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Metastatic Malignant Solid NeoplasmPhase 1/2NCT02079740

Trametinib and Navitoclax in Treating Patients With Advanced or Metastatic Solid Tumors

A Phase 1/2 study testing Biopsy Procedure, Biospecimen Collection and Computed Tomography in people with Metastatic Malignant Solid Neoplasm and Refractory Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 2 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This phase Ib/II trial studies the side effects and best dose of trametinib and navitoclax and how well they work in treating patients with solid tumors that have spread to other places in the body (advanced or metastatic). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biopsy Procedure, Biospecimen Collection and Computed Tomography
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
96 participants
Where
2 sitesUnited States
Study dates
26 Mar 2014to 9 Mar 2027
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have histologically- or cytologically-confirmed diagnosis of KRAS or NRAS mutation-positive malignancy that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective; patients must have activating mutations affecting codons 12, 13, 61, or 146 as determined in a Clinical Laboratory Improvement Amendments (CLIA)-certified lab to be eligible for this study
  • Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST), 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 by chest x-ray or as >= 10 mm with CT scan, MRI, or calipers by clinical exam
  • Participants must have received at least one line of prior systemic chemotherapy and must have experienced documented radiographic progression or intolerance on this therapy
  • Paired pre-treatment and post-treatment biopsies are required for all patients on Part 1 and first 15 patients in Part 2; participants must have available archival tumor tissue (at least 20 unstained slides); if archival tissue is not available or is found not to contain tumor tissue, a fresh biopsy is required; if a patient is having a tumor biopsy, less than 20 unstained slides are acceptable with approval of the principal investigator (PI); biopsies will only be performed in a given patient if they are not deemed to involve unacceptable risk based on the sites of disease and other concurrent medical conditions
  • Age >= 18 years
  • Because no dosing or adverse event data are currently available on the use of trametinib in combination with navitoclax in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
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  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1
  • Life expectancy of greater than 3 months
  • Able to swallow and retain orally-administered 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
  • All prior treatment-related toxicities must be Common Terminology Criteria for Adverse Events version 4 (CTCAE v 4) grade =< 1 (except alopecia) at the time of enrollment; this requirement to return to =< grade 1 does not apply to immune checkpoint inhibitor related endocrinopathies (e.g. thyroiditis, hypophysitis, etc.) that necessitate hormone replacement therapy including, but not limited to levothyroxine, cortisol, and testosterone; CTCAE v5.0 will be utilized beginning April 1, 2018
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count (ANC) >= 1,200/mcL (subjects may be treated with hematopoietic growth factors to achieve or maintain this level)
  • Hemoglobin >= 9 g/dL
  • Platelets >= 100 x 10^9/L
  • Albumin >= 2.5 g/dL
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (patients with Gilbert's syndrome may have serum bilirubin > 1.5 x ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x institutional ULN
  • Serum creatinine =< 1.5 mg/dL OR calculated creatinine clearance (Cockcroft-Gault formula) >= 50 mL/min OR 24-hour urine creatinine clearance >= 50 mL/min
  • Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.2 x institutional ULN
  • Left ventricular ejection fraction >= institutional lower limit of normal (LLN) by echocardiogram (ECHO) or multi gated acquisition scan (MUGA)
  • The effects of trametinib and navitoclax on the developing human fetus are unknown. For this reason, women of child-bearing potential and men with a female partner of child bearing potential must agree to use adequate contraception using one of the methods listed below prior to study entry, for the duration of study participation, and up to 4 months following completion of therapy
  • Total abstinence from sexual intercourse (minimum one complete menstrual cycle prior to study drug administration)
  • Vasectomized male subject or vasectomized partner of female subjects
  • Hormonal contraceptives (oral, parenteral, transdermal or vaginal ring) for at least 3 months prior to study drug administration; if the subject is currently using a hormonal contraceptive, she should also use a barrier method during this study and for 1 month after study completion
  • Intrauterine device (IUD)
  • Double-barrier method: male condom plus diaphragm or vaginal cap with spermicide (contraceptive sponge, jellies or creams)
  • Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception; additionally, male subjects (including those who are vasectomized) whose partners are pregnant or might be pregnant must agree to use condoms for the duration of the study and for 4 months following completion of therapy
  • Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to initiation of treatment; women will be considered not of childbearing potential if they are surgically sterile (bilateral oophorectomy or hysterectomy) and/or post-menopausal (amenorrheic for at least 12 months); should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; the potential hazard to the fetus should be explained to the patient and partner (as applicable)
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • History of another malignancy; exception: patients who have been disease-free for 3 years, or patients with a history of completely resected non-melanoma skin cancer or any carcinoma in situ and/or patients with indolent second malignancies, are eligible; consult the Cancer Therapy Evaluation Program (CTEP) medical monitor if unsure whether second malignancies meet the requirements specified above
  • History of interstitial lung disease or pneumonitis
  • Any major surgery, extensive radiotherapy (> 15 days of treatment), chemotherapy with delayed toxicity, biologic therapy, or immunotherapy within 21 days prior to first dose of study treatment and/or daily or weekly chemotherapy without the potential for delayed toxicity within 14 days prior to first dose of study treatment
  • Use of 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 drug(s) and during the study
  • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; exception: patients with brain metastases will be allowed on study if they have clinically controlled neurologic symptoms, defined as surgical excision and/or radiation therapy followed by 21 days of stable neurologic function and no evidence of central nervous system (CNS) disease progression as determined by CT or MRI within 21 days prior to the first dose of study drug
  • Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trametinib, or excipients or to dimethyl sulfoxide (DMSO), or to compounds of similar chemical or biologic composition to navitoclax
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  • 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
  • Because the composition, pharmacokinetics (PK), and metabolism of many herbal supplements are unknown, the 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)
  • Due to the expected dose-limiting toxicity of thrombocytopenia, the following concomitant medications are not allowed during navitoclax administration: Warfarin, clopidogrel (plavix), ibuprofen, tirofiban (aggrastat), 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
  • Preclinical studies indicate that navitoclax is metabolized by CYP3A4, is a moderate inhibitor of CYP2C8, and is a strong inhibitor of CYP2C9; therefore, caution should be exercised when dosing navitoclax concurrently with CYP2C8 and CYP2C9 substrates; common CYP2C8 substrates include paclitaxel, statins, and glitazones, whereas CYP2C9 substrates include phenytoin and warfarin; when possible, investigators should switch to alternative medications or monitor the patients closely (particularly in the case of medications that have a narrow therapeutic window such as warfarin; use of warfarin is specifically prohibited while on study); CYP3A inhibitors such as ketoconazole and clarithromycin are not allowed 7 days prior to the first dose of navitoclax or during navitoclax administration
  • Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list; medical reference texts such as the Physicians' Desk Reference may also provide this information; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
  • Patient instructions and information of possible drug interactions will be given to all patients upon enrollment in this study
  • History or current evidence/risk of retinal vein occlusion (RVO)
  • History or evidence of cardiovascular risk including any of the following:
  • Left ventricle ejection fraction (LVEF) < LLN
  • 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 enrollment 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
  • Known cardiac metastases
  • Patients with intra-cardiac defibrillators
  • Known hepatitis B virus (HBV), or hepatitis C virus (HCV) infection (patients with chronic or cleared HBV and HCV infection are eligible); patients with human immunodeficiency virus (HIV) are not eligible if on anti-retroviral medications
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • 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
  • Subject has a significant history of cardiovascular disease (e.g., myocardial infarction [MI], thrombotic or thromboembolic event in the last 6 months)
  • Pregnant women or nursing mothers; animal reproductive studies have not been conducted with trametinib or navitoclax; therefore, the study drug must not be administered to pregnant women or nursing mothers

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: An Open Label, Two-Part, Phase Ib/II Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of the MEK Inhibitor Trametinib and the BCL2-Family Inhibitor Navitoclax (ABT-263) in Combination in Subjects With KRAS or NRAS Mutation-Positive Advanced Solid Tumors

This phase Ib/II trial studies the side effects and best dose of trametinib and navitoclax and how well they work in treating patients with solid tumors that have spread to other places in the body (advanced or metastatic). Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Navitoclax inhibits members of the BCL2 family of proteins that are believed to play key roles in promoting the survival of cancer cells. It may stop the growth of cancer cells by blocking Bcl-2, Bcl-XL, and Bcl-w, proteins needed for cancer cell survival. Giving trametinib and navitoclax may help stop the growth of tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the dose-limiting toxicities of trametinib in combination with navitoclax, and the maximal doses at which both drugs can be safely administered together. (Phase Ib) II. To determine the response rate of the combination of trametinib and navitoclax in subjects with KRAS or NRAS mutation-positive advanced or metastatic solid tumors in disease-specific expansion cohorts. (Phase II) III. To confirm the safety and tolerability of trametinib and navitoclax in combination at the recommended phase 2 dose (RP2D) determined in the Phase 1b portion. (Phase II)

SECONDARY OBJECTIVES:

  1. To determine the pharmacokinetics of both drugs administered together. (Phase Ib) II. To assess for evidence of response to therapy. (Phase Ib) III. To evaluate the pharmacodynamic response to therapy in tumor biopsies. (Phase Ib) IV. To evaluate the pharmacodynamic response to therapy in tumor biopsies (first 15 patients enrolled overall). (Phase II)

OUTLINE: This is a phase Ib, dose-escalation study followed by a phase II study.

Patients receive trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. If unacceptable toxicity is observed, patients may receive trametinib PO QD on days 1-14. Patients also undergo computed tomography (CT), positron emission tomography (PET)/CT, or magnetic resonance imaging (MRI) every 8 weeks following cycle 1 day 1, biopsy on day 15 or 22 of cycle 1, and collection of blood samples on day 1 of cycles 2, 4, 8, and 12.

After completion of study treatment, patients are followed up for 30 days.

Being tested
Biopsy Procedure, Biospecimen Collection, Computed Tomography, Magnetic Resonance Imaging, Navitoclax
Medical subject headings
Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biopsy ProcedureProcedure or surgery

    Also called Biopsy, BIOPSY_TYPE, Bx

    Undergo biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo collection of blood samples

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo conventional CT or PET/CT

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • NavitoclaxBiological

    Also called A-855071.0, ABT-263, BcI-2 Family Protein Inhibitor ABT-263

    Given PO

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET/CT

  • TrametinibDrug

    Also called GSK 1120212, GSK 212, GSK-1120212, GSK-212

    Given PO

Study groups in NCT02079740
Study groupRoleWhat they receive
Treatment (trametinib, navitoclax)ExperimentalPatients receive trametinib PO QD and navitoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. If unacceptable toxicity is observed, patients may receive trametinib PO QD on days 1-14.
Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Biological: Navitoclax; Procedure: Positron Emission Tomography; Drug: Trametinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. (Phase 1b) Maximal Tolerated Dose of Trametinib and Navitoclax

    Dose escalation uses a 3+3 enrollment design per dose level. The occurrence of 1 dose limiting toxicity (DLT) will prompt expansion of a given dose level to 6 participants. The occurrence of 2 DLTs in a given dose level will indicate that the maximal tolerated dose (MTD) has been exceeded, and expansion of the prior dose level to 6 participants will occur, if not already performed. The recommended phase 2 dose (RP2D) will be the highest dose level at which no more than 1 out of 6 participants experiences a DLT. Dose escalation will proceed until the MTD/RP2D have been determined.

    Measured: Within the first 42 days of treatment

  2. (Phase 1b) Dose-Limiting Toxicities of Trametinib and Navitoclox

    Dose-limiting toxicity (DLT) are adverse events (AEs) that are serious enough to prevent an increase in dose level of that treatment. Grading based on Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. CTCAE version 5.0 will be utilized beginning April 1, 2018.

    Measured: Within the first 42 days of treatment

  3. (Phase 2) Response Rate

    Response rate is defined as the number of participants who achieve complete response (CR) or partial response (PR), according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1:

    • CR = Disappearance of target lesion(s). Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm
    • PR = At least a 30% decrease in the sum of the longest diameter(s) of target lesion(s)

    Participants are considered evaluable for response if they had measurable disease present at baseline, received at least one cycle of therapy, and had their disease re-evaluated at least once after initiating therapy.

    Measured: Up to 6 months

  4. (Phase 2) Progression-free Survival

    Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progressive disease (PD) or death, whichever occurs first.

    PD is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 as at least a 20% increase in the (sum of the) longest diameter(s) of target lesion(s), and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

    Measured: Up to 31 months

  5. (Phase 2) Treatment Emergent Adverse Events

    Treatment emergent adverse events (TEAEs) are undesirable events not present prior to study treatment, or an already present event that worsens either in intensity or frequency while on treatment. TEAEs are assessed as grade 3 or higher according to Common Terminology Criteria for Adverse Events (CTCAE) criteria version 4.0. CTCAE criteria version 5.0 will be utilized beginning April 1, 2018. TEAEs are also assessed as possibly, probably, or definitely related to study treatment.

    Measured: up to 29 months on treatment

Secondary outcomes (6)

  1. (Phase 1b) Pharmacokinetic Parameter Cmax for Trametinib and Navitoclax When Administered in Combination

    Pharmacokinetic blood draw samples collected for the following parameter and reported as mean values per day: maximum observed plasma drug concentration (Cmax).

    Schedule A:

    • C1 D7 = pre-nav (0h) then 2h, 4h, 6h, 8h
    • C1 D8 = pre-tram (-1h = 23h post-nav)
    • C1 D21 = pre-tram (-1h); pre-nav (0h); then 2h, 4h, 6h, 8h post-nav
    • C1 D22 = pre-tram (-1h = 23h post-nav)
    • D1 of Cycle 2,4,8,12 (single trough) = pre-tram (-1h)

    Schedule B:

    • C1 D7, D14 = pre-tram (-1h); pre-nav (0h); then 2h, 4h, 6h, 8h post-nav
    • C1 D8, D15 = pre-tram (-1h = 23h post-nav)
    • D1 of Cycle 2,4,8,12 (single trough) = pre-tram (-1h)

    Schedule C:

    • C1 D7, D14 = pre-navitoclax (0h) then 2h, 4h, 6h, 8h
    • C1 D8, D15 = pre-trametinib (-1h = 23h post-navitoclax)
    • D1 of Cycle 2,4,8,12 (single trough) = pre-nav (0h)

    Measured: Cycle 1 day 7 and day 21

  2. (Phase 1b) Pharmacokinetic Parameter AUC for Trametinib and Navitoclax When Administered in Combination

    Pharmacokinetic blood draw samples collected for the following parameter and reported as mean values per day: area under the concentration time curve from zero (pre-dose) to 24 hours (AUC 0-24).

    Schedule A:

    • C1 D7 = pre-nav (0h) then 2h, 4h, 6h, 8h
    • C1 D8 = pre-tram (-1h = 23h post-nav)
    • C1 D21 = pre-tram (-1h); pre-nav (0h); then 2h, 4h, 6h, 8h post-nav
    • C1 D22 = pre-tram (-1h = 23h post-nav)
    • D1 of Cycle 2,4,8,12 (single trough) = pre-tram (-1h)

    Schedule B:

    • C1 D7, D14 = pre-tram (-1h); pre-nav (0h); then 2h, 4h, 6h, 8h post-nav
    • C1 D8, D15 = pre-tram (-1h = 23h post-nav)
    • D1 of Cycle 2,4,8,12 (single trough) = pre-tram (-1h)

    Schedule C:

    • C1 D7, D14 = pre-navitoclax (0h) then 2h, 4h, 6h, 8h
    • C1 D8, D15 = pre-trametinib (-1h = 23h post-navitoclax)
    • D1 of Cycle 2,4,8,12 (single trough) = pre-nav (0h)

    Measured: Cycle 1 day 7 and day 21

  3. (Phase 1b) Pharmacokinetic Parameter C0 for Trametinib and Navitoclax When Administered in Combination

    Pharmacokinetic blood draw samples collected for the following parameter and reported as mean values per day: trough plasma drug concentration (C0).

    Schedule A:

    • C1 D7 = pre-nav (0h) then 2h, 4h, 6h, 8h
    • C1 D8 = pre-tram (-1h = 23h post-nav)
    • C1 D21 = pre-tram (-1h); pre-nav (0h); then 2h, 4h, 6h, 8h post-nav
    • C1 D22 = pre-tram (-1h = 23h post-nav)
    • D1 of Cycle 2,4,8,12 (single trough) = pre-tram (-1h)

    Schedule B:

    • C1 D7, D14 = pre-tram (-1h); pre-nav (0h); then 2h, 4h, 6h, 8h post-nav
    • C1 D8, D15 = pre-tram (-1h = 23h post-nav)
    • D1 of Cycle 2,4,8,12 (single trough) = pre-tram (-1h)

    Schedule C:

    • C1 D7, D14 = pre-navitoclax (0h) then 2h, 4h, 6h, 8h
    • C1 D8, D15 = pre-trametinib (-1h = 23h post-navitoclax)
    • D1 of Cycle 2,4,8,12 (single trough) = pre-nav (0h)

    Measured: Cycle 1 day 7 and day 21

  4. (Phase 1b) Response Rate

    Response rate is defined as the number of participants who achieve complete response (CR) or partial response (PR), according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1:

    • CR = Disappearance of target lesion(s). Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm
    • PR = At least a 30% decrease in the sum of the longest diameter(s) of target lesion(s)

    Participants are considered evaluable for response if they had measurable disease present at baseline, received at least one cycle of therapy, and had their disease re-evaluated at least once after initiating therapy.

    Measured: Up to 4 months

  5. (Phase 2) Pharmacokinetic Parameters for Trametinib and Navitoclax When Administered in Combination at Recommended Phase 2 Dose

    Pharmacokinetic (PK) blood draw samples collected for the following parameters:

    • Maximum observed plasma drug concentration (Cmax)
    • Area under the concentration time curve from zero (pre-dose) to 24 hours (AUC 0-24)
    • Pre-dose (trough) drug concentration at the end of the dosing interval (C0)
    • Half-life (t1/2)

    Recommended phase 2 dose (RP2D) schedule:

    • Day 1 of cycles 2, 4, 8, 12 = pre-trametinib (-1h)

    Measured: Day 1 of cycles 2, 4, 8, and 12

  6. (Phase 1b and 2) Percent Change in Levels of Proteins/Messenger Ribonucleic Acids Implicated in Mitogen-activated Protein Kinase Signaling

    Paired pre-treatment and on treatment tumor biopsies will be obtained to assess the pharmacodynamic response to therapy (e.g., change in levels of proteins/mRNAs implicated in MAPK signaling). Results will be reported as a mean percent (%) change in MAPK transcripts day 15 vs day 0.

    Pre-treatment tumor tissue for analysis will be obtained either from archival tissue remaining from a participant's prior surgery, diagnostic biopsy, or other procedure performed during routine clinical care. Alternatively, study-related pre-treatment biopsies will be obtained between days -21 and -1 of treatment if necessary.

    On-treatment biopsies will be obtained after ~2 weeks of Cycle 1 combination dosing:

    • Phase 1b Schedule A = Day 22 +/- 7 days
    • Phase 1b Schedule B or C = Day 15 +/- 7 days
    • Phase 2 RP2D = Day 15 +/- 7 days

    Measured: up to 50 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Mar 2014 (estimated)
  2. Study start26 Mar 2014
  3. Primary completion1 Dec 2022
  4. Study completion9 Mar 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
96 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02079740
Sponsor's protocol ID
NCI-2014-00461
Other IDs
NCI-2014-00461, 13-505, 9525, 9525, P30CA006516, P50CA127003, U01CA062490, UM1CA186709
Status last verified
Sep 2026
First submitted
4 Mar 2014
Last updated
11 Sep 2026
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Biopsy Procedure, Biospecimen Collection and Computed Tomography in people with Metastatic Malignant Solid Neoplasm and Refractory Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 11 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

(Phase 1b) Maximal Tolerated Dose of Trametinib and Navitoclax (time frame: Within the first 42 days of treatment). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02079740.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2026.

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