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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02392871




Registration number
NCT02392871
Ethics application status
Date submitted
10/03/2015
Date registered
19/03/2015

Titles & IDs
Public title
Radiotherapy & Combi in Metastatic Melanoma
Scientific 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
Secondary ID [1] 0 0
02.14
Universal Trial Number (UTN)
Trial acronym
CombiRT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Dabrafenib and trametinib (combination)

Experimental: Radiotherapy - Palliative 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.


Treatment: Drugs: Dabrafenib and trametinib (combination)
Patients should be taking dabrafenib and trametinib for at least 2 weeks prior to enrolment into the study.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Toxicity profile for patients receiving dabrafenib and trametinib in combination with RT, by measuring adverse events and radiotherapy associated toxicities.
Timepoint [1] 0 0
0-12 months
Secondary outcome [1] 0 0
Patients' pain using a visual analog scale (questionnaire)
Timepoint [1] 0 0
0-12 months
Secondary outcome [2] 0 0
Overall disease response by measuring progression free survival and overall survival.
Timepoint [2] 0 0
0-12 months
Secondary outcome [3] 0 0
Local treatment response in the irradiated index lesion(s).
Timepoint [3] 0 0
0-12 months
Secondary outcome [4] 0 0
Time to local progression in the irradiated index lesion(s).
Timepoint [4] 0 0
0-12 months

Eligibility
Key inclusion criteria
1. =18 years of age.
2. Signed written informed consent.
3. 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.
4. 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.
5. Symptomatic or bulky (greater than 2 cm in diameter) soft tissue, nodal or bony metastases requiring palliative RT.
6. 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.
7. 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.
8. 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.
9. 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.
10. An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
11. Adequate baseline organ function (as defined in Table 1 in protocol).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Treatment with Ipilimumab or any other anti-CTLA-4 monoclonal antibody therapy within the past 4 weeks.
2. Treatment with anti-PD-1 or anti-PD-L1 monoclonal antibody therapy within the past 4 weeks.
3. Known ocular or primary mucosal melanoma.
4. Four (4) or more lesions requiring palliative RT at the time of study enrolment.
5. Symptomatic brain metastases or those treated < 3 months previously.
6. Clear evidence of systemic disease progression on dabrafenib and trametinib.
7. 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.
8. Current use of a prohibited medication (list of prohibited medications in protocol).
9. 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.
10. 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.
11. A history of known Human Immunodeficiency Virus (HIV).
12. 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.
13. A history of retinal vein occlusion (RVO).
14. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study treatments, their excipients, and/or dimethyl sulfoxide (DMSO).
15. Pregnant or nursing females.
16. 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.
17. A history of autoimmune diseases which are known to increase radiation toxicity, including systemic lupus erythematosus and scleroderma.
18. Genetic syndromes exhibiting increased radiosensitivity (e.g. ataxia telangiectasia).

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
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
1/05/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
17/04/2020
Sample size
Target
Accrual to date
Final
10
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
St Vincent's Hospital - Darlinghurst
Recruitment hospital [2] 0 0
Westmead Hospital - Sydney
Recruitment hospital [3] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2145 - Sydney
Recruitment postcode(s) [3] 0 0
4102 - Brisbane

Funding & Sponsors
Primary sponsor type
Other
Name
Melanoma and Skin Cancer Trials Limited
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Melanoma Institute Australia
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Tim Wang
Address 0 0
Westmead Hospital
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT02392871