Dabrafenib, Trametinib, and Navitoclax in Treating Patients With Solid Tumors That Are Metastatic or Cannot be Removed by Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01989585
First received: November 18, 2013
Last updated: September 16, 2014
Last verified: September 2014
  Purpose

This partially randomized phase I/II trial studies the side effects and best dose of dabrafenib, trametinib, and navitoclax and to see how well they work in treating patients with solid tumors that have spread to other parts of the body or cannot be removed by surgery. Dabrafenib, trametinib, and navitoclax may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.


Condition Intervention Phase
Recurrent Melanoma
Stage IIIA Melanoma
Stage IIIB Melanoma
Stage IIIC Melanoma
Stage IV Melanoma
Unspecified Adult Solid Tumor, Protocol Specific
Drug: dabrafenib
Drug: trametinib
Biological: navitoclax
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of Dabrafenib, Trametinib, and Navitoclax in BRAF Mutant Melanoma and Other Solid Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Recommended phase II dose of the combination of dabrafenib, trametinib, and navitoclax determined by dose-limiting toxicities graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (Phase I) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • Proportion of patients with a CR, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, in the cohort of patients treated with dabrafenib, trametinib, and navitoclax (DTN) (Phase II) [ Time Frame: Up to 4 weeks after last study treatment ] [ Designated as safety issue: No ]
    The proportion of patients with a best response of CR will be presented with a 95% confidence interval calculated using the method of Atkinson and Brown.

  • Maximal degree of tumor regression (Phase II) [ Time Frame: Up to 4 weeks after last study treatment ] [ Designated as safety issue: No ]
    A comparison between the maximal tumor regression for patients treated with DTN and dabrafenib and trametinib (DT) will be conducted using a Wilcoxon rank-sum test.


Secondary Outcome Measures:
  • PFS (Phase II) [ Time Frame: Up to 4 weeks after last study treatment ] [ Designated as safety issue: No ]
    PFS will be summarized using the Kaplan-Meier. Log-rank tests will be used to assess for indications of differences between the two treatment modalities.

  • OS (Phase II) [ Time Frame: Up to 4 weeks after last study treatment ] [ Designated as safety issue: No ]
    OS will be summarized using the Kaplan-Meier. Log-rank tests will be used to assess for indications of differences between the two treatment modalities.

  • ORR (Phase II) [ Time Frame: Up to 4 weeks after last study treatment ] [ Designated as safety issue: No ]
    ORRs will be presented with 95% exact, binomial confidence intervals.


Other Outcome Measures:
  • Change in terminal deoxynucleotidyl transferase 2´-deoxyuridine, 5´-triphosphate (dUTP) nick end labeling assay (TUNEL) staining [ Time Frame: Baseline to up to 1 week ] [ Designated as safety issue: No ]
    Fold changes of TUNEL will be calculated (post/pre). A Wilcoxon rank-sum test will be used to compare the ratios (or equivalently, the difference in the natural logs) of baseline and follow-up levels of TUNEL between DTN and DT treatment arms.

  • Change in BCL2 [ Time Frame: Baseline to up to 1 week ] [ Designated as safety issue: No ]
    Will be primarily descriptive.

  • Change in Ki67 [ Time Frame: Baseline to up to 1 week ] [ Designated as safety issue: No ]
    Will be primarily descriptive.

  • Change in phosphatase and tensin homolog (PTEN) status [ Time Frame: Baseline to up to 1 week ] [ Designated as safety issue: No ]
    Will be primarily descriptive.

  • Fold changes in BRAF-mutation assay [ Time Frame: Baseline to up to 4 weeks after last study treatment ] [ Designated as safety issue: No ]
    Fold-changes in assay response will be calculated (post/pre). Fold changes in the assay will be compared across RECIST responses using the Kruskal-Wallis test. In addition, for assay-based response or progression, the proportions of patients with CR/partial response (PR), stable disease (SD), or progressive disease (PD) will be presented with exact 90% confidence intervals. Assay performance data will be compared with response. The proportions will be summarized and compared using exact confidence intervals. Behavior of the blood assay will be summarized graphically.

  • Fold changes in tumor burden [ Time Frame: Baseline to up to 4 weeks after last study treatment ] [ Designated as safety issue: No ]
    Assay fold changes will be compared with fold changes in tumor burden (post/pre). The relationship will be summarized graphically and using the Spearman rank correlation. Differences in the behavior of the assay will be explored using a general linear model of log(fold-change) with study, baseline tumor burden, and log(fold-change tumor burden) as predictors.

  • Pharmacokinetic parameters, including maximal plasma or serum concentration (Cmax), area under the curve to the last collection point (AUClast), area under the curve for dose interval (AUC0-t), and time of maximal concentration (Tmax) [ Time Frame: Pre-treatment, 1, 2, 4, 6, 8, and 24 hours post-treatment on days 1, 2, and 15 of course 1 and day 1 of courses 2, 4, 8, and 12 ] [ Designated as safety issue: No ]
    Descriptive statistics including mean, standard deviation, coefficient of variation, geometric mean, median, minimum and maximum will be computed for each pharmacokinetic variable; descriptive statistics for natural-log transformed pharmacokinetic variables will also be provided.


Estimated Enrollment: 70
Study Start Date: October 2013
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (dabrafenib, trametinib)
Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: dabrafenib
Given PO
Other Names:
  • BRAF inhibitor GSK2118436
  • GSK-2118436A
  • GSK2118436
  • Tafinlar
Drug: trametinib
Given PO
Other Names:
  • GSK1120212
  • JTP-74057
  • Mekinist
Biological: navitoclax
Given PO
Other Names:
  • ABT-263
  • BcI-2 family protein inhibitor ABT-263
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II (dabrafenib, trametinib, and navitoclax)
Patients receive navitoclax PO QD days -7 to -1 of course 1 only. Patients also receive dabrafenib PO BID, trametinib PO QD, and navitoclax PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: dabrafenib
Given PO
Other Names:
  • BRAF inhibitor GSK2118436
  • GSK-2118436A
  • GSK2118436
  • Tafinlar
Drug: trametinib
Given PO
Other Names:
  • GSK1120212
  • JTP-74057
  • Mekinist
Biological: navitoclax
Given PO
Other Names:
  • ABT-263
  • BcI-2 family protein inhibitor ABT-263
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD), toxicity, and safety profile of navitoclax when given in combination with dabrafenib and trametinib in patients with v-raf murine sarcoma viral oncogene homolog B (BRAF)-mutant solid tumors. (Phase I) II. To estimate the complete response (CR) rate in patients with BRAF-mutant melanoma treated with dabrafenib, trametinib, and navitoclax as compared to the historical control. (Phase II) III. To compare the maximal tumor regression in patients with BRAF-mutant melanoma treated with dabrafenib, trametinib versus dabrafenib, trametinib, and navitoclax. (Phase II)

SECONDARY OBJECTIVES:

I. To describe pharmacodynamics effects of treatment with dabrafenib, trametinib, and navitoclax on both serial tumor biopsies and serial blood draws in a small subset of patients treated with BRAF-mutant melanoma. (Phase I) II. To describe the pharmacokinetics of treatment with dabrafenib, trametinib, and navitoclax. (Phase I) III. To compare the progression-free survival (PFS), overall survival (OS), and overall response rate (ORR) in patients with BRAF-mutant melanoma treated with dabrafenib, trametinib, versus dabrafenib, trametinib, and navitoclax. (Phase II) IV. To compare the degree of apoptosis induced in on-treatment biopsies of patients with BRAF-mutant melanoma treated with dabrafenib, trametinib versus dabrafenib, trametinib, and navitoclax. (Phase II) V. To explore other pharmacodynamic effects in on-treatment biopsies of patients with BRAF-mutant melanoma treated with either dabrafenib, trametinib versus dabrafenib, trametinib, and navitoclax including cell proliferation (Ki-67), proteomics (reverse-phase protein microarrays [RPPA]), and B-cell chronic lymphocytic leukemia (CLL)/lymphoma 2 (BCL-2) family gene expression analysis. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of dabrafenib, trametinib, and navitoclax followed by a randomized phase II study.

PHASE I: Patients receive navitoclax orally (PO) once daily (QD) on days -7 to -1 of course 1 only. Patients also receive dabrafenib PO twice daily (BID), trametinib PO QD, and navitoclax PO QD days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive navitoclax PO QD days -7 to -1 of course 1 only. Patients also receive dabrafenib PO BID, trametinib PO QD, and navitoclax PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After the completion of study treatment, patients are followed up for 28 days.

  Eligibility

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

Inclusion Criteria:

  • For Phase I: patients must have histologically confirmed, BRAF-mutant (V600E/K) malignancy (molecularly confirmed using validated, commercially available assay performed in a Clinical Laboratory Improvement Amendments [CLIA]-approved laboratory) that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective

    • If test at CLIA-certified lab used a non-Food and Drug Administration (FDA) approved method, information about the assay must be provided; (FDA approved tests for BRAF V600 mutations in melanoma include: THxID BRAF Detection Kit and Cobas 4800 BRAF V600 mutation test)
  • For Phase II: patients must have histologically confirmed, BRAF-mutant (V600E/K) melanoma (molecularly confirmed using validated, commercially available assay performed in a CLIA-approved laboratory) that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective

    • If test at CLIA-certified lab used a non-FDA approved method, information about the assay must be provided; (FDA approved tests for BRAF V600 mutations in melanoma include: THxID BRAF detection kit and Cobas 4800 BRAF V600 mutation test)
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
  • Prior therapy is allowed:

    • Phase I: for patients enrolled in the phase I portion of the study, patients may have received any number of prior lines of therapy including treatment with a BRAF and/or mitogen-activated protein kinase kinase (MEK) inhibitor; prior navitoclax use will not be allowed;
    • Phase II: for patients enrolled in the phase II portion of the study, patients may have received prior immunotherapy (including high-dose interleukin [IL]-2, ipilimumab, nivolumab, and other anti-programmed cell death 1 [PD1]/cluster of differentiation (CD)274 molecule [PDL1] antibodies) or chemotherapy, however prior navitoclax, BRAF inhibitor and/or MEK inhibitor therapy will not be allowed
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
  • Life expectancy of greater than 3 months
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 100 x 10^9/L
  • Hemoglobin >= 9 g/dl (patients may be transfused to this level)
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 1.5 x institutional upper limit of normal OR > 1.5 x institutional upper limit of normal allowed if direct bilirubin is within normal range
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
  • Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) < 1.3 x upper limit of normal (ULN)
  • Serum creatinine =< 1.5 mg/dL OR creatinine clearance >= 50 mL/min/1.73 m^2
  • Left ventricular ejection fraction >= institutional lower limit of normal (LLN) by echocardiogram (ECHO)
  • Patients must have a corrected QT (QTc) interval of less than 480 msec
  • Women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control, or abstinence; hormonal contraception is not allowed) prior to study entry, for the duration of study participation, and for 4 months after completion of study drug administration; should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately
  • Therapeutic level dosing of warfarin can be used with close monitoring of PT/INR by the site; exposure may be decreased due to enzyme induction when on treatment, thus warfarin dosing may need to be adjusted based upon PT/INR; consequently, when discontinuing dabrafenib, warfarin exposure may be increased and thus close monitoring via PT/INR and warfarin dose adjustments must be made as clinically appropriate; prophylactic low dose warfarin may be given to maintain central catheter patency
  • 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
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients who have had immunotherapy, chemotherapy or radiotherapy within 14 days prior to the first dose of navitoclax, or prior systemic anti-cancer therapy (chemotherapy with delayed toxicity, extensive radiation therapy, immunotherapy, biologic therapy, or vaccine therapy) within the last 3 weeks prior to first dose of dabrafenib and/or trametinib; chemotherapy regimens without delayed toxicity within the last 2 weeks preceding the first dose of study treatment; biologics will not be allowed within 30 days prior to, or during, navitoclax administration
  • Patients must not have received prior navitoclax; in the phase II portion of the study, prior BRAF inhibitor and/or MEK inhibitor will be prohibited
  • Patients who are receiving any other investigational agents have received any other investigational drugs within 28 days (or five half-lives, whichever is shorter; with a minimum of 14 days from the last dose) preceding the first dose of study treatment and during the study
  • Patients must have no clinical evidence of leptomeningeal or brain metastasis causing spinal cord compression that are symptomatic or untreated or not stable for >= 3 months (must be documented by imaging) or requiring corticosteroids; subjects on a stable dose of corticosteroids > 1 month or who have been off of corticosteroids for at least 2 weeks can be enrolled with approval of the Cancer Therapy Evaluation Program (CTEP) medical monitor; subjects must also be off of enzyme-inducing anticonvulsants for > 4 weeks
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to navitoclax, dabrafenib, or trametinib, or excipients or to dimethyl sulfoxide (DMSO)
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active serious infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled diabetes, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with the study drugs
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
  • History of another malignancy other than the study indication under this trial within 5 years of study enrollment; exception: patients with history of RAS mutation-positive tumors are not eligible regardless of interval from the current study; prospective retrovirus-associated deoxyribonucleic acid (DNA) sequence (RAS) testing is not required; however, if the results of previous RAS testing are known, they must be used in assessing eligibility
  • History of interstitial lung disease or pneumonitis
  • History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR):

    • History of RVO or CSR, or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes)
    • Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or CSR such as evidence of new optic disc cupping, evidence of new visual field defects, and intraocular pressure > 21 mmHg
  • History or evidence of cardiovascular risk including any of the following:

    • A QT interval corrected for heart rate using the Bazett's formula QTcB >= 480 msec
    • History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to randomization are eligible)
    • History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization
    • History or evidence of current >= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system
    • Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy
    • Abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study
  • History of hepatitis B virus (HBV), or hepatitis C virus (HCV) infection (patients with chronic or cleared HBV and HCV infection are eligible)
  • Subject has an underlying condition predisposing them to bleeding or currently exhibits signs of clinically significant bleeding
  • Subject has a recent history of non-chemotherapy-induced thrombocytopenic-associated bleeding within 1 year prior to the first dose of study drug
  • A history of glucose-6-phosphate dehydrogenase (G6PD) deficiency
  • Unresolved toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI CTCAE v4.0) grade 2 or higher from previous anti-cancer therapy, except alopecia, at the time of randomization
  • The following concomitant medications are not allowed during navitoclax administration: clopidogrel, ibuprofen, tirofiban, warfarin, and other anticoagulants, drugs, or herbal supplements that affect platelet function are excluded, with the exception of low-dose anticoagulation medications (such as heparin) that are used to maintain the patency of a central intravenous catheter; aspirin will not be allowed within 7 days prior to the first dose of navitoclax or during navitoclax administration; however, subjects who have previously received aspirin therapy for thrombosis prevention may resume a low dose (i.e., maximum 100 mg QD) of aspirin if platelet counts are stable (>= 50,000/mm^3) through 6 weeks of navitoclax administration; all decisions regarding treatment with aspirin therapy will be determined by the investigator in conjunction with the medical monitor
  • Current use of a prohibited medication; the following medications or non-drug therapies are prohibited:

    • Other anti-cancer therapy while on study treatment; (note: megestrol [Megace] if used as an appetite stimulant is allowed)
    • Concurrent treatment with bisphosphonates is permitted; however, treatment must be initiated prior to the first dose of study therapy; prophylactic use of bisphosphonates in patients without bone disease is not permitted, except for the treatment of osteoporosis
    • Concurrent use of all herbal supplements is prohibited during the study (including, but not limited to, St. John's wort, kava, ephedra [ma huang], ginkgo biloba, dehydroepiandrosterone [DHEA], yohimbe, saw palmetto, or ginseng)
    • Anticoagulants or antiplatelet agents except for low-dose, 81 mg aspirin
  • Caution should be exercised when dosing navitoclax concurrently with cytochrome P450, family 2, subfamily C, peptide 8 (CYP2C8) and cytochrome P450, family 2, subfamily C, peptide 9 (CYP2C9) substrates; common CYP2C8 substrates include paclitaxel, statins, and glitazones, whereas CYP2C9 substrates include phenytoin; when possible, investigators should switch to alternative medications or monitor the patients closely; cytochrome P450, family 3, subfamily A (CYP3A) inhibitors such as ketoconazole and clarithromycin are not allowed 7 days prior to the first dose of navitoclax or during navitoclax administration
  • Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A or CYP2C8 are ineligible; current use of, or intended ongoing treatment with: herbal remedies (e.g., St. John's wort), or strong inhibitors or inducers of P-glycoprotein (Pgp) or breast cancer resistance protein 1 (Bcrp1) should also be excluded; below are a few examples of the agents:

    • Strong inducers of CYP3A or CYP2C8:

      • Antibiotics: rifamycin class agents (e.g., rifampin, rifabutin, rifapentine)
      • Anticonvulsants: carbamazepine, oxcarbazepine, phenobarbital, phenytoin, s-mephenytoin
      • Miscellaneous: bosentan, St. John's wort
    • Strong inhibitors of CYP3A or CYP2C8

      • Antibiotics: clarithromycin, telithromycin, troleandomycin
      • Antidepressants: nefazodone
      • Antifungals: itraconazole, ketoconazole, posaconazole, voriconazole
      • Hyperlipidemia: gemfibrozil
      • Antiretroviral: ritonavir, saquinavir, atazanavir
      • Miscellaneous: conivaptan
  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: NCT01989585

Locations
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Jason J. Luke    617-632-4715    Jason_Luke@dfci.harvard.edu   
Principal Investigator: Jason J. Luke         
Massachusetts General Hospital Cancer Center Recruiting
Boston, Massachusetts, United States, 02114
Contact: Ryan J. Sullivan    617-724-4000    rsullivan7@partners.org   
Principal Investigator: Ryan J. Sullivan         
United States, New Jersey
Rutgers Cancer Institute of New Jersey Recruiting
New Brunswick, New Jersey, United States, 08903
Contact: Janice M. Mehnert    732-235-6031    mehnerja@cinj.rutgers.edu   
Principal Investigator: Janice M. Mehnert         
United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Michael A. Davies    713-792-3454    mdavies@mdanderson.org   
Principal Investigator: Michael A. Davies         
Sponsors and Collaborators
Investigators
Principal Investigator: Ryan Sullivan Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01989585     History of Changes
Obsolete Identifiers: NCT01970956
Other Study ID Numbers: NCI-2013-02103, NCI-2013-02103, 13-424, 9466, UM1CA186716, U01CA132194, P30CA006516, UM1CA186709, U01CA062490
Study First Received: November 18, 2013
Last Updated: September 16, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on September 22, 2014