RecruitingPhase 1ACTRN12614001248651

The first testing of TargomiRs in the human setting: dose-finding studies in patients with recurrent malignant pleural mesothelioma and non-small cell lung cancer

MesomiR 1: A Phase I study of intravenously administered Epidermal Growth Factor Receptor (EGFR)-targeted, EnGeneIC Delivery Vehicle (EDV)-packaged, miR-16 mimic (TargomiRs) for patients with Malignant Pleural Mesothelioma (MPM) and advanced Non-Small Cell Lung Cancer (NSCLC) failing on standard therapy

Sponsor

Asbestos Disease Research Institute

Enrollment

30 participants

Start Date

Sep 29, 2014

Study Type

Interventional

Conditions

Malignant Pleural Mesothelioma

Summary

This study will evaluate the safety and effect of a new treatment known as TargomiRs in patients with malignant pleural mesothelioma (MPM) and non-small cell lung cancer (NSCLC). Who is it for? You may be eligible to join this study if you are aged 18 years or above, and have a confirmed diagnosis of MPM or NSCLC, with evidence of Epidermal growth factor receptor (EGFR) in tumour tissue. Study details: All participants in this study will receive treatment with a new targeted therapy known as TargomiRs. Treatment will be administered by injection into the vein (i.e. intravenously) at a frequency of once or twice weekly until it is clear that you are not benefitting from the treatment. Initially a low dose will be administered to participants. If this dose is tolerated, then it will be increased in the next group of patients and so on until the maximum tolerated dose is determined. All participants will be regularly monitored for safety and toxicity of the treatment for 24 hours after each treatment in the first 2 weeks and 3 hours after treatment from week 3 onwards. They will also be required to complete QoL questionnaires each treatment and have PET scans and lung function tests approximately once every 8 weeks in order to evaluate treatment effect and quality of life. It is hoped that the treatment offered will cause the diseased tissues to respond in a way that will block uncontrolled tumour growth resulting in tumour control and give patients a longer life.

Eligibility

Sex: Both males and femalesMin Age: 18 Yearss

Plain Language Summary

Simplified for easier understanding

This study is the first human test of a new treatment called TargomiRs for patients with mesothelioma (a cancer caused by asbestos) or advanced non-small cell lung cancer (NSCLC) that has returned after previous treatment. TargomiRs are tiny particles that carry anti-cancer genetic material directly to tumour cells. Participants will receive TargomiRs by intravenous infusion at increasing doses, starting low and increasing carefully until the safest and most effective dose is found. You may be eligible if: - You are 18 years or older - You have been diagnosed with malignant pleural mesothelioma (MPM) or non-small cell lung cancer (NSCLC) - Your tumour has a marker called EGFR - Your cancer has progressed after at least one standard treatment - You have at least one measurable tumour site - Your general health is reasonably good (ECOG 0-1) - Your life expectancy is at least 3 months You may NOT be eligible if: - You are pregnant or breastfeeding - You have brain metastases with active symptoms - You have significant heart conditions (recent heart attack, severe heart failure, uncontrolled blood pressure) - You have HIV, active Hepatitis B or C - You have had major surgery in the last 4 weeks Talk to your doctor about whether this trial might be right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

TargomiRs are targeted minicells containing a microRNA mimic. They consist of three components: 1. A miR-16-based microRNA mimic. The miR-16 family has been implicated as a tumour suppressor in a range of cancer types. The mimic is a double-stranded, 23 base pair, synthetic RNA molecule. 2. Drug delivery vehicle – EDVs. EDVs are nonliving bacterial minicells (nanoparticles). They function as leak resistant micro-reservoir carriers that allow efficient packaging of a range of different drugs, proteins or nucleic acids. 3. Targeting moiety. The EDVs are targeted to EGFR-expressing cancer cells with an anti-EGFR bispecific antibody. TargomiRs are IV injected. Phase 1 Planned dose levels Dose level 1: 5 billion once a week Dose level 2: 5 billion twice a week Dose level 3: 5 billion once a week with cardiac monitoring Dose level 4: 2.5 billion twice a week with cardiac monitoring Dose level 5: 2.5 billion twice a week with dexamethasone challenge and cardiac monitoring All patients begin on modified, micro doses to allow the body the opportunity to adjust to the introduction of EDVs into the body. The full phase 1 dose for a patient is reached in treatment week 3. Duration of treatment for each dose level is on a patient by patient basis. Officially the cycle is 8 weeks long however a patient can continue on treatment if they are deriving clinical benefit from the treatment. If at any time point before or after the 8 week mark, a patient progresses, experiences ongoing or unreasonable toxicities or withdraws from the study, they will cease treatment. Escalation of dose in cohorts of 3-6 patients per dose level. If at least 2 patients are observed to experience Dose Limiting Toxicity (DLT), the prior dose level is defined as the MTD. Cardiac monitoring includes a Sestamibi scan and Echo before the patient begins on TargomiR treatment and if any cardiac changes are observed whilst the patient receives treatment, these scans are to be repeated and a Troponin blood level obtained. ECGs are obtained on the same schedule as all previous cohorts. Dexamethasone is one of the pre-medications given prior to TargomiRs. The dexamethasone challenge seeks to reduce the amount of dexamethasone given to patients during the course of their treatment period. The schedule is to reduce the dose from 4mg to nil over the course of 8 weeks so long as the patient does not experience undue allergic actions to the TargomiRs. Adherence to the protocol tends not to be problematic in patient groups where the trial treatment is their only treatment option. They are often very keen to participate and motivated to be part of the research.