Multi-classifier System for Stratifying Stage III Papillary Renal Cell Carcinoma of Receiving Adjuvant Therapy

Sun Yat-sen University

Status and phase: Not yet enrolling; Phase 3

Conditions: Papillary Renal Cell Carcinoma

Treatments: Drug: Placebo; Drug: Pembrolizumab

Study type: Interventional

Funder types: Other

Identifiers

NCT06146777

FirstSunYatSen20231101

Details and patient eligibility

About

The goal of this trial is to test whether patients with stage III papillary renal cell carcinoma (pRCC) could benefit from adjuvant therapy or not. The investigators invented a multi-classifier system that was successfully categorise patients with stage III pRCC into high-risk and low-risk groups. Here the investigators randomly assign classifier-defined high risk patients of stage III pRCC into adjuvant pembrolizumab group placebo group. Disease-free survival and overall survival are the end points of observation.

Full description

kidney cancer represented 4.2% of all new cancer cases, and its incidence has been increasing. Over 90% of kidney cancer cases are renal cell carcinoma (RCC), which includes various subtypes with distinct histologic features, clinical courses, and responses to therapy. Clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) are the most common histologic subtypes of RCC, accounting for approximately 75% and 20% of all cases, respectively. Adjuvant pembrolizumab showed promising efficacy in ccRCC, however, whether high-risk pRCC patients could benefit from adjuvant pembrolizumab remain unknown.

Participants will be assigned to continue with the study treatment until any of the following occurs: the recurrence of the disease; the emergence of unacceptable adverse events (AEs); the presence of an intercurrent illness that precludes further administration of the treatment; the decision of the Investigator to withdraw the participant; noncompliance with the study treatment or procedural mandates; administrative reasons necessitating the discontinuation of treatment; or the completion of 17 treatment cycles (approximately one year), with each cycle 3 weeks long.

Enrollment: 468 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histological confirmation of pRCC
• With confirmed diagnosis of stage III pRCC
• Classified as high-risk by multi-classifier system
• With moderate/good Eastern Cooperative Oncology Group (ECOG) health rating (PS): 0-1 score.
• Receive radical operation for renal cancer with negative margin.
• Receive no anti-cancer treatment before primary surgery.
• The informed consent has been obtained from the patient.

Exclusion criteria

• Patients with Transcription factor enhancer 3(TFE3) or transcription factor EB (TFEB) translocation proven by cytogenetic analysis or by fluorescence in situ hybridization (FISH)
• Previously received neoadjuvant therapy
• With severe comorbidities, such as cardiovascular disease, chronic obstructive pulmonary disease, diabetes mellitus, and chronic renal dysfunction.
• With bad compliance or contraindication to enrollment.
• Pregnant woman or lactating woman.
• With contraindication to receive pembrolizumab, such as had a prior solid organ transplant, has a known history of human immunodeficiency virus infection.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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468 participants in 2 patient groups, including a placebo group

Pembrolizumab

Experimental group

Description:

Participants receive pembrolizumab 200 mg on Day 1 of each 3-week cycle for up to 17 cycles.

Treatment:

Drug: Pembrolizumab

Placebo

Placebo Comparator group

Description:

Participants receive intravenous placebo on Day 1 of each 3-week cycle for up to 17 cycles.

Treatment:

Drug: Placebo