Targeted Stem Cells Expressing TRAIL as a Therapy for Lung Cancer

NCT ID: NCT03298763

Last Updated: 2021-04-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

46 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-03-05

Study Completion Date

2025-09-01

Brief Summary

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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

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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.

Conditions

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Adenocarcinoma of Lung

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Phase I:

Single centre, accelerated dose 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.

Phase II:

Multicentre, randomised double blind placebo controlled trial comparing MSCTRAIL at the RP2D and pemetrexed/cisplatin chemotherapy versus pemetrexed/cisplatin chemotherapy alone.
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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Phase 1 - RP2D finding study

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

Group Type EXPERIMENTAL

MSCTRAIL

Intervention Type GENETIC

3 doses of MSCTRAIL, administered as an intravenous 60 minutes infusion over 3 cycles, in combination with standard chemotherapy (Cisplatin/Pemetrexed).

After 3 cycles patients will have 1-3 further treatment of pemetrexed and cisplatin without MSCTRAIL.

Phase 2 Intervention Arm

Cisplatin 75mg/m2 and Pemetrexed 500mg/m2 on day 1 followed by MSCTRAIL (at the recommended phase 2 dose) on day 2. This schedule will be repeated after 21 days for 3 cycles.

Patients will then 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.

Group Type ACTIVE_COMPARATOR

MSCTRAIL

Intervention Type GENETIC

3 doses of MSCTRAIL, administered as an intravenous 60 minutes infusion over 3 cycles, in combination with standard chemotherapy (Cisplatin/Pemetrexed).

After 3 cycles patients will have 1-3 further treatment of pemetrexed and cisplatin without MSCTRAIL.

Phase 2 Control Arm

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.

Patients will then 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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo will be made up of the same material used to cryopreserve the ATIMP (MSCTRAIL) but will not include the active product

Interventions

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MSCTRAIL

3 doses of MSCTRAIL, administered as an intravenous 60 minutes infusion over 3 cycles, in combination with standard chemotherapy (Cisplatin/Pemetrexed).

After 3 cycles patients will have 1-3 further treatment of pemetrexed and cisplatin without MSCTRAIL.

Intervention Type GENETIC

Placebo

Placebo will be made up of the same material used to cryopreserve the ATIMP (MSCTRAIL) but will not include the active product

Intervention Type DRUG

Other Intervention Names

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Mesenchymal stromal cells genetically modified to express TRAIL

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University College, London

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sam Janes

Role: PRINCIPAL_INVESTIGATOR

UCL

Locations

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University College London Hospital

London, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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TACTICAL Trial Coordinator

Role: CONTACT

+44 207 679 9964

Bilyana Popova

Role: CONTACT

+44 207 7679 9379

Other Identifiers

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UCL/14/0453

Identifier Type: -

Identifier Source: org_study_id

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