Targeted Stem Cells Expressing TRAIL as a Therapy for Lung Cancer

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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