Multimodal radiotherapy for advanced renal cell carcinoma after immunotherapy

An Open-label, Single-arm Study to Evaluate the Efficacy and Safety of Multimodal Radiotherapy in the Treatment of Renal Cell Carcinoma Progressed After Prior Immunotherapy

This study is testing whether combining different types of radiation therapy with ongoing treatment can help people with advanced kidney cancer who haven't responded well to previous immunotherapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 35 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Jinling Hospital, China (Academic / other)
• Drugs / interventions: immunotherapy, radiation
• Locations: 1 site (Nanjing, Jiangsu)
• Trial ID: NCT06255223 on ClinicalTrials.gov

What this trial studies

This clinical study aims to evaluate the effectiveness and safety of multimodal radiotherapy in patients with advanced renal cell carcinoma (RCC) who have experienced disease progression after prior immunotherapy. Eligible participants will have undergone 1-2 systemic therapies, including immune checkpoint inhibitors, and will receive high-dose or low-dose radiotherapy in conjunction with their ongoing treatment. The study will assess the disease control rate and monitor safety outcomes to determine the potential benefits of this combined approach.

Who should consider this trial

Good fit: Ideal candidates include patients with histologically confirmed advanced renal cell carcinoma who have progressed after 1-2 systemic therapies and have multiple metastases.

Not a fit: Patients who have not received prior immunotherapy or those with ECOG performance status greater than 1 may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve disease control and outcomes for patients with advanced RCC who have limited options after immunotherapy.

How similar studies have performed: While multimodal approaches in cancer treatment have shown promise, this specific combination of radiotherapy and immunotherapy in RCC is relatively novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

* Renal cell carcinoma confirmed histologically or cytopathologically, including unresectable or recurrent metastatic renal cell carcinoma.
* Subject's previous treatment: Disease progression or intolerance following prior treatment with 1-2 systemic therapies (at least one regimen containing immune checkpoint inhibitors, including combined VEGFR-TKI drugs), And patients who have progressed within 12 months of prior immunoadjuvant or neoadjuvant therapy; According to the evaluation of attending physicians and professional radiotherapy doctors, it meets the standard of radiotherapy.
* Patients can tolerate sequential immunotherapy while receiving radiation therapy.
* At least two or more metastases at different sites are considered observable according to RECIST v1.1.
* Subjects have fully understood and voluntarily signed an informed Consent form (ICF).
* ECOG 0-1 points.
* Major organs are functioning well.
* Willing and able to comply with study plan visits, treatment laboratory tests, sample retention, and other procedures.
* Fertile women must voluntarily use a highly effective contraceptive method (e.g., oral, injectable or implantable, barrier method, spermicide and condom, or intrauterine device) from the study period to ≥120 days after the last dose and have negative urine or serum pregnancy test results ≤7 days prior to enrolment.
* Male patients who are not sterilized must voluntarily use highly effective contraception during the study period until ≥120 days after the last dose.

Exclusion Criteria:

* A history of malignancies other than the disease studied within the past 5 years, other than malignancies that are expected to be cured with treatment (including but not limited to adequately treated thyroid cancer, cervical carcinoma in situ, basal or squamous cell skin cancer, or breast ductal carcinoma in situ treated with radical surgery).
* Systemic treatment with other antitumor agents, including targeted agents, immunotherapy agents and their combination regimens (eligible for inclusion after 5 half-lives), local antitumor therapy, or clinical investigational drug or device therapy, was administered 4 weeks prior to the first study.
* Previous history of radiation therapy at any site or in any mode.
* Had major surgery (as judged by the investigator) within 4 weeks prior to the first trial or was convalescing.
* A history of severe drug allergy, including but not limited to antibody drugs.
* Patients with contraindications to restart immunotherapy.
* A known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation may require long-term adrenal corticosteroid therapy.
* Patients with thyroid, suprarenal, or hypopituitarism that can be controlled with hormone replacement therapy alone, type 1 diabetes, and psoriasis or vitiligo that do not require systemic treatment are eligible to participate in this study.
* Toxicity did not resolve after previous antitumor therapy, i.e. regression to baseline, prescribed grade 0 to 1 (except alopecia) as defined in NCI-CTCAE 5.0, or to the levels specified in the inclusion/exclusion criteria. Irreversible toxicity (such as hearing loss) that could reasonably be expected not to be aggravated by the drug under study could be included in this study.
* Have central nervous system metastases and/or cancerous meningitis.
* A known history of clinically significant liver disease.
* Accompanied by uncontrolled third space effusion requiring repeated drainage, such as pleural effusion, ascites, pericardial effusion, etc.
* In the first study, systemic corticosteroids or other immunosuppressive drugs were administered within 14 days prior to medication.
* Patients with any severe or uncontrolled disease.
* Have or have a suspected presence of active autoimmune diseases, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, etc.
* Renal failure requires hemodialysis or peritoneal dialysis.
* A history of immunodeficiency, including HIV positive or other acquired, congenital immunodeficiency diseases, or a history of organ transplantation.
* History of live attenuated vaccine vaccination within 4 weeks prior to administration or expected live attenuated vaccine vaccination during the study period was studied for the first time.
* People who have a history of psychotropic substance abuse and cannot abstain or have a history of mental disorders.
* Pregnant or lactating women.
* Other severe, acute, or chronic medical or psychiatric conditions or laboratory abnormalities, as determined by the investigator, that may increase the risks associated with study participation or that may interfere with the interpretation of the study results.

Where this trial is running

Nanjing, Jiangsu

• Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University — Nanjing, Jiangsu, China (Recruiting)

Study contacts

• Study coordinator: Le Qu, M. D.

Conditions Renal Cell Carcinoma; Radiotherapy; Immune Checkpoint Inhibitor; RCC; Multimodal radiotherapy