Cabozantinib-S-Malate in Treating Patients With Refractory Thyroid Cancer

Completed · Phase 2

Conditions studied: Poorly Differentiated Thyroid Gland Carcinoma, Recurrent Thyroid Gland Carcinoma, Stage I Thyroid Gland Follicular Carcinoma, Stage I Thyroid Gland Papillary Carcinoma, Stage II Thyroid Gland Follicular Carcinoma, Stage II Thyroid Gland Papillary Carcinoma, Stage III Thyroid Gland Follicular Carcinoma, Stage III Thyroid Gland Papillary Carcinoma, Stage IVA Thyroid Gland Follicular Carcinoma, Stage IVA Thyroid Gland Papillary Carcinoma, Stage IVB Thyroid Gland Follicular Carcinoma, Stage IVB Thyroid Gland Papillary Carcinoma, Stage IVC Thyroid Gland Follicular Carcinoma, Stage IVC Thyroid Gland Papillary Carcinoma, Tall Cell Variant Thyroid Gland Papillary Carcinoma, Thyroid Gland Oncocytic Follicular Carcinoma

In brief

This phase II trial studies how well cabozantinib-s-malate works in treating patients with thyroid cancer that does not respond to treatment. Cabozantinib-s-malate may stop the growth of thyroid cancer by blocking some of the enzymes needed for cell growth. Cabozantinib-s-malate may also stop the growth of thyroid cancer by blocking blood flow to the tumor.

Key facts

Study ID

NCT01811212

Run by

National Cancer Institute (NCI)

People needed

25

Starts

2013-05-08

Expected to finish

2017-10-09

Last updated by the study team

2018-04-03

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients must have histologically or cytologically confirmed papillary thyroid cancer, follicular thyroid cancer or hurthle cell thyroid cancer (cancer, follicular variant of papillary thyroid cancers or any of the above mixed histology will be allowed; these patients will be enrolled on Arm A of the trial); patients with the following aggressive histologies will be enrolled on Arm B of the trial; tall cell, insular or poorly differentiated thyroid cancer
• 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 >= 2.0 cm with conventional techniques or as >= 1.0 cm (or >= 1.5 cm in short axis for lymph node) with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
• Patients must have radioactive iodine (RAI)-refractory/resistant disease as defined by one or more of the following criteria:
• One or more measurable lesions that do not demonstrate RAI uptake
• One or more measurable lesions progressive by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 within 12 months of prior RAI therapy
• One or more measurable lesion present after cumulative RAI dose of >= 600 mCi
• Patients must have "progressed on" up to 2 lines of prior vascular endothelial growth factor receptor (VEGFR)-targeted therapy (including but not limited to sorafenib, sunitinib, vandetanib, pazopanib, or lenvatinib) as defined by progressive disease per RECIST while receiving VEGFR-targeted therapy; Note: patients who progressed on kinase inhibitor that target VEGFR and MET will not be eligible
• Prior external beam radiation, systemic cytotoxic chemotherapy or BRAF- or non-VEGFR-targeted therapies will be allowed, provided that >= 4 weeks has elapsed since receiving prior treatment and they have recovered to =< grade 1 treatment-related toxicities
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Absolute neutrophil count >= 1,500/mcL
• Platelet count >= 100,000/mcL
• Hemoglobin >= 9 g/dL
• Thyroid stimulating hormone (TSH) < lower limit of normal (LLN) (patients not able to tolerate TSH suppression can be granted an exception)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) (patients [Pts] with Gilbert's syndrome are excluded from this requirement)
• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3.0 x institutional upper limit of normal
• Creatinine =< 1.5 x ULN
• Serum albumin >= 2.8 g/dL
• Lipase < 2.0 x ULN and no radiologic or clinical evidence of pancreatitis
• Urine protein/creatinine ratio (UPCR) =< 1
• Serum phosphorus, calcium, magnesium and potassium >= LLN
• Prothrombin time (PT) < 1.3 x ULN
• International normalized ratio (INR) < 1.3 x ULN
• Partial thromboplastin time (PTT) test < 1.3 x ULN
• Women of childbearing potential must have a negative pregnancy test at screening; women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal; postmenopause is defined as amenorrhea >= 12 consecutive months; Note: women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, ovarian suppression or any other reversible reason
• Women of child-bearing potential and men must agree to use adequate contraception; women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation; 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; 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 cabozantinib administration; sexually active subjects (men and women) must agree to use medically accepted barrier methods of contraception (e.g., male or female condom) during the course of the study and for 4 months after the last dose of study drug(s), even if oral contraceptives are also used; all subjects of reproductive potential must agree to use both a barrier method and a second method of birth control during the course of the study and for 4 months after the last dose of study drug(s)

You may not qualify if…

• Prior treatment with cabozantinib or any tyrosine kinase inhibitor that targets MET or monoclonal antibody (mAb) targeting MET (such as onartuzumab [MetMAb])
• The subject has received radionuclide treatment =< 6 weeks of the first dose of study treatment
• The subject has received any other type of investigational agent =< 28 days before the first dose of study treatment
• The subject has not recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) =< grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant adverse events (AEs)
• The subject has active brain metastases or epidural disease; subjects with brain metastases previously treated with whole brain radiation or radiosurgery or subjects with epidural disease previously treated with radiation or surgery who are asymptomatic and do not require steroid treatment for at least 2 weeks before starting study treatment are eligible; baseline brain imaging with contrast-enhanced CT or MRI scans for subjects with known brain metastases is required to confirm eligibility; eligible patients with brain metastases can be taking anti-convulsant medications but only non-enzyme inducing anti-epileptic agents (NEIAED) will be allowed
• The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or factor xabans (Xa) inhibitors, or antiplatelet agents (e.g., clopidogrel); low dose aspirin (=< 81 mg/day), low-dose warfarin (=< 1 mg/day), and prophylactic low molecular weight heparin (LMWH) are permitted
• The subject requires chronic concomitant treatment of strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and St. John's Wort) or strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, voriconazole, and posaconazole); Note: because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated lists; 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
• The subject has experienced any of the following:
• Clinically-significant gastrointestinal bleeding =< 6 months before the first dose of study treatment
• Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood =< 3 months before the first dose of study treatment
• Any other signs indicative of pulmonary hemorrhage =< 3 months before the first dose of study treatment
• The subject has radiographic evidence of cavitating pulmonary lesion(s)
• The subject has tumor that is invading or encasing any major blood vessels
• The subject has evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor =< 28 days before the first dose of cabozantinib
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders including:
• Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening
• Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mmHg systolic, or > 90 mmHg diastolic despite optimal antihypertensive treatment =< 7 days of the first dose of study treatment
• Any history of congenital long QT syndrome
• Any of the following =< 6 months before the first dose of study treatment:
• Unstable angina pectoris
• Clinically-significant cardiac arrhythmias
• Stroke (including transient ischemic attack [TIA], or other ischemic event)
• Myocardial infarction
• Thromboembolic event requiring therapeutic anticoagulation (Note: subjects with a venous filter [e.g. vena cava filter] are not eligible for this study)

Where it is running

• MedStar Georgetown University Hospital — Washington D.C., District of Columbia, United States
• Mayo Clinic in Florida — Jacksonville, Florida, United States
• University of Chicago Comprehensive Cancer Center — Chicago, Illinois, United States
• Massachusetts General Hospital Cancer Center — Boston, Massachusetts, United States
• Mayo Clinic — Rochester, Minnesota, United States
• Ohio State University Comprehensive Cancer Center — Columbus, Ohio, United States
• M D Anderson Cancer Center — Houston, Texas, United States

Full record on ClinicalTrials.gov

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