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

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ClinicalTrials.gov Identifier: NCT03371485
Recruitment Status : Recruiting
First Posted : December 13, 2017
Last Update Posted : October 1, 2019
Sponsor:
Information provided by (Responsible Party):
Cancer Research UK

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer in the Advanced and Adjuvant Settings Biological: AST-VAC2 Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 1, 2018
Estimated Primary Completion Date : October 16, 2022
Estimated Study Completion Date : October 16, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Active Comparator: Arm A
Patients with advanced NSCLC, to receive AST-VAC2.
Biological: AST-VAC2

Patients will receive up to a maximum of six vaccinations over six weeks. Each weekly AST-VAC2 vaccination will be administered as a split dose via two intradermal injections at a target dose defined as 1 × 107 viable cells. There is no dose escalation planned during this study; only one dose level will be explored.

Each vial of AST-VAC2 will contain 0.6 mL. For each vaccination, vial contents should be drawn into one needle from the vial and delivered as two separate intradermal injections. Each injection will be a maximum of 0.3 mL each. The injections should be administered to the same body site approximately 1 cm apart.

Patients should receive the intradermal injections in either the deltoid muscle on the arm, the outer thigh surface, anterior abdominal wall or buttock.

Six vaccinations will be scheduled however may stop earlier if unacceptable toxicity develops.


No Intervention: Arm B
Patients with advanced NSCLC, receiving no AST-VAC2 treatment and serving as a control for Arm A.
Active Comparator: Arm C:
Patients with previously treated NSCLC, currently disease free, to receive AST-VAC2 in the adjuvant setting.
Biological: AST-VAC2

Patients will receive up to a maximum of six vaccinations over six weeks. Each weekly AST-VAC2 vaccination will be administered as a split dose via two intradermal injections at a target dose defined as 1 × 107 viable cells. There is no dose escalation planned during this study; only one dose level will be explored.

Each vial of AST-VAC2 will contain 0.6 mL. For each vaccination, vial contents should be drawn into one needle from the vial and delivered as two separate intradermal injections. Each injection will be a maximum of 0.3 mL each. The injections should be administered to the same body site approximately 1 cm apart.

Patients should receive the intradermal injections in either the deltoid muscle on the arm, the outer thigh surface, anterior abdominal wall or buttock.

Six vaccinations will be scheduled however may stop earlier if unacceptable toxicity develops.


No Intervention: Arm D:
Patients with previously treated NSCLC, currently disease free, receiving no AST-VAC2 treatment and serving as a control for Arm C.



Primary Outcome Measures :
  1. 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. ]
    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 :
  1. 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. ]
    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.

  2. 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. ]
  3. 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. ]
  4. 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. ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

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): NCT03371485


Contacts
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Contact: John Anderson, Prof 020 7905 2265 j.anderson@ucl.ac.uk

Locations
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United Kingdom
Birmingham University Hospital Recruiting
Birmingham, United Kingdom
Contact: Gary Middleton, Prof         
Southampton General Hospital Recruiting
Southampton, United Kingdom
Contact: Christian Ottensmeier, Prof         
Sponsors and Collaborators
Cancer Research UK

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Responsible Party: Cancer Research UK
ClinicalTrials.gov Identifier: NCT03371485     History of Changes
Other Study ID Numbers: CRUKD/17/003
First Posted: December 13, 2017    Key Record Dates
Last Update Posted: October 1, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cancer Research UK:
Non-small cell lung cancer
Immunotherapy
Cancer vaccine
Dendritic cell vaccine
Allogeneic vaccine
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Vaccines
Immunologic Factors
Physiological Effects of Drugs