Clinical Trials /

Trametinib in Combination With Paclitaxel in the Treatment of Anaplastic Thyroid Cancer

NCT03085056

Description:

The purpose of this study is to test the safety and tolerability of this treatment combination of paclitaxel and trametinib. Additionally, this study aims to to find out what effects the combination of paclitaxel and trametinib has on the shrinkage and growth of anaplastic thyroid cancer.

Related Conditions:
  • Thyroid Gland Undifferentiated (Anaplastic) Carcinoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Trametinib in Combination With Paclitaxel in the Treatment of Anaplastic Thyroid Cancer
  • Official Title: A Pilot Study of Trametinib in Combination With Paclitaxel in the Treatment of Anaplastic Thyroid Cancer

Clinical Trial IDs

  • ORG STUDY ID: 15-055
  • NCT ID: NCT03085056

Conditions

  • Anaplastic Thyroid Cancer

Interventions

DrugSynonymsArms
TrametinibTrametinib in Combination With Paclitaxel
PaclitaxelTrametinib in Combination With Paclitaxel

Purpose

The purpose of this study is to test the safety and tolerability of this treatment combination of paclitaxel and trametinib. Additionally, this study aims to to find out what effects the combination of paclitaxel and trametinib has on the shrinkage and growth of anaplastic thyroid cancer.

Trial Arms

NameTypeDescriptionInterventions
Trametinib in Combination With PaclitaxelExperimentalPatients will receive paclitaxel 80mg/m^2 weekly for 3 out of 4 weeks, which is a standard regimen in the treatment of anaplastic thyroid cancer, in combination with trametinib 2mg daily during each 4 week cycle.
  • Trametinib
  • Paclitaxel

Eligibility Criteria

        Inclusion Criteria:

          -  Pathologically (histologically or cytologically) proven diagnosis of anaplastic
             thyroid cancer (a diagnosis that is noted to be consistent with anaplastic thyroid
             cancer is acceptable).

          -  Metastatic disease or local-regional disease that is considered not resectable for
             cure.

          -  Patients must have measurable disease per RECIST v1.1 criteria, 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 CT scan, MRI, or
             calipers by clinical exam

          -  Age ≥18 years

          -  ECOG performance status ≤2 (Karnofsky ≥60)

          -  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

          -  No CTCAE v4 grade >2 neuropathy

          -  Patients must have normal organ and marrow function as defined below:

               -  Absolute neutrophil count (ANC) ≥1.5x10^9/L

               -  Hemoglobin ≥9 g/dL

               -  Platelets ≥100x10^9/L

               -  Serum bilirubin ≤1.5x institutional upper limit of normal (ULN) (Unless
                  Gilbert's Disease in which case total bilirubin ≤3x institutional ULN)

               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5x
                  institutional ULN (≤5x institutional ULN if there is liver metastasis)

               -  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

               -  Left ventricular ejection fraction ≥ institutional lower limit of normal (LLN)
                  by ECHO or MUGA

          -  Negative pregnancy test (serum or urine) within 14 days of registration in women of
             child-bearing potential. Women of child-bearing potential and men must agree to use
             adequate contraception (hormonal or barrier method of birth control; abstinence)
             prior to study entry and for the duration of study participation. Men treated or
             enrolled on this protocol must also agree to use adequate contraception prior to the
             study, for the duration of study participation, and 4 months after completion of
             trametinib administration

          -  Ability to understand and the willingness to sign a written informed consent
             document.

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 21 days of enrollment.

          -  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
             trametinib and during the study

          -  Symptomatic or untreated brain metastases, leptomeningeal disease, or spinal cord
             compression

          -  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)

               -  Visible retinal pathology as assessed by ophthalmic exam that is considered a
                  high risk factor for RVO or CSR such as evidence of new optic disc cupping,
                  evidence of new visual field defects, and intraocular pressure >21 mm Hg

          -  History or evidence of cardiovascular risk including any of the following:

               -  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 >150
                  mmHg and/or diastolic >90 mmHg which cannot be controlled by anti-hypertensive
                  therapy

               -  Known cardiac metastases

          -  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) HIV-positive patients on combination antiretroviral
             therapy are ineligible because of the potential for pharmacokinetic interactions with
             trametinib. In addition, these patients are at increased risk of lethal infections
             when treated with marrow-suppressive therapy. Appropriate studies will be undertaken
             in patients receiving combination antiretroviral therapy when indicated

          -  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

          -  Any condition that may impair the ability to absorb oral medications/investigational
             product including: prior surgical procedures affecting absorption including, but not
             limited to major resection of stomach or small bowel; active peptic ulcer disease;
             and malabsorption syndrome

          -  Any major surgery within 21 days prior to enrollment.

          -  Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to
             taxanes and drugs chemically related to trametinib, or excipients or to dimethyl
             sulfoxide (DMSO)

          -  Current use of a prohibited medication. The following medications or non-drug
             therapies are prohibited:

               -  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, 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],
                  gingko biloba, dehydroepiandrosterone [DHEA], yohimbe, saw palmetto, or ginseng)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-Free Survival (PFS)
Time Frame:6 months
Safety Issue:
Description:PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first

Details

Phase:N/A
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Trametinib
  • Paclitaxel
  • 15-055

Last Updated

March 21, 2017