Trametinib With GSK2141795 in BRAF Wild-type Melanoma
| Status: | Recruiting |
|---|---|
| Conditions: | Skin Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 2/8/2015 |
| Start Date: | September 2013 |
| End Date: | May 2018 |
| Contact: | Jade Yen |
| Email: | YenJ@cc.ucsf.edu |
| Phone: | 415-885-7837 |
Phase II Clinical Trial of the MEK Inhibitor Trametinib With the AKT Inhibitor GSK2141795 in BRAF Wild-type Melanoma
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.
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.
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
We found this trial at
1
site
1600 Divisadero Street
San Francisco, California 94115
San Francisco, California 94115
888.689.8273
UCSF Helen Diller Family Comprehensive Cancer Center UCSF’s long tradition of excellence in cancer research...
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