Autologous Dendritic Cell Vaccine in Kidney Cancer

NCT05127824 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCC 19-126
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to estimate the probability of immune response for the combination treatment of dendritic cell vaccine with oral cabozantinib and characterize the safety profile of interventional therapy.

Conditions

Carcinoma, Renal Cell

Keywords

Clear Cell Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (4)

• Probability of immune response

  Proportion of HLA-A2+ ccRCC patients that exhibit improved peripheral blood CD8+ T cell responses against 3 or more vaccine-inclusive peptide epitopes (DLK1, EphA2, HBB, NRP1, RGS5, TEM1) after active vaccination with Type I-polarized autologous dendritic cell (αDC1) vaccine with concomitant oral cabozantinib (IFN-γ ELISPOT).

  Up to 48 months

• Safety profile of interventional therapy - Adverse Events

  Proportion of patient reported symptoms and Dose Limiting Toxicities (DLT) for specific adverse events per NCI CTCAE v5.0.

  Up to 48 months

• Safety profile of interventional therapy - reduction in CD31+

  Proportion of RCC patients that exhibit greater than 30% reduction in CD31+ blood vessel content from baseline biopsy.

  Up to 48 months

• Reduction in tumor vascularity

  Proportion of RCC patients that exhibit greater than 30% reduction in CD31+ blood vessel content from baseline biopsy.

  Baseline; Up to 48 months

Secondary Outcomes (1)

• Markers of vascular normalization

  Baseline; Up to 48 months

Other Outcomes (8)

• To assess the impact of treatment on formation of tertiary lymphoid structures in pre-treatment biopsies and treated tumors.

  48 months

• To assess peripheral blood CD8+ T cells longitudinally for reactivity against alternate peptide epitopes of DLK1, EphA2, HBB, NRP1, RGS5, TEM1 or against non-vaccine-related RCC-associated antigens

  48 months

• To assess immune cell composition and "fitness" within vs. outside of tumor-associated TLS

  48 months

Study Arms (2)

HLA-A2 postive

EXPERIMENTAL

The study will include 21 participants over the 18 years of age with newly diagnosed, clinically localized clear cell renal cell carcinoma, planned for surgical resection with curative intent. Participants receiving vaccine much be HLA-A2 positive.

Biological: Autologous alpha-DC1/TBVA vaccine; Drug: Cabozantinib

HLA-A2 negative

ACTIVE COMPARATOR

Up to 21 additional participants who screen as HLA-A2 negative will be enrolled as non-treatment controls. These participants will not be required to undergo blood collection or study procedures

Drug: Cabozantinib

Interventions

Autologous alpha-DC1/TBVA vaccine BIOLOGICAL

Dendritic cells (DC) are derived from autologous (the subject's own) mononuclear cells in the peripheral blood obtained from the PRBC. In this case, "biologic product" and "biologic substance" are the same. The vaccine will be manufactured in the HCC-IMPCL, under cGMP conditions.

HLA-A2 postive

Cabozantinib DRUG

Cabozantinib tablets are supplied as film coated tablets containing cabozantinib malate equivalent to 20 mg and 60 mg of cabozantinib and contain microcrystalline cellulose, lactose anhydrous, hydoxypropyl cellulose, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate and Opadry® yellow. The 60 mg tablets are oval and the 20 mg tablets are round. Doses of 40 mg will comprise two 20-mg tablets.

Also known as: Cometriq, Cabometyx

HLA-A2 negative; HLA-A2 postive

Eligibility Criteria

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

You may qualify if:

• Histologically proven clear cell renal cancer that is non-metastatic and amenable to surgical resection with no evidence of metastatic disease or lesions outside of the kidney.
• years or older (male or female) with an ECOG performance status of 0 or 1.
• Have serotype HLA-A2+ if receiving vaccine.
• Capable of understanding and complying with the protocol requirements and have signed the informed consent document.
• Adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 14 days before first dose of study treatment:
• Absolute neutrophil count (ANC) ≥ 1500/µL without granulocyte colony- stimulating factor support.
• White blood cell count ≥ 2500/µL.
• Platelets ≥ 100,000/µL without transfusion.
• Hemoglobin ≥ 9 g/dL (≥ 90 g/L).
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 3x upper limit of normal (ULN). ALP ≤ 5x ULN with documented bone metastases.
• Total bilirubin ≤ 1.5x ULN (for subjects with Gilbert's disease ≤ 3x ULN).
• Serum albumin ≥ 2.8 g/dl
• (PT)/INR or partial thromboplastin time (PTT) test \< 1.3x the laboratory ULN
• Serum creatinine ≤ 2.0 ULN or calculated creatinine clearance ≥ 30 mL/min (≥ 0.5 mL/sec) using the Cockcroft-Gault equation: Males: (140 - age) x weight (kg)/(serum creatinine \[mg/dL\] × 72) Females: \[(140 - age) x weight (kg)/(serum creatinine \[mg/dL\] × 72)\] × 0.85
• Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol), or 24-h urine protein ≤ 1

You may not qualify if:

• Current (within the preceding 6 weeks) treatment with systemic immunosuppressive agents including steroids except when they are administered as replacement therapy for endocrine dysfunction and do not exceed 10 mg prednisone or equivalent daily.
• Known or suspected metastatic disease.
• Active Hepatitis B or Hepatitis C infection or any other active infection requiring intravenous therapy.
• Blood transfusion within two weeks prior to leukapheresis.
• Prior treatment with cabozantinib.
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within two weeks before first dose of study treatment.
• Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within four weeks before first dose of study treatment.
• Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
• Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:
• Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
• Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
• Prothrombin time (PT/INR) or partial thromboplastin time (PTT) test ≥ 1.3 X the laboratory ULN within 7 days before the first dose of study treatment.
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• a. Cardiovascular disorders: i. Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
• ii. Uncontrolled hypertension defined as sustained blood pressure (BP) \> 140 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment.

Sponsors & Collaborators

• Jodi Maranchie: lead

Study Sites (1)

UPMC Department of Urology

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

Related Publications (1)

• Tannir NM, Pal SK, Atkins MB. Second-Line Treatment Landscape for Renal Cell Carcinoma: A Comprehensive Review. Oncologist. 2018 May;23(5):540-555. doi: 10.1634/theoncologist.2017-0534. Epub 2018 Feb 27.

  PMID: 29487224 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

cabozantinib

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

Study Officials

• Jodi Maranchie, MD

  UPMC Department of Urology

  PRINCIPAL INVESTIGATOR

• Walter Storkus, PhD

  University of Pittsburgh

  STUDY DIRECTOR

Central Study Contacts

Morgan Pokora, RN

CONTACT

412-623-4886; pokoraml3@upmc.edu

Jodi Maranchie, MD

CONTACT

412-605-3019; maranchijk@upmc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor Urology & Urologic Oncology

Study Record Dates

• First Submitted: October 22, 2021
• First Posted: November 19, 2021
• Study Start: July 6, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 4, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)