Zanzalintinib in Unresectable and Progressive MPGGs

Starting soon · Phase 2

Conditions studied: Pheochromocytoma, Paraganglioma

In brief

This study is to examine the effects of oral daily zanzalintinib in participants with unresectable, progressive metastatic pheochromocytoma or paraganglioma.

Key facts

Study ID

NCT07714551

Run by

Dana-Farber Cancer Institute

People needed

14

Starts

2027-01-09

Expected to finish

2032-01-01

Last updated by the study team

2026-07-20

Who can join

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

You may qualify if…

• 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:
• Male: CrCl (mL/min) = (140 - age) × wt (kg) / (serum creatinine × 72) Female: Multiply above result by 0.85
• 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).

You may not qualify if…

• 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
• ·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 > 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.
• ·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 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

Where it is running

• Brigham and Women's Hospital (BWH) — Boston, Massachusetts, United States
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States

Full record on ClinicalTrials.gov

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