Targeted Stem Cells Expressing TRAIL as a Therapy for Lung Cancer

• Status: Recruiting
• Trial end date: 2025-09-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University College, London
• Treatments: Cisplatin; Pemetrexed

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