A study of GSK1120212 compared with chemotherapy in patients with BRAF mutation positive advanced or metastatic melanoma

Phase 1

• Conditions: Advanced or metastatic BRAF V600E/K mutation-positive melanoma; MedDRA version: 14.1Level: LLTClassification code 10027481Term: Metastatic melanomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

• Registration Number: EUCTR2010-022838-85-CZ
• Lead Sponsor: GlaxoSmithKline Research and Development Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-12-09
• Last Update Posted: 31 January 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 297

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 210
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 87

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 details
13. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drug, or excipients or to dimethyl sulfoxide (DMSO) or to Cremophor EL (polyoxyethylated castor oil).
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Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified