Zanzalintinib for Unresectable Pheochromocytoma or Paraganglioma
This study is testing an oral medication called zanzalintinib for people with pheochromocytoma or paraganglioma (types of rare tumors) that cannot be removed by surgery and are getting worse. Zanzalintinib is taken once a day. The main goal is to see how many people respond to the treatment, which will be checked every 8 weeks for up to 16 months. About 14 adults aged 18 or older with a confirmed diagnosis of advanced pheochromocytoma or paraganglioma can join. Zanzalintinib is an investigational drug and is not yet approved by the FDA for any disease. The current status of the study is unclear.
- Study design
- This is a Phase II study where all 14 participants will receive zanzalintinib. It is a single-arm study, meaning there is no comparison group receiving a different treatment or placebo.
- What's involved
- You would have screening visits, physical exams, blood and urine tests, tumor imaging, and complete questionnaires. You would take zanzalintinib daily and have regular study visits for as long as the treatment is working and you don't have serious side effects.
- Compensation
- Not stated in the trial record.
- Follow-up
- After treatment ends, you will have a final visit within 30 days, followed by check-ups every 3 months for one year.
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NCT07714551
Zanzalintinib in Unresectable and Progressive MPGGs
Not Yet Recruiting
PHASE2Ages 18+InterventionalTreatmentDana-Farber Cancer InstituteInvestigator-initiated
~14 participants
Updated 2026-07-20 on ClinicalTrials.gov
What's tested:Zanzalintinib
At a glance
Recruiting sites
0 of 2 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Objective Response Rate (ORR)
Measured over Assessed every 8 weeks during treatment. The estimated treatment duration is up to 16 months.
Conditions
Where it's being run
2 sites across 1 statesMassachusetts2
Study leadership
- Kimbery Perez, MD · PRINCIPAL_INVESTIGATOR · Dana-Farber Cancer Institute
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Age ≥ 18 years. As no dosing or adverse event data are currently available in participants \< 18 years of age, children and adolescents are excluded from this study.
Documentation of Disease
Histologic Documentation: Histologically-proven advanced (metastatic or unresectable primary) pheochromocytoma or paraganglioma.
Stage: Advanced (metastatic or unresectable primary) disease
Tumor Site: Histologically-proven pheochromocytoma or paraganglioma
Radiographic Evaluation: Radiographic evidence of disease progression by RECIST v1.1 criteria in the 12 months prior to registration.
Measurable disease
Lesions must be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 1 cm with CT or MRI (or ≥ 1.5 cm for lymph nodes). Non-measurable disease includes disease smaller than these dimensions or lesions considered truly non-measurable including: leptomeningeal disease, ascites, pleural or pericardial effusion, lymphangitic involvement of skin or lung.
Prior Treatment
Prior treatment with other somatostatin analog, chemotherapy, radiotherapy (including peptide radionuclide receptor therapy \[PRRT\]), or surgery is permitted.
Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
Organ and marrow function and laboratory values as follows within 4 days prior to the first dose of zanzalintinib:
Absolute neutrophil count (ANC) ≥ 1500/mm3without colony stimulating factor support
Platelets ≥ 100,000/mm3
Hemoglobin ≥ 9 g/dL
Bilirubin ≤ 1.5 the upper limit of normal (ULN). For subjects with known Gilbert's disease, bilirubin ≤ 3.0 mg/dL
Serum albumin ≥ 2.8 g/dl
Serum creatinine ≤ 1.5 ULN or creatinine clearance (CrCl) ≥ 50 mL/min. For creatinine clearance estimation, the Cockcroft and Gault equation should be used:
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 ULN
Lipase \< 2.0 x the upper limit of normal and no radiologic or clinical evidence of pancreatitis
Urine protein/creatinine ratio (UPCR) ≤ 1
Serum phosphorus, calcium, potassium ≥ LLN and magnesium ≥ 1.2 mg/dL
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 (eg, 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. Post-menopause 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.
Exclusion
Received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (eg, cytokines or antibodies) within 3 weeks, or nitrosoureas/ mitomycin C within 6 weeks before the first dose of study treatment.
Prior treatment with zanzalintinib
Radiation therapy for bone metastasis within 2 weeks, 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. 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, fatigue, and other non-clinically significant AEs.
Prothrombin time (PT)/ International Normalized Ratio (INR) or partial thromboplastin time (PTT) test ≥ 1.3 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 antiplatelet agents (eg, clopidogrel). Low dose aspirin (≤ 81 mg/day), , prophylactic low molecular weight heparin (LMWH), and or specified direct Fxa inhibitors rivaroxaban, edoxaban, or apixabanare permitted in subjects without known brain metastases.
Subjects must have discontinued oral anticoagulants within 3 days or 5 half-lives prior to first dose of study treatment, whichever is longer.
The subject requires chronic concomitant treatment of strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and St. John's Wort).
Any complementary medications (eg, herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks before first dose of study treatment.
Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment. Note: Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of enrollment. Note: Base of skull lesions without definitive evidence of dural or brain parenchymal involvement are allowed.
The subject has experienced any of the following: clinically significant gastrointestinal bleeding within 6 months before the first dose of study treatment hemoptysis of ≥ 0.5 teaspoon (2.5ml) of red blood within 3 months before the first dose of study treatment
Radiographic evidence of cavitating pulmonary lesion(s)
Tumor invading or encasing \> 180 degrees any major blood vessels
Evidence of tumor invading the 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 zanzalintinib.
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 BP \> 150 mm Hg systolic, or \> 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment
Any history of congenital long QT syndrome
Any of the following within 6 months before the first dose of study treatment:
unstable angina pectoris
clinically-significant cardiac arrhythmias
stroke (including 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)
Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:
intra-abdominal tumor/metastases invading GI mucosa
known gastric or esophageal varices, ascites, pleural effusion, or pericardial fluid requiring drainage in last 4 weeks
active peptic ulcer disease; patients must be completely recovered
acute flare of inflammatory bowel disease (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis; patients must be completely recovered from these conditions
malabsorption syndrome
abdominal fistula
gastrointestinal perforation
bowel obstruction or gastric outlet obstruction
intra-abdominal abscess. Note: Complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with zanzalintinib even if the abscess occurred more than 6 months before the first dose of study treatment.
Other disorders associated with a high risk of fistula formation including PEG tube placement within 3 months before the first dose of study therapy
Other clinically significant disorders such as:
Active infection requiring systemic treatment within 28 days before the first dose of study treatment.
Known infection with acute or chronic hepatitis B or C, known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness except for subjects meeting all of the following criteria: (1) on stable anti-retroviral therapy; (2) CD4+ T cell count ≥ 200/µL; and (3) an undetectable viral load. Note: HIV testing will be performed at screening if and as required by local regulation. Note: To be eligible, participants taking CYP inhibitors (eg, zidovudine, ritonavir, cobicistat, didanosine) or CYP3 inducers (efavirenz) must change to a different regimen not including these drugs 7 days prior to initiation of study treatment. Anti-retroviral therapies (ART) must have been received for at least 4 weeks prior to the first dose. Note: CD4+ T cell counts, and viral load are monitored per standard of care by the local health care provider. Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment
History of organ transplant
Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment
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 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.
Moderate to severe hepatic impairment (Child-Pugh B or C).
Requirement for hemodialysis or peritoneal dialysis.
What this trial measures
- Objective Response Rate (ORR)Assessed every 8 weeks during treatment. The estimated treatment duration is up to 16 months.
ORR was defined as the percentage of participants achieving complete response (CR) or partial response (PR) on treatment based on RECIST 1.1 criteria. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.