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Locally Advanced ParagangliomaPhase 2NCT02302833

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

A Phase 2 study testing Cabozantinib S-malate, Laboratory Biomarker Analysis and Questionnaire Administration in people with Locally Advanced Paraganglioma and Metastatic Adrenal Gland Pheochromocytoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cabozantinib S-malate, Laboratory Biomarker Analysis and Questionnaire Administration
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
1 siteUnited States
Study dates
17 Feb 2015to 12 Nov 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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)
  • Urine protein/creatinine ratio (UPCR) =< 1 (within 4 days prior to the first dose of cabozantinib)
  • Serum phosphorus, calcium, potassium >= lower limit of normal (LLN) (within 4 days prior to the first dose of cabozantinib)
  • Serum magnesium >= 1.2 mg/dL (within 4 days prior to the first dose of cabozantinib)
  • Capable of understanding and complying with the protocol requirements and has signed the informed consent document
  • Sexually active patients (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)
  • 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

Who cannot join

  • 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
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  • 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)
  • Gastrointestinal disorders, particularly those associated with a high risk of perforation or fistula formation, including: i. any of the following within 28 days before the first dose of study treatment: intra-abdominal tumor/metastases invading GI mucosa, active peptic ulcer disease (patients must be completely recovered), inflammatory bowel disease (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis (patient must be completely recovered from these conditions), malabsorption syndrome; ii. any of the following within 6 months before the first dose of study treatment: abdominal fistula, gastrointestinal perforation, bowel obstruction or gastric outlet obstruction, or intra-abdominal abscess (complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more than 6 months before the first dose of study treatment); c. other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months before the first dose of study therapy, d. other clinically significant disorders such as: i. active infection requiring systemic treatment within 28 days before the first dose of study treatment, ii. serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment, iii. history of organ transplant, iv. concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment, or v. major surgery within 12 weeks before the first dose of study treatment; complete wound healing from major surgery must have occurred 1 month before the first dose of study treatment; minor surgery within 28 days before the first dose of study treatment with complete wound healing at least 10 days before the first dose of study treatment; subjects with clinically relevant ongoing complications from prior surgery are not eligible
  • Unable to swallow tablets
  • A corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before first dose of study treatment; three electrocardiograms (ECGs) must be performed; if the average of these three consecutive results for QTcF is =< 500 msec, the subject meets eligibility in this regard
  • Pregnant or breastfeeding
  • A previously identified allergy or hypersensitivity to components of the study treatment formulation
  • Unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee
  • Evidence within 2 years of the start of study treatment of another malignancy which required systemic treatment except for cured nonmelanoma skin cancer or cured in situ cervical carcinoma
  • Any other severe acute or chronic medical or psychiatric condition or laboratory abnormality which, in the judgment of the investigator, would have made the patient inappropriate for entry into this study

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase II Study to Evaluate the Effects of Cabozantinib in Patients With Unresectable Metastatic Pheochromocytomas and Paragangliomas

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To estimate best overall response rate in patients with measurable disease determined by computed tomography (CT) or magnetic resonance imaging (MRI).

SECONDARY OBJECTIVES:

  1. To estimate progression-free survival at 1-year. II. To correlate blood pressure control and change/discontinuation of antihypertensive medications with tumor responses.

III. To correlate symptomatology evaluation by the MD Anderson Symptom Inventory (MDASI) with tumor responses.

IV. To correlate plasma metanephrines and chromogranin A with tumor responses. V. To correlate plasma C-reactive protein and interleukin-6 with symptoms and tumor responses.

VI. Toxicity assessment by the Common Terminology Criteria for Adverse Events (CTCAE).

VII. To correlate both c-MET expression by immunohistochemistry (IHC) as well as MET amplification by fluorescence in situ hybridization (FISH) in archived samples and correlate these biomarkers with overall prognosis and responsiveness to cabozantinib (cabozantinib s-malate).

EXPLORATORY OBJECTIVES:

  1. Best overall response rate in patients with bone metastases only (8 patients) as determined by fludeoxyglucose F 18 positron emission tomography/computed tomography (FDG-PET/CT).

II. FDG-PET/CT maximum standard uptake value (SUVmax), advanced volumetric measures including peak standard uptake value (SUVpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG).

III. Time to skeletal related events. IV. Incidence of skeletal related events at 4 months and one year. V. Markers of bone turnover (bone specific alkaline phosphatase and C-terminal telopeptide [CTx]).

OUTLINE:

Patients receive cabozantinib s-malate orally (PO) once daily (QD) on days 1-28. Courses repeat every 4 weeks through week 24 and then every 8 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30-37 days.

Being tested
Cabozantinib S-malate, Laboratory Biomarker Analysis, Questionnaire Administration
Medical subject headings
Pheochromocytoma, Paraganglioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cabozantinib S-malateDrug

    Also called BMS-907351, Cabometyx, Cometriq, XL-184

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Questionnaire AdministrationOther

    Ancillary studies

Study groups in NCT02302833
Study groupRoleWhat they receive
Treatment (cabozantinib s-malate)ExperimentalPatients receive cabozantinib s-malate PO QD on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Cabozantinib S-malate; Other: Laboratory Biomarker Analysis; Other: Questionnaire Administration

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Nov 2014 (estimated)
  2. Study start17 Feb 2015
  3. Primary completion12 Nov 2024
  4. Study completion12 Nov 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02302833
Sponsor's protocol ID
2014-0081
Other IDs
NCI-2014-02607, 2014-0081
Status last verified
Jul 2025
First submitted
21 Nov 2014
Last updated
31 Jul 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 38608693

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cabozantinib S-malate, Laboratory Biomarker Analysis and Questionnaire Administration in people with Locally Advanced Paraganglioma and Metastatic Adrenal Gland Pheochromocytoma, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02302833, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2025.

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