Inolitazone Dihydrochloride and Paclitaxel in Treating Patients With Advanced Anaplastic Thyroid Cancer

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 2

Conditions: Recurrent Thyroid Cancer; Anaplastic Thyroid Cancer

Treatments: Drug: efatutazone; Drug: paclitaxel

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT02152137

NCI-2014-00686 (Registry Identifier)

U10CA031946 (U.S. NIH Grant/Contract)

A091305

U10CA180821 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

This phase II trial studies how well inolitazone dihydrochloride (efatutazone dihydrochloride) and paclitaxel work in treating patients with anaplastic thyroid cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced). Drugs used in chemotherapy, such as efatutazone dihydrochloride and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Full description

PRIMARY OBJECTIVES:

I. To determine if the combination of paclitaxel and efatutazone (efatutazone dihydrochloride) improves the confirmed response rate in patients with advanced anaplastic thyroid cancer.

SECONDARY OBJECTIVES:

I. To estimate the overall survival (OS), duration of response, progression-free survival (PFS), and adverse event rates for the combination of paclitaxel and efatutazone.

TERTIARY OBJECTIVES:

I. The association of biomarkers with clinical outcome data will be assessed in an exploratory translational analysis.

OUTLINE:

Patients receive paclitaxel intravenously (IV) over 3 hours on day 1 and efatutazone dihydrochloride orally (PO) twice daily (BID) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up within 28 days, every 8 weeks until disease progression, and then every 6 months for 5 years.

Enrollment: 19 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

• Patients must have histologically or cytologically diagnosed advanced anaplastic thyroid cancer (ATC)

• Patients must have measurable disease

• Patients must have either metastatic (stage IVC) or locally advanced unresectable disease (stage IVB)

• Patients should have resolution of any toxic effects of prior therapy (except alopecia) to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, grade 1

• There is no limit to the number of prior lines of treatment a patient has received

• No treatment with chemotherapy, radiation therapy, immunotherapy, biological therapy, hormonal therapy, or other thiazolidinediones (TZDs) =< 21 days before study registration

• No prior taxane therapy =< 6 months, except as a radiosensitizer

• No history of the following:

  • Class III or IV congestive heart failure (CHF)
  • Grade 3 or 4 thromboembolic event =< 6 months
  • Pericardial effusion =< 12 months (any grade)
  • Pericardial involvement with tumor
  • Grade 2 or higher pleural effusion =< 6 months

• No current symptomatic, untreated, or uncontrolled brain metastases present

• No major surgery =< 14 days prior to registration

• No grade 2 or higher neuropathy

• No known history of severe hypersensitivity reactions to any of the components of efatutazone or paclitaxel formulations

• Not pregnant and not nursing; women of childbearing potential only, a negative pregnancy test done =< 7 days prior to registration is required

• Patients with diabetes mellitus requiring concurrent treatment with insulin or thiazolidinedione (TZD) oral agents are not eligible

• Patients with known hypersensitivity to any TZD oral agents are not eligible

• Eastern Cooperative Oncology Group (ECOG) performance status =< 2

• Absolute neutrophil count (ANC) >= 1,500/mm^3

• Platelet count >= 100,000/mm^3

• Creatinine =< 1.5 x upper limit of normal (ULN) mg/dL OR calculated (calc.) creatinine clearance >= 60 mL/min

• Bilirubin =< 1.5 x ULN

• Aspartate aminotransferase (AST) =< 2.5 x ULN

• Although they will not be considered formal eligibility (exclusion) criteria, physicians should recognize that the following may seriously increase the risk to the patient entering this protocol:

  • Psychiatric illness which would prevent the patient from giving informed consent
  • Medical condition such as uncontrolled infection (including human immunodeficiency virus [HIV]), uncontrolled diabetes mellitus or cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
  • Patients with a "currently active" second malignancy other than non-melanoma skin cancers; patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for >= 3 years; there is an exception for patients with a history of well differentiated thyroid cancer that has progressed to anaplastic thyroid cancer
  • Patients who cannot swallow oral formulations of the agent(s)
  • Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study ; appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives or double barrier method (diaphragm plus condom)
  • Efatutazone is metabolized by cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5), and inhibits CYP2C8, 2C9, 2C19, and 3A4, and is a substrate of P-glycoprotein (PgP) and breast cancer resistance protein (BCRP)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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19 participants in 1 patient group

efatutazone dihydrochloride, paclitaxel

Experimental group

Description:

Patients receive paclitaxel IV over 3 hours on day 1 and efatutazone dihydrochloride PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Treatment:

Drug: paclitaxel

Drug: efatutazone