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Autologous Dendritic Cell Vaccine in Kidney Cancer

ConditionCarcinoma, Renal Cell
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorJodi Maranchie

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

18 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.

Disqualifiers

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.

Trial design

Design model

Single group

Treatments tested in this trial

  • Autologous alpha-DC1/TBVA vaccine

    Biological/Vaccine

    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.

  • 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.

Treatment groups

42 Participants
are divided into 2 treatment groups
Group A: HLA-A2 postiveExperimental treatment 2 interventions
Group B: HLA-A2 negativeActive comparator 1 intervention

Trial outcomes

Primary outcomes

1

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).

Time frame
Up to 48 months
2

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.

Time frame
Up to 48 months
3

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.

Time frame
Up to 48 months
4

Reduction in tumor vascularity

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

Time frame
Baseline; Up to 48 months

Secondary outcomes

1

Markers of vascular normalization

Change in presence of mature CD31+ (HES1+) blood vessels with tightly approximated abluminal SMA+ pericytes and the lack of immature CD31+ blood vessels with loosely-approximated NG2+ pericytes before and after treatment.

Time frame
Baseline; Up to 48 months

Other outcomes

1

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

Number of TLS before and after treatment, identified by landmark expression of MECA-79/PNAd+ high endothelial venules with proximal aggregates of DC-LAMP+ DC and CD3+ T cells and quantified using a Euclidean Displacement imaging algorithm.

Time frame
48 months
2

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

Proportion of cells with specific CD8+ T cell reactivity against peptides derived from other TBVA or RCC-associated antigens that were not included in the vaccine (as an index of epitope spreading in the patient's T cell repertoire).

Time frame
48 months
3

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

Change in number and classification of T cell repertoire before and after treatment, longitudinally, and within TLS vs. outside TLS of the same sample by flow cytometry/TCRBseq.

Time frame
48 months
4

To assess TCRA/B repertoire evenness (oligoclonality), convergence (antigenic focus) and compartmentalization (tumor vs. blood) in patients at baseline vs. on treatment

Changes in TCRseq adaptome analysis of CD8+ MACS T cells from tumor/PBMC after treatment.

Time frame
48 months

Sponsors and contacts

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Jodi Maranchie

Lead sponsor

University of Pittsburgh

Sponsor institution

Source ClinicalTrials.gov
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