCC as defined by the following pathological tumor-node-metastasis and Fuhrman grading status {Oza, 2022 #4431}
1. Intermediate-high risk RCC
* pT2, Gr. 4 or sarcomatoid, N0, M0
* pT3, Any Gr., N0, M0
2. High risk RCC
* pT4, Any Gr. N0, M0
* pT Any stage, Any Gr., N+, M0
9. Have received no prior systemic therapy for advanced RCC unless having recently initiated immunotherapy with pembrolizumab for no more than 6 weeks or 1 dose prior to enrollment.
10. Have undergone a partial nephroprotective or radical complete nephrectomy)
11. Must have undergone a nephrectomy ≥28 days prior to signing informed consent and ≤12 weeks prior to enrollment.
12. Must be tumor free as assessed by the investigator and validated by either CT or MRI scan of the brain and CAP ≤28 days from randomization.
13. Have an ECOG PS ≤2.
14. Have adequate organ function

* Medical Conditions
1. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment.
2. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
3. Has a known additional malignancy that is progressing or required active treatment ≤3 years ago. Exceptions include early-stage cancers (carcinoma in situ or Stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, in situ prostate cancer, or in situ breast cancer that has undergone potentially curative therapy.
4. Has an active infection requiring systemic therapy.
5. Has a history of, or is currently on, dialysis.
6. Has a known history of human immunodeficiency virus infection. No human immunodeficiency virus testing is required unless mandated by local health authority.
7. Has a known active hepatitis B (hepatitis B surface antigen reactive) or HCV (eg, HCV RNA \[qualitative\] is detected).
8. Has a known history of active tuberculosis (Bacillus tuberculosis).
9. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
10. Has a known psychiatric or substance abuse disorder that would interfere with the cooperation with the requirements of the trial in the opinion of the investigator.
11. Has had a prior solid organ transplant.
12. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients (refer to Investigator's Brochure for further details on excipients).
13. A Woman of Childbearing Potential (WOCBP) who has a positive urine pregnancy test within 72 hours before randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Participants must be excluded/discontinued from the trial in the event of a positive or borderline positive test result.
14. 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 study treatment.
15. Has received prior anticancer therapy and not recovered from AEs due to previously administered agents. Note: denosumab may be allowed for bone protective purposes if dosing has been stable for ≥2 weeks before screening.
16. Has received a live vaccine within 30 days prior to the first dose of study treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
17. Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.

Contacts and Locations

Study Contact

Arnab Basu, MD,MPH

CONTACT

2059347636

abasu@uabmc.edu

Study Locations (Sites)

University of Alabama at Birmingham

Birmingham, Alabama, 35233

United States

Collaborators and Investigators

Sponsor: University of Alabama at Birmingham

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 Date2023-12-01

Study Completion Date2025-06-30

Study Record Updates

Study Start Date2023-12-01

Study Completion Date2025-06-30

Terms related to this study

Keywords Provided by Researchers

ADJUVANT

Additional Relevant MeSH Terms

Renal Cell Carcinoma