Phase I Clinical Trial of Cryoimmunotherapy Against Prostate Cancer

NCT02423928 | Completed Phase 1 DMC

• 2 other identifiers: ACT20012014-001898-14
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Prostate Cancer

Keywords

immunotherapy; cryoablation; prostate cancer; dendritic cell

Outcome Measures

Primary Outcomes (2)

• Composite measure of the safety and toxicity profile, including definition of the Maximum Tolerated Dose.

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

  72 weeks

• Pembrolizumab tested to boost dendritic cell-based immunity of patients 16 to 18 (3 last recruited patients to the trial).

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

  52 weeks

Study Arms (1)

Cryoimmunotherapy

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: ipilimumab

Interventions

Dendritic cell based cryoimmunotherapy BIOLOGICAL

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

Also known as: ACT2001

Cryoimmunotherapy

Cyclophosphamide DRUG

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

Also known as: Sendoxan

Cryoimmunotherapy

ipilimumab DRUG

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.

Also known as: Yervoy

Cryoimmunotherapy

Eligibility Criteria

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

You may qualify if:

• CRPC (castration resistant prostate cancer) with imaging study proven metastasis beyond pelvic lymph nodes and chemotherapy finished more than three months earlier
• Must be ambulatory with an ECOG performance status of 0 or 1
• No contraindications for MRI (pacemaker, claustrophobia, metal splints)
• Must be able to undergo the surgical procedure under general or regional anesthesia (spinal or epidural)
• Must be at least 18 years of age
• Must have lab values as the following :
• White Blood Cells ≥ 1.5 x 10\^9/L Platelets ≥ 100 x 10\^9/L Hemoglobin ≥ 9g/dL (≥ 5.6 mmol/L) Creatinine ≤ 140 umol/L Bilirubin \< 20% above the upper limit of normal ASAT and ALAT ≤ 2.5 the upper limit of normal Albumin ≥ 2.5 g/L sPSA \< 200 ng/mL
• Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to ICH/GCP, and national/local regulations

You may not qualify if:

• History of other prior malignancy, with the exception of curatively treated basal cell or squamous cell carcinoma of the skin or effectively treated malignancy that has been in remission for over 5 years and is highly likely to have been cured
• Treatment with any other investigational medicinal product (IMP) within 4 weeks prior to first administration of study drug
• Adverse reactions to vaccines such as anaphylaxis or other serious reactions
• History of immunodeficiency or autoimmune disease such as rheumatoid arthritis, systemic lupus erythematosus, sclerodermia, polymyositis-dermatomyositis, juvenile onset insulin-dependent diabetes, or a vasculitic syndrome
• Significant cardiac or other medical illness that would limit activity or survival, such as severe congestive heart failure, unstable angina, or serious cardiac arrhythmia
• Active infection requiring antibiotic therapy
• Known hypersensitivity to any of the components of the cell therapy product
• Patients who test positive for hepatitis B, hepatitis C or HIV (Human Immunodeficiency Virus)
• Use of not permitted concomitant medication: chronic corticosteroids except for asthma inhalers / topical use any agent with a known effect on the immune system, unless it is being given at dose levels that are not immunesuppressive, e.g. prednisone at 10mg/day or less
• Any alternative and complementary drugs that may affect the immune system or be potentially harmful to patients participating in phase I studies
• Any reason why, in the opinion of the investigator, the patient should not participate

Sponsors & Collaborators

• Alden Cancer Therapy II: lead
• Haukeland University Hospital: collaborator
• Norwegian Radium Hospital: collaborator

Study Sites (1)

Haukeland University Hospital Research Department

Bergen, Hordaland, No-5021, Norway

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Cyclophosphamide; Ipilimumab

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Christian Beisland, MD PhD

  Bergen Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2015
• First Posted: April 22, 2015
• Study Start: May 1, 2015
• Primary Completion: August 16, 2019
• Study Completion: August 16, 2019
• Last Updated: October 25, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will share
• Access Criteria: The clinical trial has recruited all 18 patients by January 2019 in order to complete the Phase I clinical trial and with planned database lock and evaluation from August 2019. The interim analyses with database lock September 2017 concludes with good safety data and with therapeutic effects based upon analyses of radiology (stabilized disease of 5 of 13 patients), circulating tumor cells and ultradeep TCR-seq of CDR3 beta-chain of PBMC lymphocytes.

Locations

NO (1)