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).
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
Drug | Synonyms | Arms |
---|
AST-VAC2 | | Arm 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
Name | Type | Description | Interventions |
---|
Arm A | Active Comparator | Patients with advanced NSCLC, to receive AST-VAC2. | |
Arm B | No Intervention | Patients with advanced NSCLC, receiving no AST-VAC2 treatment and serving as a control for Arm A. | |
Arm C: | Active Comparator | Patients with previously treated NSCLC, currently disease free, to receive AST-VAC2 in the adjuvant setting. | |
Arm D: | No Intervention | Patients 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
November 12, 2020