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

NCT04995016 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: PANDORA 001
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Renal Cell Carcinoma; Clear Cell Renal Cell Carcinoma

Keywords

Pembrolizumab; Axitinib; Neoadjuvant

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Pathologic Complete Response (pCR)

  12 weeks

• Objective response rate (ORR)

  12 weeks

• Disease-free survival(DFS)

  Up to 24 months

• Overall survival(OS)

  Up to 24 months

• Incidence of treatment-related adverse events(AEs)

  Up to 24 months

Other Outcomes (1)

• Biomarker analysis

  Up to 24 months

Study Arms (1)

Locally Advanced Non-metastatic Clear Cell Renal Cell Carcinoma

EXPERIMENTAL

Neoadjuvant pembrolizumab plus axitinib

Drug: Pembrolizumab; Drug: Axitinib

Interventions

Pembrolizumab DRUG

PD-1 inhibitor，Pembrolizumab 200mg IV, every 3 weeks.

Also known as: Keytruda

Locally Advanced Non-metastatic Clear Cell Renal Cell Carcinoma

Axitinib DRUG

Tyrosine kinase inhibitor，licensed for use in treatment of renal cell carcinoma. Oral treatment Axitinib given 5 mg PO BID.

Also known as: Inlyta

Locally Advanced Non-metastatic Clear Cell Renal Cell Carcinoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Tianjin Medical University Second Hospital: lead

Study Sites (1)

Tianjin Medical Unversity Second Hospital

Tianjin, Tianjin Municipality, 300211, China

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

pembrolizumab; Axitinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Bin HUO, MD

  Tianjin Medical University Second Hospital

  PRINCIPAL INVESTIGATOR

• Gang LI, MD

  Tianjin Medical University Second Hospital

  PRINCIPAL INVESTIGATOR

• Haitao WANG, Professor

  Tianjin Medical University Second Hospital

  STUDY DIRECTOR

Central Study Contacts

Bin HUO

CONTACT

+860228832; huobin_doctor@icloud.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: simon's two stage design

Study Record Dates

• First Submitted: July 30, 2021
• First Posted: August 6, 2021
• Study Start: August 20, 2021
• Primary Completion: August 20, 2022
• Study Completion: August 20, 2023
• Last Updated: August 6, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)