Phase I Clinical Trial of Cryoimmunotherapy Against Prostate Cancer (CryoIT)
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|ClinicalTrials.gov Identifier: NCT02423928|
Recruitment Status : Completed
First Posted : April 22, 2015
Last Update Posted : October 25, 2019
|Condition or disease||Intervention/treatment||Phase|
|Prostate Cancer||Biological: Dendritic cell based cryoimmunotherapy Drug: Cyclophosphamide Drug: ipilimumab||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||May 2015|
|Actual Primary Completion Date :||August 16, 2019|
|Actual Study Completion Date :||August 16, 2019|
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.
Biological: Dendritic cell based cryoimmunotherapy
Autologous dendritic cells will be obtained following leukapheresis and cytokine induction and will be injected into cryoablated prostate cancer tissue under ultrasound guidance.
Other Name: ACT2001
Low-dose cyclophosphamide will be given metronomically for the purpose of selective inhibition of T regulatory cells for 6 months following start of treatment.
Other Name: Sendoxan
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.
Other Name: Yervoy
- Composite measure of the safety and toxicity profile, including definition of the Maximum Tolerated Dose. [ Time Frame: 72 weeks ]Maximum dose dendritic cells administered was well tolerated by interim analysis of 13 patients with database lock September 15th 2017
- Pembrolizumab tested to boost dendritic cell-based immunity of patients 16 to 18 (3 last recruited patients to the trial). [ Time Frame: 52 weeks ]200 mg pembrolizumab i.v. post-CryoIT was well tolerated - effect is under evaluation.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02423928
|Haukeland University Hospital Research Department|
|Bergen, Hordaland, Norway, No-5021|
|Principal Investigator:||Christian Beisland, MD PhD||Bergen Health|