Cabozantinib S-malate in Treating Patients With Metastatic Pheochromocytomas or Paragangliomas That Cannot Be Removed by Surgery

NCT02302833 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2014-0081NCI-2014-02607
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot phase II trial studies how well cabozantinib s-malate works in treating patients with pheochromocytomas or paragangliomas that have spread from the primary site to other places in the body and cannot be removed by surgery. Cabozantinib s-malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking the growth of new blood vessels necessary for tumor growth.

Conditions

Locally Advanced Paraganglioma; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Paraganglioma; Regional Adrenal Gland Pheochromocytoma; Unresectable Adrenal Gland Pheochromocytoma; Unresectable Paraganglioma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  6 months

Study Arms (1)

Treatment (cabozantinib s-malate)

EXPERIMENTAL

Patients receive cabozantinib s-malate PO QD on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

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

Interventions

Cabozantinib S-malate DRUG

Given PO

Also known as: BMS-907351, Cabometyx, Cometriq, XL-184, XL184

Treatment (cabozantinib s-malate)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (cabozantinib s-malate)

Questionnaire Administration OTHER

Ancillary 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:

• Histological confirmation of pheochromocytoma (PH)/paraganglioma (PG)
• Locally advanced or metastatic disease not amenable to surgery
• Patients enrolled in the main branch should have measurable disease; patients with a predominance of bone disease who have small, non-measurable or small measurable lesions other than bone, may be included per the principal investigator's discretion, in the exploratory branch of the study for patients with bone metastases only
• Progressive disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as determined by the investigator within the 12 months preceding study enrollment
• Assessment of all known disease sites, e.g., by CT scan, MRI, bone scan as appropriate, and/or FDG-PET scan within 28 days before the first dose of cabozantinib
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Life expectancy of at least 3 months
• Absolute neutrophil count (ANC) \>= 1500/mm\^3 without colony stimulating factor support (within 4 days prior to the first dose of cabozantinib)
• Platelets \>= 100,000/mm\^3 (within 4 days prior to the first dose of cabozantinib)
• Hemoglobin \>= 9 g/dL (within 4 days prior to the first dose of cabozantinib)
• Bilirubin =\< 1.5 x the upper limit of normal (ULN) (for subjects with known Gilbert's disease, bilirubin =\< 3.0 mg/dL) (within 4 days prior to the first dose of cabozantinib)
• Serum albumin \>= 2.8 g/dl (within 4 days prior to the first dose of cabozantinib)
• Serum creatinine =\< 1.5 x ULN or creatinine clearance (CrCl) \>= 50 mL/min (for creatinine clearance estimation, the Cockcroft and Gault equation should be used) (within 4 days prior to the first dose of cabozantinib)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3.0 x ULN (within 4 days prior to the first dose of cabozantinib)
• Lipase \< 2.0 x ULN and no radiologic or clinical evidence of pancreatitis (within 4 days prior to the first dose of cabozantinib)

You may not qualify if:

• Received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) within 3 weeks, or nitrosoureas/mitomycin C within 6 weeks before the first dose of study treatment
• Prior treatment with cabozantinib
• Radiation therapy for bone metastasis within 2 weeks, or any other external radiation therapy within 4 weeks before the first dose of study treatment; subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible
• Received radionuclide treatment (i.e. iodine \[I\]-131 meta-iodo-benzyl guanidine) within 6 months of the first dose of study treatment
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 14 days before the first dose of study treatment
• Receipt of any other type of investigational agent within 28 days before the first dose of study treatment
• The subject has not recovered to baseline or CTCAE =\< grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant adverse events (AEs)
• Prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin time (PTT) test \>= 1.3 x the laboratory ULN within 7 days before the first dose of study treatment
• The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or Factor Xa inhibitors, or antiplatelet agents (eg, 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, rifapentine, phenobarbital, and St. John's wort)
• The subject has experienced any of the following: a. clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment, b. hemoptysis of \>= 0.5 teaspoon (2.5 ml) of red blood within 3 months before the first dose of study treatment, c. any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment
• Radiographic evidence of cavitating pulmonary lesion(s)
• Tumor invading or encasing any major blood vessels
• 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 within 28 days before the first dose of cabozantinib
• Uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions: a. cardiovascular disorders including: i. congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening, ii. concurrent uncontrolled hypertension defined as sustained blood pressure \> 150 mm Hg systolic, or \> 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment, iii. any history of congenital long QT syndrome, or iv. any of the following within 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, or thromboembolic event requiring therapeutic anticoagulation (note: subjects with a venous filter \[e.g. vena cava filter\] are not eligible for this study)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Jimenez C, Habra MA, Campbell MT, Tamsen G, Cruz-Goldberg D, Long J, Bassett R, Dantzer R, Balderrama-Brondani V, Varghese J, Lu Y. Cabozantinib in patients with unresectable and progressive metastatic phaeochromocytoma or paraganglioma (the Natalie Trial): a single-arm, phase 2 trial. Lancet Oncol. 2024 May;25(5):658-667. doi: 10.1016/S1470-2045(24)00133-5. Epub 2024 Apr 9.

  PMID: 38608693 DERIVED

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Pheochromocytoma; Paraganglioma

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Results Point of Contact

• Title: Dr. Camilo Jimenez
• Organization: The University of Texas MD Anderson Cancer Center

cjimenez@mdanderson.org

(713) 792-2841

Study Officials

• Camilo Jimenez

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: November 21, 2014
• First Posted: November 27, 2014
• Study Start: February 17, 2015
• Primary Completion: November 12, 2024
• Study Completion: November 12, 2024
• Last Updated: July 31, 2025
• Results First Posted: July 31, 2025

Record last verified: 2025-07

Locations

US (1)