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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02369198




Registration number
NCT02369198
Ethics application status
Date submitted
5/01/2015
Date registered
23/02/2015
Date last updated
7/04/2017

Titles & IDs
Public title
MesomiR 1: A Phase I Study of TargomiRs as 2nd or 3rd Line Treatment for Patients With Recurrent MPM and NSCLC
Scientific title
MesomiR 1: A Phase I Study of Intravenously Administered Epidermal Growth Factor Receptor -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 Std Therapy
Secondary ID [1] 0 0
HREC/13/CRGH/199
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignant Pleural Mesothelioma 0 0
Non-Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - TargomiRs

Experimental: Single arm, open label TargomiRs - 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: as for dose level #3 with a dexamethasone challenge
All patients begin on a micro dose of one billion and increase their dose over 2 weeks and reach their phase 1 dose level on week 3.
Schedule of assessments includes laboratory and physical assessments in the 24 hours after each treatment as well as periodic assessments such as PET and CT scans for tumour assessment.
100% of the data will be source data verified. Analysis will be simple phase 1 analysis based on a 3+3 model.


Treatment: Drugs: TargomiRs
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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
There is a composite primary outcome to establish maximum tolerated dose and dose limiting toxicities The MTD will be determined by the assessment of dose limiting toxicities. - There is a composite primary outcome to establish maximum tolerated dose and dose limiting toxicities.
The MTD will be determined by the assessment of dose limiting toxicities. Toxicities, in the first 2 weeks of treatment for any given patient, are assessed with physical assessments 5 times in the 24 hours starting with a pre-dose assessment, and with laboratory assessments which are assessed 3 times in the 24 hours starting with pre-dose assessment.
All adverse events are graded according to the CTCAE v4.0.
Timepoint [1] 0 0
DLTs assessed from treatment 1 for 2 weeks. MTD is measured from first treatment to toxicity (up to 18 months).
Primary outcome [2] 0 0
to evaluate the effect of multiple dosing of TargomiRs - to evaluate the effect of multiple dosing of TargomiRs using physical and lab assessments as well as tumour response via PET/CT.
Timepoint [2] 0 0
the lab and physical assessments are conducted from first treatment, multiple times in a 24 hour period after treatment for up to 18 months
Primary outcome [3] 0 0
to detect early signs of efficacy - to detect early signs of efficacy using QoL questionnaires and tumour response via PET/CT.
Timepoint [3] 0 0
8 weeks, when formal assessment with RECIST is applied and QoL questionnaires assessed.
Secondary outcome [1] 0 0
QOL assessment - QOL assessment using EORTC QLQ-C30 (Version 3)
Timepoint [1] 0 0
Baseline & weekly or twice weekly (depending on patient's cohort) up to 8 weeks
Secondary outcome [2] 0 0
ECOG PS change - to monitor changes in ECOG PS during treatment
Timepoint [2] 0 0
ECOG PS will be assessed from baseline til 8 weeks
Secondary outcome [3] 0 0
Pulmonary function change - to monitor pulmonary function parameters during treatment using FEV1 and Vital Capacity measurements.
Timepoint [3] 0 0
Pulmonary function is measured in screening and at 8 weeks

Eligibility
Key inclusion criteria
Histological or cytological documentation of MPM or NSCLC and evidence of EGFR expression
in tumour tissue.

Progression during or following the administration of standard 1st, 2nd or 3rd line therapy
regimens.

Patient must have at least one measurable lesion according to the RECIST criteria version
1.1 for NSCLC and modified RECIST criteria for MPM

Male or female patients at least 18 years of age. Eastern Cooperative Oncology Group (ECOG)
performance status of 0 or 1.

Life expectancy of at least 3 months.

Women of childbearing potential and men must agree to use adequate contraception from the
time of signing of the informed consent form until at least 3 months after the last study
drug administration.

Total bilirubin < 1.5 x the upper limit of normal (ULN) ALT and AST < 2.5 x ULN Amylase <
1.5 x ULN Serum creatinine < 1.5 x ULN GFR > 60 ml/min/m2 INR/PTT < 1.5 x ULN (patients who
are therapeutically treated with an agent such as warfarin or heparin will be allowed to
participate provided that no prior evidence of underlying abnormality in coagulation
parameters exists. Close monitoring with at least weekly evaluations will be performed
until INR/APTT is stable (prior to administering the first dose)).

Platelet count > 100.000 and < 800.000, Hemoglobin (Hb) > 9 g/dl, Absolute Neutrophil count
(ANC) > 1500/mm3. Alkaline phosphatase limit < 2.5 x ULN.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Previous phase I drug treatment for the current diagnosis. Previous or concurrent cancer
that is distinct in primary site or histology from MPM or NSCLC within 10 years from the
date of screening EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin
cancer and superficial bladder tumours (Ta, Tis and T1).

Presence of Salmonella antibodies. Herbal supplements (such as St John's Wort), nutritional
supplements and also (multi)-vitamins taken within the last 30 days prior to dosing on Day
1 (and continued use, if appropriate), must be reviewed and approved by the local
investigator.

Major surgical procedures in the last four weeks. Pregnancy or breast-feeding. Congestive
heart failure > New York Heart Association (NYHA) class 2. Unstable angina (angina at rest)
or new-onset angina (< 3 months). Myocardial infarction less than 6 months before
eligibility screening.

Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are
permitted).

Uncontrolled hypertension (Systolic blood pressure > 150 mmHg or diastolic pressure > 90 mm
Hg despite optimal medical management).

Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including
Transient Ischemic Attacks), deep vein thrombosis or pulmonary embolism within 6 months
before the screening radiographic studies.

Ongoing infection > grade 2 NCI-CTCAE version 4.0 HIV infection. Chronic hepatitis B or C.
Patients with a seizure disorder requiring medication. Symptomatic brain metastasis(es).
The patient must not be undergoing acute steroid therapy or steroid tapering (Chronic
steroid therapy is acceptable provided that the dose is stable for one month prior to and
following screening radiographic studies).

Patients with a history of bleeding diathesis: Any hemorrhage or bleeding event of CTCAE
Grade 3 within 4 weeks of the proposed start of study medication.

Renal failure requiring hemo-or peritoneal dialysis. Substance abuse, medical,
psychological or social conditions that in the opinion of the investigator may interfere
with the patient's participation in the study or evaluation of the study results.

Known hypersensitivity to bacterial proteins. Any medical condition that is unstable or
could jeopardize the safety of the patient and his/her compliance in the study.

Unresolved toxicity higher than NCI-CTCAE (version 4.0) Grade 2 attributed to any prior
therapy/procedure excluding alopecia.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital - Sydney
Recruitment hospital [2] 0 0
Chris O'Brien Lifehouse - Sydney
Recruitment hospital [3] 0 0
Northern Cancer Institute - Sydney
Recruitment postcode(s) [1] 0 0
2039 - Sydney
Recruitment postcode(s) [2] 0 0
2050 - Sydney
Recruitment postcode(s) [3] 0 0
2065 - Sydney

Funding & Sponsors
Primary sponsor type
Other
Name
Asbestos Diseases Research Foundation
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
EnGeneIC Limited
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
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
Trial website
https://clinicaltrials.gov/show/NCT02369198
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Nico vanZandwijk, PhD
Address 0 0
University of Sydney
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications