Molecular Residual Disease (MRD) Guided Adjuvant ThErapy in Renal Cell Carcinoma (RCC)
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab injection
- Conditions
- Renal Cell Carcinoma
- Sponsor
- University of Alabama at Birmingham
- Enrollment
- 100
- Locations
- 1
- Primary Endpoint
- Disease Free Survival (DFS) by Investigator's assessment as defined by RECIST 1.1
- Status
- Recruiting
- Last Updated
- 6 months ago
Overview
Brief Summary
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.
Detailed Description
This is a multicenter open label biomarker integral treatment de-escalation study, where patients with localized renal cell carcinoma who are otherwise eligible to receive standard of care pembrolizumab will be offered observation only, if they do not demonstrate presence of molecular residual disease. Primary Objective(s): Provide an estimate for the 1 year -Disease-Free Survival (DFS) Provide an estimate for overall Survival (OS) for patients treated based on MRD information. Estimate the safety of an MRD based strategy of adjuvant therapy in RCC Primary Endpoint(s) : i. Disease Free Survival (DFS) by Investigator's assessment as defined by RECIST 1.1 Secondary Endpoint: i. Overall Survival at 1 year from surgery ii. Safety as defined by incidence of adverse events per NCI CTCAE v5.0 100 patients with non-metastatic clear cell renal cell carcinoma who undergo surgery to remove tumor will be enrolled, patients will be adults (≥18 years), there are no gender, age, demographic group related constraints, the trial will be conducted at centers based in the United States.
Investigators
Charles Peyton
Assistant Professor
University of Alabama at Birmingham
Eligibility Criteria
Inclusion Criteria
- •Participants are eligible to be included in the study only if all the following criteria apply.
- •Type of Participant and Disease Characteristics
- •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.
- •Molecular Residual Disease
- •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.
- •Demographics
- •Be ≥18 years of age on the day of signing informed consent.
- •Female Participants:
- •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.
- •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.
Exclusion Criteria
- •Medical Conditions
- •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.
- •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.
- •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.
- •Has an active infection requiring systemic therapy.
- •Has a history of, or is currently on, dialysis.
- •Has a known history of human immunodeficiency virus infection. No human immunodeficiency virus testing is required unless mandated by local health authority.
- •Has a known active hepatitis B (hepatitis B surface antigen reactive) or HCV (eg, HCV RNA \[qualitative\] is detected).
- •Has a known history of active tuberculosis (Bacillus tuberculosis).
- •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.
Arms & Interventions
Arm 2 MRD positive patients
Patients are treated with Pembrolizumab 400 mg IV q 6 weeks for a total of 1 year
Intervention: Pembrolizumab injection
Outcomes
Primary Outcomes
Disease Free Survival (DFS) by Investigator's assessment as defined by RECIST 1.1
Time Frame: 1 year from surgery
Secondary Outcomes
- Overall Survival (OS)(1 year from surgery)