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MelanomaPhase 2NCT02974803

Concurrent Dabrafenib + Trametinib With Sterotactic Radiation in BRAF Mutation-Positive Malignant Melanoma and Brain Metastases

A Phase 2 study testing Dabrafenib and Trametinib in people with Melanoma and Brain Metastases, run by Canadian Cancer Trials Group at 6 sites in Canada.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Dabrafenib and trametinib are drugs that are usually given for the treatment of melanoma. Combinations of dabrafenib and trametinib have also been studied and when used together have shown to increase tumour shrinkage in animals compared to either drug alone. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma, Brain Metastases
What is being tested?
Dabrafenib and Trametinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
6 sitesCanada
Study dates
9 Feb 2018to 29 Jul 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed melanoma metastatic to brain and determined to be BRAF V600 mutated.
  • Age ≥ 18 years.
  • Karnofsky Performance Status of 70-100 (Appendix I).
  • Patients must have a life expectancy of at least 12 weeks.
  • Presence of measurable disease (i.e. present with at least one measurable CNS lesion per RECIST 1.1).
  • Presence of 1-10 brain metastases as confirmed on a thin slice axial T1 post-gadolinium MRI sequence. The maximum diameter of a single brain lesion should be ≤ 4 cm and presence of a measurable lesion ≥ 1cm based on baseline MRI of brain.
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  • All CNS metastases amenable to single fraction SRS and or fractionated SRS. Hemorrhagic lesions are allowed if the treating radiation oncologist deems the lesion amenable to focal SRS.
  • Able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
  • Laboratory requirements (within 14 days prior to registration):
  • ANC ≥ 1.2 x 10^9/L
  • Hemoglobin ≥ 90 g/L
  • Platelet count ≥ 100 x 10^9/L
  • PT/INR \& PTT ≤ 1.3 x ULN
  • Total bilirubin ≤ 1.5 x ULN
  • AST and ALT ≤ 2.5 x ULN
  • Serum creatinine or ≤ 1.5 x ULN or Creatinine Clearance ≥ 50 ml/min (calculated by Cockcroft and Gault)
  • LVEF ≥ LLN (within 28 days prior to registration)
  • No prior treatment with a BRAF inhibitor or MEK inhibitor.
  • No known ocular or primary mucosal melanoma.
  • No prior systemic anti-cancer treatment within the last 2 weeks preceding the frist dose of dabrafenib and trametinib. Patients must have recoved from clinical manifestations of toxicity related to prior systemic therapy and have adequate washout as follows: Longest of one of the following:
  • two weeks
  • 5 half-lives for investigational agents
  • Standard cycle length of standard therapies
  • Prior systemic treatment in the adjuvant setting is allowed.
  • No current use of a prohibited medication as described in section 7.2.
  • No history of malignancy with confirmed activating RAS mutation at any time.
  • No history of malignancy other than disease under study within 3 years of study enrollment.
  • No leptomeningeal metastases or metastases causing spinal cord compression that are symptomatic or untreated or not stable for ≥ 3 months. Subjects on stable dose of corticosteroids > 2 weeks or who have been off of corticosteroids for at least 2 weeks can be enrolled with approval of CCTG.
  • No serious or unstable pre-existing medical conditions, psychiatric disorders or other conditions that could interfere with the subject's safety, obtaining informed consent or compliance with study procedures.
  • No history of Hepatitis B Virus or Hepatitis C Virus infection
  • No history or evidence of cardiovascular risk No history or current eveidence/risk of retinal vein occlusion or central serous retinopathy
  • No known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study treatments, their excipients, and/or dimethyl sulfoxide.
  • No pregnant or lactating women.
  • No hisotry of interstitial lung disease or active pneumonitis.
  • Presence of any one brain metastases >4cm in maximal diameter, and/or presence of brain metastase of less than 1cm.
  • No prior whole brain radiation
  • No brainstem metastses
  • No contrindications to MRI and/or Gadolinimum contrast or sterotactic brain radiation therapy.

Who cannot join

None listed.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

Canada6 sites

  • QEII Health Sciences Centre

    Halifax, Nova Scotia, B3H 1V7

  • Juravinski Cancer Centre at Hamilton Health Sciences

    Hamilton, Ontario, L8V 5C2

  • Saskatoon Cancer Centre

    Saskatoon, Saskatchewan, S7N 4H4

  • Centre hospitalier universitaire de Sherbrooke

    Sherbrooke, Quebec, J1H 5N4

  • Odette Cancer Centre

    Toronto, Ontario, M4N 3M5

  • University Health Network

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: A Phase II Study of Concurrent Dabrafenib and Trametinib With Stereotactic Radiation in the Management of Patients With BRAF Mutation-Positive Malignant Melanoma and Brain Metastases

Dabrafenib and trametinib are drugs that are usually given for the treatment of melanoma. Combinations of dabrafenib and trametinib have also been studied and when used together have shown to increase tumour shrinkage in animals compared to either drug alone. Dabrafenib and trametinib have also shown potential to penetrate the blood-brain-barrier when given together and have an effect on brain metastases. Giving these drugs at the same time and then giving brain stereotactic radiosurgery (SRS) may also be preferred in patients with brain metastases

Read the detailed description

The purpose of this study is to find out the effects of giving dabrafenib in combination with trametinib continuously with stereotactic radiotherapy (SRS) has on melanoma and brain metastases.

Stereotactic Radiosurgery (SRS) is a non-surgical radiation therapy used to treat tumours of the brain. It can deliver precisely targeted radiation. Currently SRS alone is the usual treatment for patients with up to 4 brain lesions. This study will include 2 groups 1) patients with 1-4 brain lesions treated with SRS concurrently with dabrafenib and trametinib and 2) patients with 5-10 brain lesions treated with SRS concurrently with dabrafenib and trametinib.

Being tested
Dabrafenib, Trametinib
Medical subject headings
Melanoma, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DabrafenibDrug

    Dabrafenib 150 mg twice a day until progression or unaccepted toxicity.

  • TrametinibDrug

    Trametinib 2 mg once daily until progression or unaccepted toxicity.

Study groups in NCT02974803
Study groupRoleWhat they receive
Dabrafenib and TrametinibExperimentalDabrafenib, PO, 150mg BID Continuously Trameteinib, PO 2mg OD Continuously
Receives: Drug: Dabrafenib; Drug: Trametinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Intracranial Objective Response Rate

    Measured: 24 months

Secondary outcomes (4)

  1. Extra-cranial Objective Response Rate

    Response will be assessed using RECIST v1.1

    Measured: 24 months

  2. Duration of Response

    Response will be assessed using RECIST v1.1

    Measured: 24 months

  3. Intracranial Progression Free Survival

    Response will be assessed using RECIST v1.1

    Measured: 24 months

  4. Overall Progression Free Survival

    Response will be assessed using RECIST v1.1

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Nov 2016 (estimated)
  2. Study start9 Feb 2018
  3. Primary completion29 Jul 2020
  4. Study completion29 Jul 2020

Why it stopped: Very slow accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02974803
Sponsor's protocol ID
I224
Status last verified
Jul 2021
First submitted
23 Nov 2016
Last updated
20 Aug 2021
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dabrafenib and Trametinib in people with Melanoma and Brain Metastases, run by Canadian Cancer Trials Group at 6 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 38 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 20 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Intracranial Objective Response Rate (time frame: 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02974803.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2021.

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