Clinical Trials Details

Public Title   

Cancer Molecular Screening and Therapeutics (MoST) Program Addendum 17 - substudies 38-39: Tepotinib | MoST Addendum 17

Contacts   

Dr Lucille Sebastian
NHMRC Clinical Trials Centre
Medical Foundation Building
Levels 4-6, 92-94 Parramatta Road
Camperdown NSW 2050
+61 295625000 (phone)
[email protected]
Australia

Recruitment Status   

Active, not recruiting

Trial ID   

ACTRN12621000811808

Focus of Trial   

Treatment: Targeted and biological therapies

Phase of Trial   

Phase 2

Cancer Stage   

Metastatic/Widespread

Recruitment Dates   

Anticipated start date
01/07/2021

Anticipated end date
01/07/2023

Location of Trial   

NSW
NT
QLD
SA
TAS
WA
VIC

Trial Summary   

This is a substudy of the Cancer Molecular Screening and Therapeutics (MoST) Program, which is registered on ANZCTR with ID ACTRN12616000908437. This substudy will evaluate the activity of tepotinib in a population of participants with metastatic non-small cell lung cancers (NSCLC) harbouring METex14 skipping mutations identified using comprehensive genomic profiling (CGP).

Who is it for?
You may be eligible to join the study if you are aged 18 years and older, with pathologically confirmed metastatic NSCLC. Your tumour will need to harbour METex14 skipping mutations identified using CGP.

Study details:
Participants will receive tepotinib treatment. The tepotinib is to be taken orally, at 500mg once daily (days 1 to 21 in a 21-day treatment cycle).
Tepotinib will be given to participants continuously as long as they and their doctor agree there is a benefit from treatment. Participants will undergo imaging assessments at 6 weekly intervals from first treatment until 18 weeks, and then 12 weekly intervals until progression. Safety and tolerability of treatment will be assessed at 3 weekly intervals. Health related quality of life during treatment will be assessed at 3 weekly intervals and then every 9 weeks after end of treatment for 12 months, and then every 12 weeks until progression.

We cannot guarantee that participants will receive any benefits from this study. This study is being carried out to improve the way we treat cancer patients who may have limited treatment options available to them. It is hoped that tepotinib will be well tolerated and will improve outcomes for future patients, however, there may be no clear benefit from participation in this study.

Description of the Study   


Description of the Control
No control group

Description of the Intervention
Participants will receive continuous tepotinib. Tepotinib will be administered as tablets, to be taken orally by participants, at a dose of 500mg daily (days 1 to 21 in a 21-day treatment cycle). Tepotinib is to be taken continuously with no interruption between cycles.

If participants experience any severe (grade 3-4) adverse events, treatment will be withheld until the adverse event is resolved (grade 0-1). If participants experience intolerable toxicity, tepotinib dose may be reduced to 250mg once daily. If a second dose reduction is required, the patient should discontinue study treatment.

Participants will receive tepotinib until disease progression is documented, intolerable toxicity or withdrawal for another reason. Participants will be asked to return unused drug and empty drug containers at each return visit. The Pharmacy Department at participating institutions will maintain a record of drugs dispensed for each participant.

Allocation to Intervention
Non-randomised trial

Target Sample Size   

32

Primary Outcomes   

The primary objective is to assess the clinical activity of tepotinib using objective tumour response rate (OTRR), based on complete or partial response using cancer specific response criteria such as RECIST v1.1, RANO or disease-specific guidelines.
Imaging (eg. CT scans) for disease evaluation will take place every 6 weeks from first dose of study treatment until 18 weeks, then every 12 weeks until disease progression.


Secondary Outcomes   

Overall survival (OS) (death from any cause)

For the duration of the study. From the date of registration to date of death from any cause, or the date of last known follow-up alive.


Progression free survival (PFS). PFS is defined as the interval from date of registration to the date of first evidence of disease progression or death from any cause, whichever occurs first. Participants who did not progress or die will be censored on the date of their last clinical assessment or tumour assessment. Disease progression is defined according to RECIST v1.1, RANO guidelines, or disease specific guidelines.

Imaging (eg. CT scans) for disease evaluation will take place every 6 weeks from first dose of study treatment until 18 weeks, then every 12 weeks until disease progression.


Time to treatment failure. This is defined as the interval from the date of registration to date of permanently ceasing study treatment for any reason. Participants who are still on study treatment at time of analysis will be censored on the date of their last reported study treatment. Patients who receive subsequent systemic cancer therapy before progression will be considered to be censored at the time of commencement of subsequent therapy.

Time to treatment failure analysis is performed at 12 months from last patient registration.


Depth of response, defined as the percentage of tumour shrinkage based on the sum of the longest diameters of all target lesions observed at the lowest point (nadir), compared with the sum of their diameters at baseline.
Imaging (eg. CT scans) for disease evaluation will take place every 6 weeks from first dose of study treatment until 18 weeks, then every 12 weeks until disease progression.

Duration of response according to RECIST 1.1


Imaging (eg. CT scans) for disease evaluation will take place every 6 weeks from first dose of study treatment until 18 weeks, then every 12 weeks until disease progression.

Progression Free Survival (PFS) at 6 months. PFS is defined as the interval from date of registration to the date of first evidence of disease progression or death from any cause, whichever occurs first and is the proportion of participants on study who are alive and progression free at 6 months. The disease progression is defined according to RECIST v1.1, RANO guidelines, or disease specific guidelines.
At 6 months post participant registration via imaging (e.g. CT) scans of disease evaluation


Safety and tolerability of treatment (rates of adverse events). All adverse events (AEs), including event grading as per NCI CTCAE criteria, will be captured from the first dose of study treatment until 30 days after cessation of study treatment. Reported AEs by participants will be documented by study site staff and subsequently transcribed into the study electronic data capture (EDC) system. In order to evaluate the safety and tolerability of the study treatment, the entered AE types, frequency and severity in the EDC will be analysed.
Adverse events will be recorded from the first dose of study treatment until 30 days after cessation of study treatment.


Health related quality of life during treatment assessed using the EORTC QLQ-C30 Form.
Every 3 weeks from first dose of study treatment until end of treatment. Subsequently, every 9 weeks for 12 months and then every 12 weeks until disease progression.

Health related quality of life during treatment assessed using The Brief Pain Inventory Form.
Every 3 weeks from first dose of study treatment until end of treatment. Subsequently, every 9 weeks for 12 months and then every 12 weeks until disease progression.

Side Effects   

Very common (experienced by more than 1 in 10 participants);
- Oedema (excess fluid in body tissue, causing swelling of the hands and feet or face)
- Nausea and/or vomiting
- Changes in bowel habits like diarrhoea or constipation
- Blood creatinine increase (which may indicate possible kidney injury)
- Low albumin level
- Shortness of breath
- Cough
- Reduced appetite
- Tiredness and/or generalised weakness
- Pleural effusion (abnormal fluid collection in the lungs)
- Increase in amylase or lipase (enzymes indicating possible pancreas inflammation)
- Back pain

Common (experienced by between 1 in 10 and 1 in 100 patients):
- Ascites (abnormal fluid collection in the abdomen)
- AST and ALT increase (increase in liver enzyme, indicating possible liver damage)
- Lung infections
- Pulmonary embolism (blood clots in the lung which can cause difficulty breathing, chest pain and/or lightheadedness). Tell your doctor right away if you experience any of these symptoms: chest pain, difficulty breathing, lightheadedness, irregular or rapid heartbeats.
- Abdominal pain
- Fever

Uncommon (experienced by between 1 in 100 and 1 in 1000 participants):
- Rash
- Inflammation of lungs (pneumonitis) or interstitial lung disease (ILD; lung scarring, which can cause difficulty breathing, cough and fever). In tepotinib clinical trials, this potentially serious side effect has been reported. It is very important that you tell the study staff immediately about any side effects.
- Heart rhythm abnormalities such as QT prolongation (a condition that can lead to fast or erratic heartbeats). Tell your doctor right away if you have an abnormal or fast heartbeat or if you feel dizzy, lightheaded, or faint. These may be symptoms related to QT prolongation.

Inclusion Criteria   

1. Adults, aged 18 years and older, with newly diagnosed metastatic non-squamous NSCLC;
2. METex14 skipping mutation identified using CGP;
3. Confirmation of molecular eligibility by the molecular tumour board;
4. Measurable disease as assessed by RECIST 1.1; In the event of evaluable but non-measurable disease, eligibility must be confirmed by the ASPiRATION study chair or delegate through contacting the NHMRC CTC;
5. ECOG 0 to 2;
6. Adequate organ system function as assessed by the following minimal laboratory requirements (within 7 days prior to first administration of study drug):
a. bone marrow function; platelets greater than or equal to 100 x 10^9/L, ANC greater than or equal to 1.5 x 10^9/L, and haemoglobin greater than or equal to 90g/L (5.6mmol/L);
b. liver function; ALT/AST less than or equal to 3xULN (in the absence of liver metastases, less than or equal to 5xULN for patients with liver involvement) and total bilirubin less than or equal to 1.5xULN;
c. renal function; serum creatinine less than or equal to 1.5xULN;
7. Life expectancy greater than or equal to 12 weeks;
8. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments;
9. Signed, written informed consent to participation in the specific treatment substudy.

Minimum Age:
18 Years

Maximum Age:
No limit

Gender:
Both males and females

Cost and Time Commitments   

Similar cost as usual care
More time commitment than usual care
Additional travel commitments

Ethics Approval   

Approved

Trial Sponsors   

Primary Sponsor:
University
The University of Sydney
NHMRC Clinical Trials Centre
Locked Bag 77
Camperdown NSW 1450
Australia

Secondary Sponsor:
None




Other Collaborator:
Other Collaborative groups
Australian Genomic Cancer Medicine Centre (AGCMC)
Kinghorn Cancer Centre,
370 Victoria Street
Darlinghurst NSW 2010
Australia

Funding Source   

Government body
Office for Health and Medical Research
Locked Bag 961
North Sydney NSW 2059
Australia
Other Collaborative groups
Australian Genomic Cancer Medicine Centre (AGCMC)
Kinghorn Cancer Centre,
370 Victoria Street
Darlinghurst NSW 2010
Australia
Commercial sector/Industry
Merck Healthcare KGaA
Frankfurter Str. 250
64293 Darmstadt

Germany
Commercial sector/Industry
Roche Products Pty Limited
Level 8, 30-34 Hickson Road
Sydney NSW 2000
Australia