Health TrialsbyHealthPanel

Circulating Tumour DNA Guided Adaptive BRAF and MEK Inhibitor Therapy

ConditionMelanoma
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorThe Christie NHS Foundation Trust

About this trial

The goal of this clinical trial is to investigate adaptive therapy in late-stage cutaneous melanoma. The main question it aims to answer are:

If the patient having breaks in their treatment allows the less resistant cells to continue to grow, this would result in a tumour with a lower proportion of resistant cells, making the tumour less resistant to the treatment, an increasing the time it takes for the disease to progress?

Participants will

* Receive their allocated treatment regimen until their cancer progresses, they or their doctor withdraw them from the study, or until the study ends, whichever happens first. * Attend fortnightly visits to hospital. * Complete EORTC QLQ-C30 and PRO-CTCAE questionnaires, prior to treatment, every 12 weeks and at the point of cancer progression, to assess quality of life.

Researchers will compare the adaptive therapy participant arm with a standard of care arm to answer the research question described above.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Written and informed consent obtained from participant and agreement of participant to comply with the requirements of the study

Histological confirmation of cutaneous melanoma

≥ 18 years of age

Stage III un-resectable/ IV disease

Disqualifiers

Prior systemic targeted BRAF/MEKi therapy for stage IV (metastatic) melanoma (treatment for stage III allowed as long as RFS ≥26 weeks following discontinuation of drugs)

BRAF wild-type malignant melanoma

Metastasis to the brain or leptomeninges

Any contraindication to treatment with encorafenib or binimetinib as per the local Summary of Product Characteristics

Trial design

Design model

Parallel

Treatments tested in this trial

  • Adaptive Therapy

    Drug

    A blood test that measures the amount of tumour DNA circulating in the patient's blood (known as ctDNA) will be conducted every two weeks to check if the cancer cells are still present, and if they are becoming active. The result of this test will allow doctors to monitor the activity of the tumour and judge when to pause and resume encorafenib and binimetinib treatment. This intermittent treatment is called 'adaptive therapy'.

  • Standard of Care

    Drug

    Encorafenib and binimetinib delivered to UK standard of care.

Treatment groups

40 Participants
are divided into 2 treatment groups
Group A: ARM A: Standard of careActive comparator 1 intervention
Group B: ARM B: Adaptive therapyExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

To measure tumour response to re-introduction of encorafenib plus binimetinib following the first "drug off " period.

Specific measure: Maximal reduction in percentage ctDNA mutant BRAF copies/ml of plasma from baseline 2 TAB level upon restart of E+B following first drug off period.

Time frame
3 years (Longitudinally throughout the study)

Secondary outcomes

1

To measure the thresholds of percentage reduction in TAB level in ctDNA as a measure of response to stop drugs and the percentage increase in TAB as a decision to restart drugs.

Specific measure: ctDNA mutant BRAF copies/ml of plasma

Time frame
3 years (Longitudinally throughout the study)
2

To measure maximal response (complete response (CR)/partial response (PR)/stable disease (SD)/progressive disease (PD)) to therapy in Arm A vs. Arm B

Specific measure: Maximal radiological response (complete response (CR)/partial response (PR)/stable disease (SD)/progressive disease (PD)) using RECIST v1.1 criteria

Time frame
Randomisation until RECIST progression/clinical deterioration (estimated 12 months)
3

To measure progression free survival (PFS) in Arm A vs. Arm B

Specific measure: Percentage of participants who have experienced disease progression or death. PFS defined as time from randomisation to radiological (RECIST v1.1 and in Arm B defined as radiological progression whilst on targeted therapy unless stopped due to toxicity/choice) progression

Time frame
3 years (Continuously throughout the study)
4

To measure time to clinical deterioration in Arm A vs. Arm B.

Specific measure:Time to clinical deterioration. Defined as either the point of radiological progression (defined as per RECIST v1.1) or in participants treated beyond radiological progression, at the time of clinically determined deterioration defined at the discretion of the treating clinician, specifically due to progression of the underlying cancer

Time frame
3 years (Continuously throughout the study)

Other outcomes

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

The Christie NHS Foundation Trust

Lead sponsor

University of Manchester

Collaborator

University of Liverpool

Collaborator

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: