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Dabrafenib and Trametinib for BRAF-inhibitor Pretreated Patients | Clinical Trials | Clareo Health

COMPLETEDPHASE2

Dabrafenib and Trametinib for BRAF-inhibitor Pretreated Patients

A Phase II Clinical Trial on the Combination of Dabrafenib and Trametinib for BRAF-inhibitor Pretreated Patients With Advanced BRAF V600 Mutant Melanoma

NCT02296996•Universitair Ziekenhuis Brussel

View on ClinicalTrials.gov

Summary

Patients with BRAF V600 mutant advanced melanoma benefit from treatment with a BRAF-inhibitor (e.g. dabrafenib, vemurafenib) and from combination of a BRAF- and MEK-inhibitor (e.g. dabrafenib and trametinib). Following initial tumor regression, progression is diagnosed in a majority of patients treated with BRAF-inhibitor mono-therapy within the first 12-months of therapy. Various molecular mechanisms that underlie the development of resistance to treatment with a BRAF-inhibitor have been reported. These mechanisms do not include secondary mutations in the BRAF-gene and therefore resistance to BRAF-inhibition could potentially be reversible when selective pressure by BRAF-inhibition is withheld for a sufficient period of time of melanoma progression. This clinical trial protocol addresses the potential renewed anti-tumor activity of combined BRAF- and MEK inhibition with the combination of dabrafenib and trametinib in patients with unresectable AJCC stage III or - IV BRAF V600 mutant melanoma who are documented with progression of disease at least 12 weeks following the last day of dosing of a BRAFinhibitor containing treatment regimen.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. 18 years of age and signed written informed consent.
•2. Histologically confirmed cutaneous melanoma that is either Stage IIIC (unresectable) or Stage IV (metastatic), and determined to be BRAF V600E/K mutation-positive.
•3. Subjects must have failed at least two prior systemic anti-cancer treatments for Stage IIIC (unresectable) or Stage IV (metastatic) melanoma that must have included:
•* Treatment with a BRAF inhibitor (including but not limited to dabrafenib, vemurafenib, and LGX818) and progression of disease per RECIST, version 1.1 \[Eisenhauer, 2009\] must have been documented during this treatment.
•* Treatment with ipilimumab (or an alternative experimental immunotherapy) and progression of disease per immune related response criteria \[Wolchock Clin Cancer Res December 1, 2009 15; 7412\] must have been documented during this treatment.
•4. Documented progression of disease per RECIST, version 1.1 \[Eisenhauer, 2009\]) or per immune related response criteria \[Wolchock Clin Cancer Res December 1, 2009 15; 7412\] if the latest systemic therapy administered was ipilimumab, an anti-PD1 or anti-PD-L1 therapy, or any other experimental immunotherapy.
•5. The presence of at least one measurable lesion per RECIST, version 1.1 \[Eisenhauer, 2009\]).
•6. Interval between the date of the last administration of prior therapy for melanoma and the date of recruitment:
•* \> 12 weeks following the date of the last administration of a BRAF-inhibitor;
•* \> 12 weeks following the date of the first administration and \> 4 weeks following the date of the last administration of ipilimumab, or an anti-PD1, or anti-PD-L1 therapy;
+2 more criteria

Exclusion Criteria

•8. All prior anti-cancer treatment-related toxicities (except alopecia and laboratory values as listed on Table 2) must be ≤ Grade 1 according to the Common Terminology Criteria for Adverse Events version 4 (CTCAE version 4.0; National Cancer Institute ( NCI,) 2009) at the time of recruitment.
•9. 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.
•10. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to recruitment and agree to use effective contraception, as defined in Section 7.3.3.1, throughout the treatment period, and for 4 months after the last dose of study treatment.
•11. An Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 \[Oken, 1982\]. Refer to Appendix 1 for details.
•12. Adequate baseline organ function as defined in Table 2.
•1. Grade 4 or repetitive grade 3 adverse event(s) related to prior treatment with a BRAF- and/or MEK inhibitor.
•2. Any contra-indication for evaluation by whole body CT and MRI of the brain.
•3. Taken an investigational drug within 28 days or 5 half-lives (minimum 14 days), whichever is shorter, prior to recruitment.
•4. Current use of a prohibited medication as described in Section 6 or requires any of these medications during treatment.
•5. History of another malignancy, including 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, (i.e. subjects with second malignancies that are indolent or definitively treated at least 3 years ago) not including malignancy with confirmed activating RAS mutation, or subjects with a history of completely resected non-melanoma skin cancer.
+17 more criteria

Locations (1)

UZ Brussel

Brussels, Belgium

Key Dates

Start Date

October 1, 2014

Primary Completion Date

December 1, 2017

Completion Date

December 1, 2017

Last Updated

January 23, 2019

Enrollment

ACTUAL participants

Conditions

Malignant Melanoma

Interventions

Dabrafenib + Trametinib

DRUG

An Phase Ib/II Clinical Trial of TCC1727 Combination Therapy in Advanced Solid Tumors

NCT07371663

Solid CancersNSCLC (Advanced Non-small Cell Lung Cancer)+3 more

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RECRUITINGPHASE1/PHASE2

Modified Vaccine for High Risk or Low Residual Melanoma Patients

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Malignant Melanoma

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: January 23, 2019Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Dabrafenib and Trametinib for BRAF-inhibitor Pretreated Patients

Inclusion Criteria

Exclusion Criteria

An Phase Ib/II Clinical Trial of TCC1727 Combination Therapy in Advanced Solid Tumors

Modified Vaccine for High Risk or Low Residual Melanoma Patients

AMT-253 in Patients With Advanced Solid Tumours

Carbon Ion Radiation Therapy in the Treatment of Mucous Melanomas of the Female Lower Genital Tract

Toripalimab Combined With Radiotherapy and Chemotherapy in the Treatment of SNMM After Endoscopic Surgery

Registry of Subjects at Risk of Pancreatic Cancer