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

NCT01811212 | Completed Phase 2 Results DMC

• 11 other identifiers: NCI-2013-005542012C0101RU241210IOSU 121549312N01CM00039N01CM00070N01CM00071N01CM00099P30CA016058UM1CA186705
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate, Defined as the Proportion of Patients Who Have Had a PR or CR as Assessed by the RECIST Version (v)1.1

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

  Up to 6 months

Secondary Outcomes (9)

• Bone Turnover, as Measured by Serum and Urinary Markers of Bone Turnover

  Up to 2 months

• Duration of Objective Response as Assessed by the RECIST v1.1

  From date of documentation of response to the date of progression or death, assessed up to 1 year

• Expression Levels of Predictive Biomarkers of Response by Immunohistochemistry in Archived Tumor Tissue

  Baseline

• Genotype of Biomarkers Potentially Predictive of Response

  Baseline

• Incidence of Severe (Grade 3+) Adverse Events, Graded According to the National Cancer Institute CTCAE v4.0

  Up to 1 year

Study Arms (1)

Treatment (cabozantinib-s-malate)

EXPERIMENTAL

Patients receive cabozantinib-s-malate PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Cabozantinib S-malate; Other: Laboratory Biomarker Analysis

Interventions

Cabozantinib S-malate DRUG

Given PO

Treatment (cabozantinib-s-malate)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (cabozantinib-s-malate)

Eligibility Criteria

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

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

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:

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• Exelixis: collaborator

Study Sites (7)

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Cabanillas ME, de Souza JA, Geyer S, Wirth LJ, Menefee ME, Liu SV, Shah K, Wright J, Shah MH. Cabozantinib As Salvage Therapy for Patients With Tyrosine Kinase Inhibitor-Refractory Differentiated Thyroid Cancer: Results of a Multicenter Phase II International Thyroid Oncology Group Trial. J Clin Oncol. 2017 Oct 10;35(29):3315-3321. doi: 10.1200/JCO.2017.73.0226. Epub 2017 Aug 17.

  PMID: 28817373 RESULT

MeSH Terms

Conditions

Thyroid Neoplasms; Adenocarcinoma, Follicular; Thyroid Cancer, Papillary; Thyroid cancer, Hurthle cell

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Adenocarcinoma, Papillary

Results Point of Contact

• Title: Manisha Shah, MD
• Organization: The Ohio State University Compreshive Cancer Center

manisha.shah@osumc.edu

614-366-6994

Study Officials

• Manisha Shah

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2013
• First Posted: March 14, 2013
• Study Start: May 8, 2013
• Primary Completion: July 13, 2015
• Study Completion: October 9, 2017
• Last Updated: April 3, 2018
• Results First Posted: April 3, 2018

Record last verified: 2018-03

Locations

US (7)