MEK114267, A Phase III randomized, open-label study comparing GSK1120212 to chemotherapy in subjects with advanced or metastatic BRAF V600E/K mutation-positive melanoma

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2010-022838-85-NO
• Date of registration: 17/12/2010
• Prospective Registration: No
• Primary sponsor: GlaxoSmithKline Research and Development Limited
• Public title: MEK114267, A Phase III randomized, open-label study comparing GSK1120212 to chemotherapy in subjects with advanced or metastatic BRAF V600E/K mutation-positive melanoma
• Scientific title: MEK114267, A Phase III randomized, open-label study comparing GSK1120212 to chemotherapy in subjects with advanced or metastatic BRAF V600E/K mutation-positive melanoma
• Date of first enrolment: 15/12/2010
• Target sample size: 297
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-022838-85
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: yes; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Czech Republic, Germany, Greece, Italy, Norway, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects eligible for enrolment in the study must meet all of the following criteria:

1. Signed written informed consent.
2. =18 years of age.
3. Histologically confirmed, Stage III unresectable (Stage IIIc) or metastatic (Stage IV) cutaneous melanoma which is also determined to be BRAF V600E/K mutation-positive by the central laboratory.
4. Subjects may have received no prior treatment or up to one prior regimen of chemotherapy for advanced or metastatic melanoma. Prior treatment with immunotherapy (with the exception of prior ipilimumab, which is only allowed if given in the adjuvant setting), cytokine therapy, biological or vaccine regimen is permitted. Prior use of sorafenib is allowed.
5. Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) [Eisenhauer, 2009].
6. All prior treatment- related toxicities must be CTCAE (Version 4.0) = Grade 1 (except alopecia) at the time of randomization.
7. Able to swallow and retain oral medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
8. Women of childbearing potential and men with reproductive potential must agree to use effective contraception during the study. Additionally women of childbearing potential must have a negative serum pregnancy test within 14 days prior to randomization.
9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 [Oken, 1982].
10. Adequate screening organ function
11. French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Subjects meeting any of the following criteria must not be enrolled in the study:
1. Any prior use of:
• BRAF inhibitors or MEK inhibitors.
• Ipilimumab in the advanced or metastatic setting.

2. Subjects who have received dacarbazine or paclitaxel prior to randomization will not be eligible to receive the same chemotherapy as study medication (i.e. a subject who received prior dacarbazine cannot receive dacarbazine on this trial and would thus receive paclitaxel if randomized to the control arm).

3. Any major surgery, extensive radiotherapy, chemotherapy with delayed toxicity, biologic therapy or immunotherapy within the last 21 days. Chemotherapy given daily or weekly without the potential for delayed toxicity within the last 14 days.

4. Administration of an investigational drug within 28 days or 5 half-lives, (whichever is shorter), prior to randomization – at least 14 days must have passed between the last dose of the prior investigational anti-cancer drug and randomization.

5. Current use of any prohibited medication (see Section 6).

• Use of anticoagulants such as warfarin is permitted, however INR must be monitored in accordance with local institutional practice.

6. History of another malignancy.
Exception: Subjects disease-free for 3 years, or subjects with history of completely resected non-melanoma skin cancer or succesfully treated in situ carcinoma are eligible. Subjects with second malignancies that are indolent or definitely treated may be enrolled. Consultation with GSK Medical monitor is possible.

7. Any serious and/or unstable pre-existing medical (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject’s safety, obtaining informed consent or compliance to the study procedures.

8. Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (with the exception of chronic or cleared HBV and HCV infection which will be allowed).

9. Brain metastases with the following exceptions that are ALL confirmed by the GSK Medical Monitor: All known lesions must be previously treated with surgery or stereotactic radiosurgery, and Brain lesion(s), if still present, must be confirmed stable (i.e. no increase in lesion size) for =90 days prior to randomization (must be documented with two consecutive MRI or CT scans using contrast), and asymptomatic with no corticosteroids requirement for = 30 days prior to randomization, and no enzyme-inducing anticonvulsants for = 30 days prior to randomization.
10. History or evidence of cardiovascular risk including any of the following: QTcB = 480 msec, or history or evidence of current clinically significant uncontrolled arrhythmias (exception: subjects with controlled Atrial Fibrillation for > 30 days prior to randomisation), or history of acute coronay syndromes, coronary angioplasty, or stenting within 6 months prior to randomisation, or history/evidence of current =Class II congestive heart failure as defined by NYHA.
11. History of interstitial lung disease or pneumonitis.
12. History or current evidence / risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) - see protocol for detail

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Advanced or metastatic BRAF V600E/K mutation-positive melanoma
MedDRA version: 12.1 Level: LLT Classification code 10027481 Term: Metastatic melanoma

Intervention(s)

Product Name: GSK1120212
Product Code: GSK1120212
Pharmaceutical Form: Film-coated tablet
CAS Number: 871700-17-3
Current Sponsor code: GSK1120212
Other descriptive name: GSK1120212B
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-

Product Name: GSK1120212
Product Code: GSK1120212
Pharmaceutical Form: Film-coated tablet
CAS Number: 871700-17-3
Current Sponsor code: GSK1120212
Other descriptive name: GSK1120212B
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1.0-

Product Name: GSK1120212
Product Code: GSK1120212
Pharmaceutical Form: Film-coated tablet
CAS Number: 871700-17-3
Current Sponsor code: GSK1120212
Other descriptive name: GSK1120212B
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.0-

Primary Outcome(s)

Secondary Objective: Efficacy:
- To further characterize the efficacy in the total population with respect to overall survival, overall response rate, and duration of response
- To characterize PFS in the subgroup of subjects that have received no prior chemotherapy in the advanced or metastatic setting and the subgroup who have received one prior chemotherapy in the advanced or metastatic setting
- To characterize PFS and overall response rate in the subgroup of subjects with BRAF V600 K mutation-positive melanoma
- To characterize efficacy (PFS, overall response rate, and duration of response) in subjects following crossover from chemotherapy to GSK1120212

The safety objective is to evaluate the safety and tolerability of GSK1120212 administered as a single agent for advanced or metastatic melanoma.

A BRAF mutation assay is under development and further validation will be performed
in this study.

Main Objective: The primary objective for this study is to establish the superiority of GSK1120212 over chemotherapy with respect to progression-free survival for subjects with advanced/metastatic BRAF V600E/K mutation-positive melanoma

Primary end point(s): The primary endpoint of this study will be progression free survival based on investigator assessments, defined as the time from randomization until the earliest date of disease progression or death due to any cause.

Secondary ID(s)

MEK114267

2010-022838-85-DE

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 30/11/2017
• Date Completed: 16/12/2016
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-022838-85/results