Targeted Stem Cells Expressing TRAIL as a Therapy for Lung Cancer

NCT03298763 | Unknown Phase 1 DMC

• 1 other identifier: UCL/14/0453
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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.

Conditions

Adenocarcinoma of Lung

Outcome Measures

Primary Outcomes (2)

• Determination of recommended Phase II dose (RP2D) of MSCTRAIL in combination of cisplatin and pemetrexed treatment (Phase 1)

  The dose recommended for phase II (i.e. the Maximum Tolerated Dose, or MTD) will be the largest dose that has an estimated risk of causing DLT (defined as MSCTRAIL related adverse event of grade 3 or higher) equal or closest to the target level of 35% (the target toxicity level). A modified Bayesian continual reassessment method (mCRM) will be used.

  until 21 days after the last dose of MSCTRAIL

• Tumour response rate (Phase 2)

  At each visit patients will be assigned a RECIST visit response of CR, PR, SD or PD depending on the status of their disease compared to baseline and previous assessments. Objective tumour response rate is defined as the percentage of patients who have a confirmed visit response of CR or PR prior to any evidence of progression (as defined by RECIST 1.1).

  12 weeks post 1st MSCTRAIL infusion

Secondary Outcomes (4)

• Frequency of adverse events (Phase 1 & 2)

  Up to 12 weeks post 1st MSCTRAIL infusion

• Best Overall response (Phase 1&2)

  Until end of follow up period (Phase 1: 1 year post last treatment, Phase 2: 2 years post last treatment)

• Progression free survival (Phase 1 & 2)

  End of follow up period (Phase 1: 1 year post last treatment, Phase 2: 2 years post last treatment)

• Overall survival (Phase 2)

  End of follow up period (2 years post last treatment)

Study Arms (3)

Phase 1 - RP2D finding study

EXPERIMENTAL

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

Genetic: MSCTRAIL

Phase 2 Intervention Arm

ACTIVE COMPARATOR

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.

Genetic: MSCTRAIL

Phase 2 Control Arm

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

MSCTRAIL 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.

Also known as: Mesenchymal stromal cells genetically modified to express TRAIL

Phase 1 - RP2D finding study; Phase 2 Intervention Arm

Placebo DRUG

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

Phase 2 Control Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Prior chemotherapy, hormonal therapy, radiotherapy (including palliative radiotherapy), immunotherapy or treatment with an investigational drug for advanced NSCLC.
• Any surgical procedure in the previous 6 weeks prior to registration/ randomisation
• Known respiratory failure with baseline resting SpO2 \<88%
• Long term oxygen therapy
• Severe intercurrent infection
• Active or infected wounds
• Yellow fever vaccination within 30 days prior to trial registration/randomisation
• Subject has known sensitivity to any of the trial drugs to be administered during the trial.
• Any contraindication to the administration and use of cisplatin, pemetrexed, vitamin B12 or folic acid
• 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
• Evidence of symptomatic brain metastases requiring treatment
• 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
• Known inflammatory bowel disease
• Known hepatitis B or C infection, human immunodeficiency virus (HIV)-positive patients
• Pregnant women or those who are breast feeding

Sponsors & Collaborators

• University College, London: lead

Study Sites (1)

University College London Hospital

London, United Kingdom

RECRUITING

MeSH Terms

Conditions

Adenocarcinoma of Lung

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site

Study Officials

• Sam Janes

  UCL

  PRINCIPAL INVESTIGATOR

Central Study Contacts

TACTICAL Trial Coordinator

CONTACT

+44 207 679 9964; ctc.tactical@ucl.ac.uk

Bilyana Popova

CONTACT

+44 207 7679 9379; b.popova@ucl.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 20, 2017
• First Posted: October 2, 2017
• Study Start: March 5, 2019
• Primary Completion: September 1, 2023
• Study Completion: September 1, 2025
• Last Updated: April 28, 2021

Record last verified: 2021-04

Locations

GB (1)