Brief Title
Targeted Stem Cells Expressing TRAIL as a Therapy for Lung Cancer
Official Title
Targeted Stem Cells Expressing TRAIL as a Therapy for Lung Cancer
Brief Summary
The aim of the study is to evaluate the safety and anti-tumour activity of MSCTRAIL in
addition to chemotherapy in metastatic Non-small cell lung cancer (NSCLC) patients in a Phase
I/II clinical trial.
In the phase I study, patients will receive cisplatin and pemetrexed on day one followed by
MSCTRAIL cells on day 2. This constitutes one cycle of treatment. Each patient will receive 3
cycles of treatment at 21 day intervals. The aim of phase 1 is to estimate the recommended
Phase II dose (RP2D) of MSCTRAIL in combination with pemetrexed/cisplatin chemotherapy.
During the phase II study patients will be randomised to either the intervention or the
control arm of the study. All patients in both arms will receive cisplatin and pemetrexed on
day one of treatment. Patients randomised to the intervention arm will receive the
recommended dose of MSCTRAIL from Phase I on day 2 whilst those in the control arm will
receive a placebo. As this is a double blind trial both patients and the clinical team will
not know whether they are receiving MSCTRAIL or a placebo product. The aim of phase 2 is to
assess tolerability and preliminary efficacy of MSCTRAIL in combination with
pemetrexed/cisplatin chemotherapy.
Detailed Description
Phase 1:
A first-in-human, single-centre, accelerated, dose de-escalation design with a modified
Bayesian continual reassessment method (mCRM) to estimate the recommended Phase II dose
(RP2D) of MSCTRAIL in combination with pemetrexed/cisplatin chemotherapy.
The first cohort of three patients will receive cisplatin 75mg/m2 and pemetrexed 500mg/m2 on
day 1 followed by the highest dose of MSCTRAIL, 4x10^8 cells, on day 2. This schedule will be
repeated every 21 days until 3 cycles of treatment have been delivered. It is expected that
patients will receive 4-6 cycles of cisplatin/pemetrexed in total and may continue with
maintenance pemetrexed thereafter.
If there are no DLTs within the first cohort then a subsequent expansion cohort will receive
the same regimen of cisplatin/pemetrexed and MSCTRAIL and data from this expansion cohort
will be used to determine the recommended phase 2 dose (RP2D). Between 6 and 12 patients will
be enrolled into phase I of the trial depending on the number of cohorts assessed.
Phase 2:
A multicentre, randomised, placebo controlled trial comparing MSCTRAIL at the RP2D and
pemetrexed/cisplatin chemotherapy versus pemetrexed/cisplatin chemotherapy alone.
Patients will be randomised 1:1 between the intervention and control arm. Patients entering
the intervention arm will receive cisplatin 75mg/m2 and pemetrexed 500mg/m2 on day 1 followed
by MSCTRAIL at the RP2D on day 2. This schedule will be repeated after 21 days for 3 cycles.
Patients in the control arm with receive cisplatin 75mg/m2 and pemetrexed 500mg/m2 on day 1
and placebo on day 2. This will be repeated after 21 days for up to 3 cycles.
At this point patients will receive a further 1-3 cycles of pemetrexed/ cisplatin alone. They
may then be eligible for maintenance pemetrexed according to clinical response as directed by
their Oncologist in line with local standard of care.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Determination of recommended Phase II dose (RP2D) of MSCTRAIL in combination of cisplatin and pemetrexed treatment (Phase 1)
Secondary Outcome
Frequency of adverse events (Phase 1 & 2)
Condition
Adenocarcinoma of Lung
Intervention
MSCTRAIL
Study Arms / Comparison Groups
Phase 1 - RP2D finding study
Description: Phase I of the trial aims to establish the recommended MSCTRAIL dose when given in combination with cisplatin/pemetrexed chemotherapy in metastatic non-small cell lung cancer (NSCLC) patients
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Genetic
Estimated Enrollment
46
Start Date
March 5, 2019
Completion Date
September 1, 2025
Primary Completion Date
September 1, 2023
Eligibility Criteria
1. Inoperable stage IIIb/IV histologically/cytologically confirmed lung adenocarcinoma
2. EGFR mutation and EML4-ALK translocation negative
3. Patients with evaluable but unmeasurable disease can be included in the phase I study,
but disease must be measurable (CT scan must be within 28 days of randomisation) to be
included in the phase II study
4. ECOG performance status of 0 or 1
5. Life expectancy of at least 12 weeks
6. Age at least 18 years
7. Adequate haematological status:
1. Haemoglobin ≥100g/L
2. Neutrophil count ≥1.5 x 109/L
3. Platelets ≥100 x 109 /L
8. Adequate organ function:
1. Bilirubin ≤1.5 x ULN
2. ALT or AST ≤3 x ULN (≤5 x ULN is acceptable with liver metastases)
3. Creatinine clearance ≥ 60 ml/min (C&G or EDTA)
9. Negative pregnancy test for female patients of child bearing potential.
10. Male subjects and women of child bearing potential must agree to use an acceptable
method of birth control for the duration of the trial and for 12 months after the last
trial treatment administration.
11. Ability to understand and provide written informed consent
12. Ability to comply with the requirements of the protocol
Exclusion Criteria:
1. Prior chemotherapy, hormonal therapy, radiotherapy (including palliative
radiotherapy), immunotherapy or treatment with an investigational drug for advanced
NSCLC.
2. Any surgical procedure in the previous 6 weeks prior to registration/ randomisation
3. Known respiratory failure with baseline resting SpO2 <88%
4. Long term oxygen therapy
5. Severe intercurrent infection
6. Active or infected wounds
7. Yellow fever vaccination within 30 days prior to trial registration/randomisation
8. Subject has known sensitivity to any of the trial drugs to be administered during the
trial.
9. Any contraindication to the administration and use of cisplatin, pemetrexed, vitamin
B12 or folic acid
10. Prior malignancy other than NSCLC (except if the tumour was a non-melanoma skin tumour
that has been completely excised or in situ cervix carcinoma), unless have been
treated with curative intent with no evidence of disease for > 3 years
11. Evidence of symptomatic brain metastases requiring treatment
12. Myocardial infarction, or unstable or uncontrolled disease or condition related to or
impacting cardiac function (e.g., unstable angina, congestive heart failure [New York
Heart Association > class II]) within 1 year of enrolment
13. Known inflammatory bowel disease
14. Known hepatitis B or C infection, human immunodeficiency virus (HIV)-positive patients
15. Pregnant women or those who are breast feeding
16. Other medications, severe acute/chronic medical or psychiatric condition, or
laboratory abnormality that may increase the risk associated with trial participation
or trial drug administration, or may interfere with the interpretation of trial
results, and in the judgment of the investigator would make the patient inappropriate
for entry into this trial
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Sam Janes, +44 207 679 9964, [email protected]
Location Countries
United Kingdom
Location Countries
United Kingdom
Administrative Informations
NCT ID
NCT03298763
Organization ID
UCL/14/0453
Responsible Party
Sponsor
Study Sponsor
University College, London
Study Sponsor
Sam Janes, Principal Investigator, UCL
Verification Date
March 2020