Trametinib With GSK2141795 in BRAF Wild-type Melanoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by University of California, San Francisco
Sponsor:
Collaborator:
National Comprehensive Cancer Network
Information provided by (Responsible Party):
Adil Daud, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01941927
First received: August 30, 2013
Last updated: October 25, 2013
Last verified: September 2013
  Purpose

This is a multicenter phase II clinical study of trametinib in combination with GSK2141795 in patients with BRAF wild-type mutation melanoma. All patients will receive continuous dosing of trametinib (2 mg) in combination with GSK2141795 (25 mg) oral daily until progression of disease, withdrawal of consent, or the development of intolerable treatment associated toxicity. Imaging (CT or MRI) will be performed within 7 days prior to day 1 of Odd Cycles, starting with Cycle 3.

Patients may continue treatment with trametinib in combination with GSK2141795 on trial until disease progression or the development of unacceptable toxicity that does not improve with maximal supportive care or dose reduction per protocol.

Treatment-associated adverse events will be assessed based on clinical and laboratory findings using the Common Toxicity Criteria for Adverse Events, version 4.0. Adverse event assessments will be performed every week through cycle 3 day 1, and on day 1 for every cycle thereafter. AEs and SAEs will be monitored by UCSF's Data Safety Monitoring Committee.

Safety assessments will include medical history, physical examination, CBC with differential, chemistries panel, thyroid function and pregnancy tests, ECGs, and ophthalmology evaluations. Screening assessments will also include a transthoracic echocardiogram or MUGA scan, and brain imaging.

It is estimated that 48 patients will complete the study.


Condition Intervention Phase
Melanoma
Drug: Trametinib (GSK1120212)
Drug: GSK2141795
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Clinical Trial of the MEK Inhibitor Trametinib With the AKT Inhibitor GSK2141795 in BRAF Wild-type Melanoma

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Objective Response Rate (ORR) in patients with either mutated NRAS or wild-type NRAS/wild-type BRAF melanoma treated with the combination of trametinib and GSK 2141795 [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Progression-Free Survival of patients treated with the combination of trametinib and GSK 2141795 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Overall Survival of patients treated with the combination of trametinib and GSK 2141795 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Time-to-Progression of patients treated with the combination of trametinib and GSK 2141795 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Number of severe adverse events (Grade 3 and 4) reported by patients related with the treatment of Trametinib and GSK2141795. [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    SAEs will be collected to assess the tolerability, safety and toxicity profile of this treatment.


Other Outcome Measures:
  • Biomarkers of response in biopsy tissue from patients on trial [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Biomarkers of response in peripheral blood from patients on trial [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Biomarkers of resistance in biopsy tissue from patients on trial [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Biomarkers of resistance in peripheral blood from patients on trial [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: September 2013
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Trametinib, GSK2141795

Trametinib (GSK1120212)

  • Oral
  • 2 mg
  • Daily
  • Number of Cycles: until progression or unacceptable toxicity develops

GSK2141795

  • Oral
  • 25 mg
  • Daily
  • Number of Cycles: until progression or unacceptable toxicity develops
Drug: Trametinib (GSK1120212) Drug: GSK2141795

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 18 years.
  2. Histologically or cytologically confirmed Malignant Melanoma.
  3. Unresectable Stage III or Stage IV disease.
  4. Measureable disease by RECIST 1.1
  5. ECOG performance status 0-2
  6. Resolution of all acute toxic effects of prior radiotherapy, chemotherapy or surgical procedures to NCI CTCAE Version 4.0 grade ≤1. At least 2 weeks must have elapsed since the end of prior systemic treatment, radiotherapy, or major surgical procedure.
  7. Evidence of tumor DNA showing either NRAS mutation or NRAS WT/BRAF WT. BRAF genotype must be determined by a CLIA-approved assay. NRAS genotyping may be determined by Sanger sequencing, melting point PCR assay, Sequenome, or NextGen sequencing.
  8. Adequate Bone Marrow and Organ function as defined:

    • Hemoglobin ≥ 9 g/dL
    • Absolute neutrophil count ≥ 1,500/mm3
    • Platelet count ≥ 100,000/mm3
    • Bilirubin ≤ 1.5 times normal limit
    • AST/ALT ≤ 5 times the upper limit of normal if liver metastasis present or ≤2.5 X ULN if no liver metastases are present.
    • Creatinine ≤ 2 mg/dL

Exclusion Criteria:

  1. Progressive CNS metastatic disease. Patients with CNS metastases are allowed only if previously treated and stable for 8 weeks or more, and patient is neurologically intact off steroids. The stability must be documented by MRI/CT over a period of 8 weeks or greater.
  2. Congestive Heart Failure with significant limitation of activity New York Heart Association (NYHA) class III or IV
  3. Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism.
  4. QTc >480 mSec , unless presence of bundle branch block. In this case, observed QTc - (QRS-150) should be ≤ 480 msec.
  5. More than 1 prior chemotherapy regimen. Patients may have had any prior immunotherapy regimens but must be at least 6 weeks out from anti-CTLA4 or anti-PD-1 antibody treatment and show progression based on immune response evaluation criteria.
  6. Pregnancy or breastfeeding. Female subjects must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy and for 4 months following last dose.
  7. Prior treatment with any AKT or MEK inhibitor
  8. Retinal or Fundal disease (including macular degeneration, retinal vein occlusion, hypertensive or diabetic retinopathy).
  9. Inflammatory Bowel Disease, malabsorption syndrome or diarrhea > Grade 1.
  10. Need for treatment with drugs that are known potent CYP3A inhibitors. Current use or anticipated need for treatment with drugs that are known potent CYP3A or CYP1A2 inducers.
  11. Prior malignancy will be allowed as long as the patient is known to be free of disease for at least 5 years. Prior SCC, Basal Cell, cervical cancer, early stage prostate cancer, DCIS or melanoma (second primary) are allowed even if <5 years from diagnosis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01941927

Contacts
Contact: Jade Yen 415-885-7837 YenJ@cc.ucsf.edu

Locations
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94115
Contact: Jade Yen    415-885-7837    YenJ@cc.ucsf.edu   
Principal Investigator: Adil Daud, M.D.         
Sub-Investigator: Alain Algazi, M.D.         
Sub-Investigator: Michelle Ashworth, M.D.         
Sub-Investigator: Susana Ortiz, M.D.         
Sponsors and Collaborators
Adil Daud
National Comprehensive Cancer Network
Investigators
Principal Investigator: Adil Daud, M.D. University of California, San Francisco
  More Information

No publications provided

Responsible Party: Adil Daud, Clinical Professor, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01941927     History of Changes
Other Study ID Numbers: 13855
Study First Received: August 30, 2013
Last Updated: October 25, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, San Francisco:
Melanoma
Wild-type
BRAF

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Trametinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014