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

A Single-center, Non-randomized Controlled, Single-arm, Phase II Clinical Trial of Pembrolizumab and Axitinib as Neoadjuvant Therapy for Locally Advanced Non-metastatic Clear Cell Renal Cell Carcinoma

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Renal Cell Carcinoma; Clear Cell Renal Cell Carcinoma
• Intervention / Treatment: Drug: Axitinib; Drug: Pembrolizumab

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Bin HUO; Phone Number: 6610 +860228832; Email: huobin_doctor@icloud.com

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300211
      • Tianjin Medical Unversity Second Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Locally Advanced Non-metastatic Clear Cell Renal Cell Carcinoma; Neoadjuvant pembrolizumab plus axitinib	Drug: Axitinib; Tyrosine kinase inhibitor，licensed for use in treatment of renal cell carcinoma. Oral treatment Axitinib given 5 mg PO BID.; Other Names: Inlyta; Drug: Pembrolizumab; PD-1 inhibitor，Pembrolizumab 200mg IV, every 3 weeks.; Other Names: Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Pathologic Response (MPR)	The residual tumor cells (% RVT) were calculated according to immune related pathologic response criteria (irPRC), MPR is defined as %RVT<10%	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic Complete Response (pCR)	The residual tumor cells (% RVT) were calculated according to immune related pathologic response criteria (irPRC), pCR is defined as %RVT<0%	12 weeks
Objective response rate (ORR)	Rate of patients achieving a complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) and immune-related response criteria (IRC)	12 weeks
Disease-free survival(DFS)	DFS is defined as the time from treatment to recurrence of tumor or death	Up to 24 months
Overall survival(OS)	OS is defined as the time from treatment to death	Up to 24 months
Incidence of treatment-related adverse events(AEs)	To be assessed by CTCAE v5.0	Up to 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarker analysis	Paired t-test or Wilcoxon singed-rank test will be used to compare the biomarkers change before, during, and after treatment.	Up to 24 months

Collaborators and Investigators

• Sponsor: Tianjin Medical University Second Hospital
• Investigators: Principal Investigator: Bin HUO, MD, Tianjin Medical University Second Hospital; Principal Investigator: Gang LI, MD, Tianjin Medical University Second Hospital; Study Director: Haitao WANG, Professor, Tianjin Medical University Second Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): August 20, 2021
• Primary Completion (Anticipated): August 20, 2022
• Study Completion (Anticipated): August 20, 2023

Study Registration Dates

• First Submitted: July 30, 2021
• First Submitted That Met QC Criteria: July 30, 2021
• First Posted (Actual): August 6, 2021

Study Record Updates

• Last Update Posted (Actual): August 6, 2021
• Last Update Submitted That Met QC Criteria: July 30, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Pembrolizumab; Neoadjuvant; Axitinib
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Pembrolizumab; Axitinib
• Other Study ID Numbers: PANDORA 001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes