Pembrolizumab and Axitinib as Neoadjuvant Therapy for Locally Advanced Non-metastatic Clear Cell Renal Cell Carcinoma (PANDORA)

Tianjin Medical University Second Hospital

Status and phase

Unknown

Phase 2

Conditions

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Treatments

Drug: Axitinib

Drug: Pembrolizumab

Study type

Interventional

Funder types

Other

Identifiers

NCT04995016

PANDORA 001

Details and patient eligibility

About

This is a single-arm phase II clinical trial to evaluate the initial efficacy and safety of pembrolizumab combined with axitinib as neoadjuvant therapy for locally advanced non-metastatic clear cell renal cell carcinoma.

Full description

This study is design to prospectively investigate the safety and efficacy of pembrolizumab combined with axitinib in downsizing tumors in patients with nonmetastatic biopsy-proven clear cell renal cell carcinoma. This is a single-institution, single-arm phase 2 clinical trial. Patients will receive axitinib 5 mg bid on days 1-21 combined with pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatments repeat every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.Patients then will receive partial or radical nephrectomy after neoadjuvant therapy.

Enrollment

18 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients with a renal mass consistent with a clinical stage >= T3Nx or TanyN+ or deemed unresectable by surgeon
Renal cell carcinoma with clear cell component on pre-treatment biopsy of the primary tumor
The participant (or legally acceptable representative if applicable) provides written informed consent and the willingness and ability to comply with all aspects of the protocol
Have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2
Agree to collect tumor tissue, blood and other specimens required by this study and apply them to relevant studies
Important organs and bone marrow functions meet the following requirements: absolute neutrophil count (ANC) ≥1.5×10^9/L, platelet (PLT) ≥100×10^9/L, hemoglobin (HGB) ≥9g/dL;Liver function: serum total bilirubin (TBIL) ≤1.5 times normal upper limit (ULN), alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤2.5 times ULN, serum albumin (ALB) ≥ 2.8g /dL. Renal function: serum creatinine (Cr) ≤1.5×ULN, or creatinine clearance ≥40 mL/min
Cardiac function met the following conditions: baseline electrocardiogram (ECG) had no evidence of PR prolongation or AV block
All females must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of beta-human chorionic gonadotropin [beta-hCG]) at the screening visit and the baseline visit. A pregnancy test needs to be performed within 72 hours of the first dose of study drug. Women of childbearing potential (WOCBP) must agree to use a highly effective method of contraception for the entire study period and for 120 days after study discontinuation
Male subjects who are partners of women of childbearing potential must use a condom and their female partners of childbearing potential must use a highly effective method of contraception beginning at least 1 menstrual cycle prior to starting study drugs, throughout the entire study period, and for 120 days after the last dose of study drug, unless the male subjects are totally sexually abstinent or have undergone a successful vasectomy with confirmed azoospermia or unless the female partners have been sterilized surgically or are otherwise proven sterile

Exclusion criteria

Subject has an active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents
Subject is currently participating or has participated in a study of an investigational agent or using an investigational device within 30 days of the first dose of study treatment
Subject is expected to require any other form of systemic or localized antineoplastic therapy while on study
Subject is on any systemic steroid therapy, within one week before the planned date for first dose of study treatment.
Subject is on any other form of immunosuppressive medication
Unable to swallow and retain orally administered medication
Active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other -Gastrointestinal conditions with increased risk of perforation; history of abdominal fistula, GI perforation, or intra-abdominal abscess within 4 weeks before beginning study treatment
Known history of HIV infection or a known history of or is positive for Hepatitis B or Hepatitis C
Presence of active infection requiring systemic therapy
Corrected QT interval duration prolongation
History of any one or more of the following cardiac conditions within the past 6 months: Cardiac angioplasty or stenting; Myocardial infarction; Unstable angina; --History of Class III or IV congestive heart failure according to New York Heart Association classification
History of cerebrovascular accident within the past 6 months
Poorly controlled hypertension
History of untreated deep venous thrombosis
Presence of any non-healing wound, fracture, or ulcer, or presence of symptomatic peripheral vascular disease
Evidence of bleeding diathesis or coagulopathy
Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures
Has taken any prohibited medications that are listed in the protocol within 14 days of the first dose of study treatment
Subject has received or will receive a live vaccine within 30 days before the first administration of study treatment