Clinical Trial: NCT03412786 - My Cancer Genome

NCT03412786

Description:

In this Phase I study, patients with hormone-sensitive Prostate Cancer (PC) and lymph node metastases are treated with the cancer vaccine Bcl-xl_42-CAF09b. The aim of the study is to clarify the safety and toxicity of the vaccine and also the immunological effect. The vaccine Bcl-xl_42-CAF09b is composed of the peptide Bcl-xl_42 and the adjuvant CAF09b. The B-cell lymphoma extra large protein (Bcl-xl) protein plays a vital role in the cancer cell's ability to avoid programmed cell death (apoptosis) and is upregulated in a variety of cancerous diseases. Bcl-xl_42 is a peptide fragment of the full protein and preclinical studies have shown that vaccination with this peptide (Bcl-xl) can activate the immune system and thereby lead to the death of cancer cells. In order to improve the activation of the immune system, adjuvant CAF09b is added; Preclinical studies have shown that special intraperitoneal (IP) injections of CAF09b improve the activation of the immune system.

Related Conditions:

Prostate Adenocarcinoma

Recruiting Status:

Recruiting

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT03412786

Trial Eligibility

Document

Title

Brief Title: Bcl-XL_42-CAF09b Vaccination for Patients With Prostate Cancer With Lymph Node Metastases
Official Title: A Phase I Study of the Bcl-XL_42-CAF09b Vaccine to Test Safety and Immunological Effect in Patients With Prostate Cancer With Lymph Node Metastases

Clinical Trial IDs

ORG STUDY ID: UR1534
NCT ID: NCT03412786

Conditions

Prostate Cancer

Interventions

Drug	Synonyms	Arms
Bcl-Xl_42-CAF09b vaccine		Arm A: IM followed by IP

Purpose

Detailed Description

      Background:

      In this Phase I study, patients with hormone-sensitive Prostate Cancer (PC) and lymph node
      metastases are treated with the cancer vaccine Bcl-xl_42-CAF09b. The aim of the study is to
      clarify the safety and toxicity of the vaccine and also the immunological effect.

      Patients included should be on Bicalutamid treatment upon inclusion. The vaccine
      Bcl-xl_42-CAF09b is composed of the peptide Bcl-xl_42 and the adjuvant CAF09b. The B-cell
      lymphoma extra large protein (Bcl-xl) protein plays a vital role in the cancer cell's ability
      to avoid programmed cell death (apoptosis) and is upregulated in a variety of cancerous
      diseases. Bcl-xl_42 is a peptide fragment of the full protein and preclinical studies have
      shown that vaccination with this peptide (Bcl-xl) can activate the immune system and thereby
      lead to the death of cancer cells.

      In order to improve the activation of the immune system, adjuvant CAF09b is added;
      Preclinical studies have shown that special intraperitoneal (IP) injections of CAF09b improve
      the activation of the immune system.

      The CAF09 adjuvant has been developed by Statens Serum Institut (SSI). It is a
      three-component adjuvant system, composed of cationic liposomes (DDA-MMG1) with complex bound
      synthetic double-stranded RNA (Poly(I:C)2). The adjuvant was developed as a means to induce
      cytotoxic CD8+ T-cell responses against vaccine antigens and intended for use in vaccines
      against disease targets such as cancers, human immunodeficiency virus or Hepatitis C virus.
      The Poly(I:C) component has previously been in clinical studies as a cancer treatment.
      Poly(I:C) is known for its pyrogenic activity but upon formulation in the cationic liposome
      system, CAF09, the pyrogenic effect is significantly reduced.

      Methods:

      20 patients will be included in this phase I trial. 10 patients will be included in arm A and
      10 patients in arm B. Arm a will recieve 3 vaccines every second week IM and thereafter 3
      vaccines every second week IP. Arm B will first receive 3 vaccines every second week IP and
      thereafter every second week IM. All 20 patients will recieve 6 vaccines all in all. This is
      not randomized - the first 10 patients included will be in arm A and the last 10 patients
      included will be in arm B.

      Patients will be followed with clinical controls every second week.

Trial Arms

Name	Type	Description	Interventions
Arm A: IM followed by IP	Experimental	Will be administered first 3 vaccines biweekly IM and thereafter 3 vaccines biweekly IP.	Bcl-Xl_42-CAF09b vaccine
Arm B: IP followed by IM	Experimental	Will be administered first 3 vaccines biweekly IP and thereafter 3 vaccines biweekly IM.	Bcl-Xl_42-CAF09b vaccine

Eligibility Criteria

        Inclusion Criteria:

          1. Age ≥ 18 years

          2. Histologically Verified Adenocarcinoma Prostatae

          3. Diagnostic and / or histologically verified lymph node metastases

          4. ECOG Performance Status ≤2

          5. Primary anti-androgen treatment started

          6. Adequate haematological, renal and hepatic function:

               1. Neutrophil granulocytes ≥ 1.5 x 109 / l

               2. Platelet counts ≥ 100 x 109 / l

               3. hemoglobin ≥ 5.6 mmol / l

               4. Serum creatinine ≤ 1.5 times upper normal limit

               5. AST or ALAT ≤ 2.5 times upper normal limit

               6. serum bilirubin ≤ 1.5 times upper normal limit

               7. Alkaline phosphatase ≤ 2.5 times upper normal limit

               8. INR <1.5 / PP <40

        Exclusion Criteria:

          1. Verified bone or visceral metastases

          2. Serious allergy or previous anaphylactic reactions

          3. Known hypersensitivity to any of the active substances or to any of the excipients.

          4. Other malignant disease within the last three years, rendering planocellular and
             basocellular skin carcinoma

          5. Known infection with HIV, hepatitis B and C virus, regardless of whether the infection
             is kept calm with medical treatment

          6. Severe medical disorder, severe asthma, severe COPD, poorly regulated cardiovascular
             disease or diabetes

          7. Active autoimmune disease, e.g. autoimmune neutropenia / thrombocytopenia or hemolytic
             anemia, systemic lupus erythematosus, scleroderma, myasthenia gravis, goodpasture
             syndrome, Addison's disease, Hashimoto's thyroiditis, active grave disease, morbus
             chrohn or ulcerative colitis

          8. Major gastrointestinal surgical procedures within the last 3 months

          9. Previous treatment with other cancer vaccine

         10. Concomitant immunosuppressive treatment including prednisolone and methotrexate

         11. Ongoing anticoagulant treatment (treatment with acetylsalicylic acid and clopidogrel
             is allowed)

         12. Psychiatric disease which, according to the investigator's discretion, may affect
             compliance

         13. Co-administration with other experimental drugs.

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	Male
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Number and type of reported adverse events
Time Frame:	0-30 weeks
Safety Issue:
Description:	Determine the safety of the Bcl-XL_42-CAF09b vaccine for patients with prostate cancer with lymph node involvement who are on Bicalutamid treatment by reporting adverse events according to CTCAE v. 4.0

Secondary Outcome Measures

Measure:	Treatment related immune responses
Time Frame:	Up to 24 months
Safety Issue:
Description:	To evaluate the immunological impact of the treatment in both arm A and arm B. Elispot and tetramer staining methods will be Applied to identify Bcl-XL_42 peptide specific T cells in the blood over time

Details

Phase:	Phase 1
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	Herlev Hospital

Last Updated

August 12, 2020

Clinical Trials /

Bcl-XL_42-CAF09b Vaccination for Patients With Prostate Cancer With Lymph Node Metastases