Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Symptoms and General Pathology

Prostatic Neoplasms

Neoplasm Metastasis

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Pembrolizumab

Antibodies

Cyclophosphamide

Immune Checkpoint Inhibitors

Immunomodulating Agents

Ipilimumab

Immunoglobulins

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Patients with castration resistant prostate cancer and imaging proven metastases will be treated by autologous dendritic cell based cryoimmunotherapy of the prostatic tumor tissue assisted by immunomodulation consisting of low-dose metronomic cyclophosphamide for all patients plus ipilimumab for the latter half of all patients.

Update January 2019: The protocol was changed as approved by the Norwegian Medicines Agency and the Regional Ethical Committee in Western Norway for the 3 last patients of altogether 18 patients. Consequently, the 3 last patients received 200 mg i.v. of pembrolizumab (and no ipilimumab) post-CryoIT.

Autologous dendritic cells will be obtained following leukapheresis and cytokine induction and will be injected into cryoablated prostate cancer tissue under ultrasound guidance.

Dendritic cell based cryoimmunotherapy

Low-dose cyclophosphamide will be given metronomically for the purpose of selective inhibition of T regulatory cells for 6 months following start of treatment.

The antibody and immune checkpoint inhibitor ipilimumab (Yervoy) will be given for the last 10 patients enrolled into the study in addition to cryoimmunotherapy and low-dose cyclophosphamide.

ipilimumab

Christian Beisland, MD PhD

20 patients with invasive castration resistant prostate cancer and radiologically verified metastases will be enrolled into the Phase I Clinical Trial. The trial is a dendritic cell based immunotherapy. Autologous dendritic cells will be obtained by leukapheresis and elutriation and stimulation by cytokines. The induced dendritic cells will have to pass viability, immunophenotyping and sterility criteria and will be injected into a cryoablated region of the primary prostate cancer tumor. The treatment is supplemented by immunomodulatory regimens.

The study treatment dendritic cells (ACT2001) will be injected into the prostate following prostatic cryoablation. It is speculated that antigen from the cryoablated cancer will be available in the vicinity of the cryoablation field immediately following the procedure. Autologous, immature dendritic cells are capable of internalizing antigen, migrating to the lymphatic system, and presenting antigenic epitopes to T lymphocytes. In this way, dendritic cells are capable of initiating a cell-mediated systemic immune response.

In concept, the cancer itself should provide a specific and potentially broad spectrum of cancer-related antigens. Regulatory T lymphocytes, which have been implicated in dampening or halting cell-mediated, antigen-specific immune responses, will be selectively depleted using a regimen of low-dose cyclophosphamide. Low-dose cyclophosphamide has been empirically shown to selectively deplete the number of circulating regulatory T cells. The second half of patients will in addition receive treatment with the the immune checkpoint inhibitor ipilimumab antibody as one additional measure to avoid cancer cell immune evasion.

Using this combination of therapies, it is thought that a clinically significant anti-cancer immune response might be elicited.

Phase I Clinical Trial of Cryoimmunotherapy Against Prostate Cancer

A Phase I Clinical Trial of Combined Cryotherapy and Intra-tumoral Immunotherapy With Autologous Immature Dendritic Cells in Men With Castration Resistant Prostatic Cancer and Metastases to Lymph Nodes and/or Bone Pre or Post Chemotherapy

Abstract published at Annual Meeting AACR 2018 in Chicago:

http://www.aacr.org/Meetings/Pages/MeetingDetail.aspx?EventItemID=136#.WzNomaczZaS

Abstract (Online) published Annual Meeting ASCO 2018 in Chicago:

http://abstracts.asco.org/214/AbstView_214_219341.html

Maximum dose dendritic cells administered was well tolerated by interim analysis of 13 patients with database lock September 15th 2017

200 mg pembrolizumab i.v. post-CryoIT was well tolerated - effect is under evaluation.

Haukeland University Hospital

Norwegian Radium Hospital

Alden Cancer Therapy II

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Phase I Clinical Trial of Cryoimmunotherapy Against Prostate Cancer	NCT02423928	Prostate Cancer	Dendritic cell ... Cyclophosphamid... ipilimumab	18 Years -	Alden Cancer Therapy II
Phase I Clinical Trial of Cryoimmunotherapy Against Prostate Cancer	NCT02423928	Prostate Cancer	Dendritic cell ... Cyclophosphamid... ipilimumab	18 Years -	Alden Cancer Therapy II

Spots Global Cancer Trial Database for dendritic cell based cryoimmunotherapy