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

NCT03085056 | Active Not Recruiting Early Phase 1 FDA Drug

• 1 other identifier: 15-055
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Anaplastic Thyroid Cancer

Keywords

Trametinib; Paclitaxel; 15-055

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first

  6 months

Study Arms (1)

Trametinib in Combination With Paclitaxel

EXPERIMENTAL

Patients 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.

Drug: Trametinib; Drug: Paclitaxel

Interventions

Trametinib DRUG

trametinib orally 2mg daily during each 4 week cycle

Trametinib in Combination With Paclitaxel

Paclitaxel DRUG

paclitaxel 80mg/m\^2 weekly for 3 out of 4 weeks

Trametinib in Combination With Paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 (or 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

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 7 days of starting treatment.
• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Novartis: collaborator

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Cancer Center @ Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Thyroid Carcinoma, Anaplastic

Interventions

trametinib; Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Eric Sherman, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a 12 patient pilot study that will evaluate the combination of the MEK inhibitor trametinib with paclitaxel in anaplastic thyroid cancer.

Study Record Dates

• First Submitted: March 15, 2017
• First Posted: March 21, 2017
• Study Start: March 15, 2017
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: July 3, 2025

Record last verified: 2025-07

Locations

US (7)