Clinical Trials /

AST-VAC2 Vaccine in Patients With Non-small Cell Lung Cancer

NCT03371485

Description:

This clinical study is looking at a vaccine called AST-VAC2 in adult patients with non-small cell lung cancer (NSCLC) in the advanced and adjuvant settings. The main aim of the study: If the dose can be given safely to patients, learn more about the potential side effects of the vaccine and how they can be managed and also what happens to AST-VAC2 inside the body (looking for effects in the blood, skin or tumour).

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: AST-VAC2 Vaccine in Patients With Non-small Cell Lung Cancer
  • Official Title: A Cancer Research UK Phase I Trial of AST-VAC2 (Allogeneic Dendritic Cell Vaccine) Administered Weekly Via Intradermal Injection in Patients With Non-small Cell Lung Cancer (NSCLC) in the Advanced and Adjuvant Settings

Clinical Trial IDs

  • ORG STUDY ID: CRUKD/17/003
  • NCT ID: NCT03371485

Conditions

  • Non-small Cell Lung Cancer in the Advanced and Adjuvant Settings

Interventions

DrugSynonymsArms
AST-VAC2Arm A

Purpose

This clinical study is looking at a vaccine called AST-VAC2 in adult patients with non-small cell lung cancer (NSCLC) in the advanced and adjuvant settings. The main aim of the study: If the dose can be given safely to patients, learn more about the potential side effects of the vaccine and how they can be managed and also what happens to AST-VAC2 inside the body (looking for effects in the blood, skin or tumour).

Detailed Description

      This clinical study is looking at a vaccine called AST-VAC2. AST-VAC2 has been designed to
      potentially help the immune system attack the cancer. This is a new vaccine which looks
      promising in laboratory studies but it has never been tested in man.

      Dendritic cells occur naturally in your body as part of the immune system however these
      dendritic cells have a special role in finding proteins in the body which are associated with
      cancer and it is hoped that the vaccine will train the immune system to recognise these
      proteins and attack the cancer.

      Some cancers tend to have more of a certain type of protein (part of the body's building
      blocks that make up cells) called 'hTERT' and it has been shown in laboratory studies (and
      also studies in patients using a similar type of vaccine), that targeting hTERT can lead to
      destruction of cancer cells by the immune system. AST-VAC2 will target the hTERT protein.

      Human Leukocyte Antigen (HLA) is another type of protein. An HLA pre-screening test will be
      able to show if a person is positive or negative for a specific HLA protein (AST-VAC2 can
      only work with some types of HLA), as being positive for the protein may mean there is a
      better chance of the vaccine attacking the cancer. Patients who are positive for the specific
      HLA type will be asked to consent to the vaccine arm i.e. to receive the study vaccine. Those
      patients who are negative for the HLA type will be asked to consent to a control arm and will
      not receive the study vaccine.

      The study is in two parts, Part 1 (safety cohort) is to ensure that the vaccine can be given
      safely and to see if there are any initial signs of how it works in the body by performing
      tests on blood and tissue samples. Patients with advanced NSCLC will be asked to participate
      in Part 1.

      Part 2 (expansion cohort) is to continue looking at the safety of the vaccine but also how
      the vaccine works in a group of patients at a different stage of disease. Patients in the
      adjuvant setting will be asked to participate in Part 2.

      Control groups will be recruited for both Parts 1 and 2 of the study.
    

Trial Arms

NameTypeDescriptionInterventions
Arm AActive ComparatorPatients with advanced NSCLC, to receive AST-VAC2.
    Arm BNo InterventionPatients with advanced NSCLC, receiving no AST-VAC2 treatment and serving as a control for Arm A.
      Arm C:Active ComparatorPatients with previously treated NSCLC, currently disease free, to receive AST-VAC2 in the adjuvant setting.
        Arm D:No InterventionPatients with previously treated NSCLC, currently disease free, receiving no AST-VAC2 treatment and serving as a control for Arm C.

          Eligibility Criteria

                  Inclusion Criteria:
          
                    1. a) Safety cohort (Arms A & B): Patients with advanced NSCLC (metastatic or locally
                       advanced), for whom there are no other suitable treatment options.-
          
                         -  Able to and likely to be well enough to receive six vaccinations i.e. judged by
                            the Investigator to not require alternate treatment for the duration of the
                            vaccination schedule and period to off trial visit.
          
                         -  Has had sufficient wash out periods from previous treatments as follows:
          
                            i) four weeks for chemotherapy ii) six weeks for investigational medicinal
                            products (IMPs) iii) eight weeks for immunotherapy (shorter intervals may be
                            acceptable based on half-life of treatment. Eligibility will be confirmed by the
                            Sponsor and CI).
          
                         -  Measurable disease
          
                         -  Biopsiable disease is preferable however patients without biopsiable disease can
                            still be considered for the study.
          
                            b) Expansion cohort (Arms C & D): NSCLC patients in the adjuvant setting,
                            currently disease free, who have completed all suitable treatment options
                            (chemotherapy +/- surgery).-
          
                         -  Able to and likely to be well enough to receive six vaccinations i.e. judged by
                            the Investigator to not require alternate treatment for the duration of the
                            vaccination schedule and period to off trial visit.
          
                    2. Written (signed and dated) informed consent and be capable of co-operating with
                       treatment and follow-up.
          
                    3. Confirmed HLA A*02:01 positive genotype (Treatment arms A and C only).
          
                    4. Life expectancy of at least 12 weeks.
          
                    5. World Health Organisation (WHO) performance status of 0-2.
          
                    6. Haematological and biochemical indices within the ranges shown below. These
                       measurements must be performed prior to the patient receiving the first AST-VAC2
                       vaccination.
          
                       Laboratory Test and Value required
          
                       Haemoglobin (Hb) ≥9.0 g/dL Absolute neutrophil count (ANC) ≥1.5 x 10^9 /L Platelet
                       count ≥100 x 10 ^9/L Lymphocyte count >1.0 x 10^9 /L Bilirubin ≤1.5 x upper limit of
                       normal (ULN) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) and
                       alkaline phosphatase (ALP) ≤ 3.0 x ULN Calculated creatinine clearance > 30 mL/min
          
                    7. 18 years or over at the time consent is given.
          
                  Exclusion Criteria:
          
                    1. Radiotherapy (except for palliative reasons) during the previous four weeks before
                       treatment.
          
                    2. Ongoing toxic manifestations of previous treatments greater than CTCAE Grade 1.
                       Exceptions to this are alopecia or certain Grade 2 toxicities, which in the opinion of
                       the Investigator and the Sponsor should not exclude the patient.
          
                    3. Systemic steroids or other drugs with a likely effect on immune competence are
                       forbidden during the trial. The predictable need of their use will preclude the
                       patient from trial entry.
          
                    4. Female patients who are able to become pregnant (or are already pregnant or
                       lactating). However, those patients who have a negative serum or urine pregnancy test
                       before enrolment and agree to use two forms of contraception (one effective form plus
                       a barrier method) [oral, injected or implanted hormonal contraception and condom;
                       intra-uterine device and condom; diaphragm with spermicidal gel and condom] or agree
                       to sexual abstinence*, effective from the first administration of AST-VAC2 throughout
                       the trial and for six months afterwards are considered eligible. (treatment arms only)
          
                    5. Male patients with partners of child-bearing potential (unless they agree to take
                       measures not to father children by using a barrier method of contraception [condom
                       plus spermicide] or to sexual abstinence* effective from the first administration of
                       AST-VAC2, throughout the trial and for six months afterwards. Men with partners of
                       child-bearing potential must also be willing to ensure that their partner uses an
                       effective method of contraception for the same duration for example, hormonal
                       contraception, intrauterine device, diaphragm with spermicidal gel or sexual
                       abstinence). Men with pregnant or lactating partners must be advised to use barrier
                       method contraception (for example, condom plus spermicidal gel) to prevent exposure of
                       the foetus or neonate (treatment arms only)
          
                    6. Major thoracic or abdominal surgery from which the patient has not yet recovered.
          
                    7. At high medical risk because of non-malignant systemic disease including active
                       uncontrolled infection.
          
                    8. Known to be serologically positive for Hepatitis B, Hepatitis C or Human
                       Immunodeficiency Virus (HIV).
          
                    9. Evidence of any ongoing active autoimmune disease.
          
                   10. Concurrent congestive heart failure, prior history of class III/ IV cardiac disease
                       (New York Heart Association [NYHA]), prior history of cardiac ischaemia or prior
                       history of cardiac arrhythmia.
          
                   11. Is a participant or plans to participate in another interventional clinical trial,
                       whilst taking part in this Phase I trial of AST-VAC2. Participation in an
                       observational trial or interventional clinical trial which does not involve
                       administration of an IMP and which would not place an unacceptable burden on the
                       patient in the opinion of the Investigator and Medical Advisor would be acceptable.
          
                       Control arm patients:
          
                       If a patient in either of the control arms consequently wishes to consent to another
                       treatment trial/withdraw from the trial for other reasons, prior to the end of their
                       follow up period, then their follow up information as per Section 7.4, will be
                       recorded in the electronic case report form (eCRF) and the patient will be withdrawn
                       from the trial.
          
                   12. Any vaccination given within four weeks before the first AST-VAC2 vaccination.
          
                   13. Any planned prophylactic vaccination from trial entry until completion of the AST-VAC2
                       vaccinations.
          
                   14. Any condition which might interfere with the patient's ability to generate an immune
                       response.
          
                   15. Any other condition which in the Investigator's opinion would not make the patient a
                       good candidate for the clinical trial.
          
                         -  Abstinence is only considered to be an acceptable method of contraception when
                            this is in line with the preferred and usual lifestyle of the subject. Periodic
                            abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and
                            withdrawal are not acceptable methods of contraception.
                
          Maximum Eligible Age:N/A
          Minimum Eligible Age:18 Years
          Eligible Gender:All
          Healthy Volunteers:No

          Primary Outcome Measures

          Measure:Treatment emergent adverse events
          Time Frame:Assessed from the time a patient consents to the main study until 30 days after a patient's last vaccination (maximum of 6 weekly vaccines) or until the patient starts another anti-cancer therapy, whichever is sooner.
          Safety Issue:
          Description:This will be done by determining the frequency and causality of each adverse event to AST-VAC2 and grading severity according to the NCI CTCAE Version 4.02 or protocol specific grading system for Injection Site Reactions.

          Secondary Outcome Measures

          Measure:Peripheral immune response
          Time Frame:Screening, vaccination weeks 3, 4 and 6, 2 weeks post last vaccination and 3, 6 and 12 months post a patient's first vaccination.
          Safety Issue:
          Description:This will be done by the Observation of the total number of patients showing durable peripheral immune response, defined as a change in one validated assay at two time points after at least two vaccinations.
          Measure:2-year overall survival for patients receiving the AST-VAC2 vaccine in the safety cohort.
          Time Frame:2 years post a patient's first vaccination.
          Safety Issue:
          Description:
          Measure:2-year overall survival in patients receiving the AST-VAC2 vaccine in the expansion cohort
          Time Frame:2 years post a patient's first vaccination.
          Safety Issue:
          Description:
          Measure:Time to relapse in patients receiving the AST-VAC2 vaccine in the expansion cohort
          Time Frame:Up to 2 years post a patient's first vaccination.
          Safety Issue:
          Description:

          Details

          Phase:Phase 1
          Primary Purpose:Interventional
          Overall Status:Recruiting
          Lead Sponsor:Cancer Research UK

          Trial Keywords

          • Non-small cell lung cancer
          • Immunotherapy
          • Cancer vaccine
          • Dendritic cell vaccine
          • Allogeneic vaccine

          Last Updated