AzTrials
AzTrials

Metastatic MelanomaPhase 1/2CombiRTNCT02392871

Radiotherapy & Combi in Metastatic Melanoma

A Phase 1/2 study testing Palliative radiotherapy and Dabrafenib and trametinib (combination) in people with Metastatic Melanoma, run by Melanoma and Skin Cancer Trials Limited at 3 sites in Australia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to investigate the side effects and safety, and effectiveness of combining dabrafenib and trametinib with radiotherapy. Previous and ongoing clinical trials have demonstrated the effectiveness and safety of combining both dabrafenib and trametinib compared with dabrafenib alone. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Melanoma
What is being tested?
Palliative radiotherapy and Dabrafenib and trametinib (combination)
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
3 sitesAustralia
Study dates
May 2015to 17 Apr 2020
Phase
Phase 1/2
Are there results?
None posted in the registry

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

  • ≥18 years of age.
  • Signed written informed consent.
  • Histologically confirmed cutaneous melanoma that is either Stage IIIC (unresectable) or Stage IV (metastatic), and determined to be BRAF V600E/K mutation-positive as determined by a BRAF mutation assay.
  • Note: For Stage IIIC disease, the decision that the disease is unresectable should be formally endorsed by the melanoma multidisciplinary tumour board of the local institution.
  • Have received dabrafenib and trametinib for 2 weeks or more prior to enrolment in the study (i.e. first fraction of palliative RT), and is still continuing with dabrafenib and trametinib.
  • Symptomatic or bulky (greater than 2 cm in diameter) soft tissue, nodal or bony metastases requiring palliative RT.
Show all 12Show fewer
  • Have measurable disease according to RECIST 1.1 criteria. Note: patients with bony metastases that are not measurable by RECIST 1.1 criteria are allowed in this study.
  • All anti-cancer treatment-related toxicities (except alopecia and laboratory values as listed on Table 1 in protocol) must be less than or equal to (≤) Grade 1 according to the Common Terminology Criteria for Adverse Events version 4 (CTCAE version 4.03; NCI, 2009) at the time of study enrolment.
  • 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.
  • Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to enrolment and agree to use effective contraception, from 14 days prior to enrolment throughout the treatment period, and for 4 months after the last dose of study treatment.
  • An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Adequate baseline organ function (as defined in Table 1 in protocol).

Who cannot join

  • Treatment with Ipilimumab or any other anti-CTLA-4 monoclonal antibody therapy within the past 4 weeks.
  • Treatment with anti-PD-1 or anti-PD-L1 monoclonal antibody therapy within the past 4 weeks.
  • Known ocular or primary mucosal melanoma.
  • Four (4) or more lesions requiring palliative RT at the time of study enrolment.
  • Symptomatic brain metastases or those treated < 3 months previously.
  • Clear evidence of systemic disease progression on dabrafenib and trametinib.
Show all 28Show fewer
  • Systemic anti-cancer treatment (chemotherapy, immunotherapy, biologic therapy, vaccine therapy, or investigational treatment) within the last 4 weeks. Prior interferon treatment in the adjuvant setting is allowed.
  • Note: Tamoxifen and aromatase inhibitors are allowed in the adjuvant setting of breast cancer.
  • Current use of a prohibited medication (list of prohibited medications in protocol).
  • History of malignancy other than disease under study within 3 years of study enrolment with exceptions below, or any malignancy with confirmed activating RAS mutation.
  • Note: Prospective RAS testing is not required. However, if the results of previous RAS testing are known, they must be used in assessing eligibility.
  • Exception: Subjects who have been disease-free for 3 years, or subjects with a history of completely resected non-melanoma skin cancer.
  • Any serious or unstable pre-existing medical conditions (aside from malignancy exceptions specified above), psychiatric disorders, or other conditions that could interfere with the subject's safety, obtaining informed consent, or compliance with study procedures.
  • A history of known Human Immunodeficiency Virus (HIV).
  • A history or evidence of cardiovascular risk including any of the following:
  • A QT interval corrected for heart rate using the Bazett's formula (QTcB) ≥ 480 msec;
  • A history or evidence of current clinically significant uncontrolled arrhythmias;
  • A history of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within 6 months prior to enrolment;
  • A history or evidence of current ≥ Class II congestive heart failure as defined by the New York Heart Association (NYHA) guidelines;
  • Patients with intra-cardiac defibrillators;
  • Abnormal cardiac valve morphology (≥ grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study). Subjects with moderate valvular thickening should not be entered on study; g. Treatment refractory hypertension defined as a blood pressure of systolic> 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy; h. Known cardiac metastases.
  • A history of retinal vein occlusion (RVO).
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study treatments, their excipients, and/or dimethyl sulfoxide (DMSO).
  • Pregnant or nursing females.
  • Previous RT to the same lesion or area due to receive the current course of palliative RT.
  • Note: patients who had previous RT to other areas are eligible to the study if the previous RT was completed more than 8 weeks prior.
  • A history of autoimmune diseases which are known to increase radiation toxicity, including systemic lupus erythematosus and scleroderma.
  • Genetic syndromes exhibiting increased radiosensitivity (e.g. ataxia telangiectasia).

Trial locations and contacts

3 sites in 1 country.

Australia3 sites

  • Princess Alexandra Hospital

    Brisbane, Queensland, 4102

  • St Vincent's Hospital

    Darlinghurst, New South Wales, 2010

  • Westmead Hospital

    Sydney, New South Wales, 2145

Other trials in Australia

About this study

Official title: An Open-label, Single-arm, Phase I/II, Multicentre Study to Evaluate the Safety and Efficacy of the Combination of Dabrafenib, Trametinib and Palliative Radiotherapy in Patients with Unresectable (stage IIIc) and Metastatic (stage IV) BRAF V600E/K Mutation-positive Cutaneous Melanoma

The purpose of this study is to investigate the side effects and safety, and effectiveness of combining dabrafenib and trametinib with radiotherapy.

Previous and ongoing clinical trials have demonstrated the effectiveness and safety of combining both dabrafenib and trametinib compared with dabrafenib alone. This has led to the approval for the use of both drugs in combination in people with metastatic melanoma with the BRAF mutation. Melanoma that has spread to other parts of the body may also benefit from radiotherapy to help reduce symptoms from melanoma. Previous studies have shown that melanoma may be sensitive to radiotherapy and that it can help to improve quality of life.

The intention of the CombiRT study is to establish if dabrafenib, trametinib and radiotherapy combined is a safe and effective treatment for metastatic melanoma.

Being tested
Palliative radiotherapy, Dabrafenib and trametinib (combination)
Keywords
Metastatic melanoma, Palliative radiotherapy
Medical subject headings
Melanoma

What participants receive

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

  • Palliative radiotherapyRadiation

  • Dabrafenib and trametinib (combination)Drug

    Patients should be taking dabrafenib and trametinib for at least 2 weeks prior to enrolment into the study.

Study groups in NCT02392871
Study groupRoleWhat they receive
RadiotherapyExperimentalPalliative radiotherapy in combination with dabrafenib and trametinib Eligible subjects are patients who have been on dabrafenib and trametinib for more than 2 weeks, as the current standard management for advanced stage melanoma. Palliative RT will be delivered to symptomatic or bulky (>2cm) soft tissue, nodal or bony metastases concurrently with dabrafenib and trametinib. Up to 3 areas of disease can be irradiated at the same time. Following RT, dabrafenib and trametinib alone will be continued until disease progression according to RECIST 1.1 criteria.
Receives: Radiation: Palliative radiotherapy; Drug: Dabrafenib and trametinib (combination)

What is being measured

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

  1. Toxicity profile for patients receiving dabrafenib and trametinib in combination with RT, by measuring adverse events and radiotherapy associated toxicities.

    Measured: 0-12 months

Secondary outcomes (4)

  1. Patients' pain using a visual analog scale (questionnaire)

    Measured: 0-12 months

  2. Overall disease response by measuring progression free survival and overall survival.

    Measured: 0-12 months

  3. Local treatment response in the irradiated index lesion(s).

    Measured: 0-12 months

  4. Time to local progression in the irradiated index lesion(s).

    Measured: 0-12 months

Timeline

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

  1. First posted19 Mar 2015 (estimated)
  2. Study startMay 2015
  3. Primary completion23 Sep 2019
  4. Study completion17 Apr 2020

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02392871
Sponsor's protocol ID
02.14
Acronym
CombiRT
Status last verified
Nov 2024
First submitted
10 Mar 2015
Last updated
27 Nov 2024
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Palliative radiotherapy and Dabrafenib and trametinib (combination) in people with Metastatic Melanoma, run by Melanoma and Skin Cancer Trials Limited at 3 sites in Australia.

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 12 inclusion and 28 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: finished, as of the sponsor's last update on 27 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Australia. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Toxicity profile for patients receiving dabrafenib and trametinib in combination with RT, by measuring adverse events and radiotherapy associated toxicities. (time frame: 0-12 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 NCT02392871.

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 27 Nov 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in