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New treatment option for Bone Sarcomas
Official title A Phase 2 Trial of Zanzalintinib in Advanced/Metastatic Bone Sarcomas (ZAMBONE)
ClinicalTrials.gov ID: NCT07193550
What this study is testing
What is Zanzalintinib?
Zanzalintinib is an investigational medicine, given as an once-daily pill taken by mouth, being studied as a potential treatment for bone sarcomas.
Also referred to as XL092.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- To study the treatment efficacy of zanzalintinib monotherapy in patients with advanced and/or metastatic bone sarcomas.
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- Patients ≥ 18 years old with pathologically confirmed unresectable locally advanced or metastatic bone sarcoma in one of the following categories...
- Patients with conventional chondrosarcoma (Cohort C) must demonstrate evidence of disease progression by RECIST 1.1 within 12 weeks of trial...
- Patients must have relapsed or become refractory to conventional therapy, receiving at least 1 prior line of systemic therapy unless no standard of...
- Patients may have received no more than 2 prior lines of systemic therapy in the advanced/metastatic setting.
- Multi-agent and/or alternating neoadjuvant/adjuvant standard of care chemotherapy will be counted as 1 line of systemic therapy if given for...
You likely can't join if
- Prior treatment with zanzalintinib.
- Patients with primary soft tissue sarcoma with metastasis to bone. o Patients with histologically confirmed Ewing's sarcoma with either bone or soft...
- Patients with known sensitivity to the study agents and/or previously identified allergy or hypersensitivity to components of treatment
- Patients previously treated with other VEGF-targeted TKIs (including but not limited to cabozantinib, regorafenib, pazopanib, or similar).
- Receipt of any small molecule kinase inhibitor (including investigational within 2 weeks before first dose of study treatment.
- Untreated central nervous system metastatic disease, leptomeningeal disease, or cord compression.
See the full eligibility criteria
Who can join
- Patients ≥ 18 years old with pathologically confirmed unresectable locally advanced or metastatic bone sarcoma in one of the following categories: Cohort A - Osteosarcoma, Cohort B - Ewing sarcoma, Cohort C -...
- Patients with conventional chondrosarcoma (Cohort C) must demonstrate evidence of disease progression by RECIST 1.1 within 12 weeks of trial enrollment
- Patients must have relapsed or become refractory to conventional therapy, receiving at least 1 prior line of systemic therapy unless no standard of care exists.
- Patients may have received no more than 2 prior lines of systemic therapy in the advanced/metastatic setting.
- Multi-agent and/or alternating neoadjuvant/adjuvant standard of care chemotherapy will be counted as 1 line of systemic therapy if given for metastatic disease. Otherwise, neoadjuvant/adjuvant chemotherapy for localized...
- Patients must have a performance status corresponding to ECOG scores of 0, 1 or 2 (Karnofsky ≥60%).
- Weight \>/= 40 kg.
- Patients must have measurable disease per RECIST v1.1
- Prior radiation will be allowed assuming there is measurable disease based upon RECIST 1.1 and at least 21 days from the completion of all radiation prior to initiation of study treatment. (Note: Previously irradiated...
- Hematological function, as follows:
- Absolute neutrophil count (ANC) ≥ 1500/mm3 (growth factor/G-CSF permitted)
- Platelet count ≥ 100,000/mm3
- Hemoglobin \> 9 g/dL.
- INR ≤ 1.5 and activated partial thromboplastin time (aPTT) \< 1.2 x upper limit of normal (ULN), except people on anticoagulation.
- Renal function as follows: calculated creatinine clearance ≥ 40 mL/min (≥ 0.67 mL/sec) using the Cockcroft Gault equation.
- Hepatic function as follows: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 x ULN and total bilirubin ≤ 1.5 x ULN (for people with Gilberts's disease ≤ 3 x ULN), serum albumin ≥ 2.
- All patients must agree to consent and co-enroll on MD Anderson MOSAIC protocol to allow for sample collection and correlative studies
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral...
- Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.
- Patients with a prior malignancy whose natural history or treatment does not have the potential to interfere with the safety or how well it works assessment of the investigational regimen are eligible for this trial.
- Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association...
- Female people of childbearing potential must not be pregnant at screening. Female people are considered to be of childbearing potential unless one of the following criteria is met: permanent sterilization (hysterectomy...
- Sexually active fertile people and their partners must agree to use highly effective method of contraception (hormonal or barrier method of birth control, intrauterine device, tubal ligation or hysterectomy...
- Postmenopausal (no menses in greater than or equal to 12 consecutive months).
- History of hysterectomy or bilateral salpingo-oophorectomy.
- Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
- History of bilateral tubal ligation or another surgical sterilization procedure. In addition, men must agree not to donate sperm through 96 days after the last dose of zanzalintinib and women (WOCBP) must agree not to...
- Ability to understand and the willingness to sign a written informed consent document.
What rules you out
- Prior treatment with zanzalintinib.
- Patients with primary soft tissue sarcoma with metastasis to bone. o Patients with histologically confirmed Ewing's sarcoma with either bone or soft tissue primary site are eligible for enrollment in Cohort B
- Patients with known sensitivity to the study agents and/or previously identified allergy or hypersensitivity to components of treatment
- Patients previously treated with other VEGF-targeted TKIs (including but not limited to cabozantinib, regorafenib, pazopanib, or similar).
- Receipt of any small molecule kinase inhibitor (including investigational within 2 weeks before first dose of study treatment.
- Untreated central nervous system metastatic disease, leptomeningeal disease, or cord compression.
- Active infection requiring intravenous (IV) antibiotics within 2 weeks of study enrollment.
- Prior receipt of an investigational study drug and/or procedure within 21 days of study day 1.
- Anti-tumor therapy within 21 days of study day 1 including chemotherapy, antibody therapy, or other investigational agent.
- Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks, or systemic treatment with radionuclides within 6 weeks before first dose of study treatment; ongoing clinically relevant...
- Any complementary medicine such as herbal supplements, Chinese medicines, or other non-prescription medications being used for the treatment of bone sarcoma within 2 weeks prior to first dose of treatment as detailed in...
- History of cardiac disease: congestive heart failure New York Heart Association (NYHA) class \> II, unstable angina (angina symptoms at rest), new-onset angina (within the past 6 months before study entry), myocardial...
- Uncontrolled hypertension defined as sustained blood pressure (BP) \> 140 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment
- Moderate or severe hepatic impairment, i.e. Child-Pugh class B or C.
- Patients with known human immunodeficiency virus (HIV) infection with detectable viral load. HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this...
- Known infection with acute or chronic hepatitis B or C.
- History of solid organ or allogeneic stem cell transplant
- Any other known concurrent or prior malignancy at time of or within 2 years of first does of study treatment. Prior malignancy that is in remission or otherwsie has not required treatment in \> 2 years will be permitted.
- Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before first dose of...
- Pulmonary embolism (PE) or deep vein thrombosis (DVT) or prior clinically significant venous events within 3 months before first dose of study treatment. Note, patients with a diagnosis of incidental, subsegmental PE or...
- Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
- Tumors invading the GI-tract from external viscera
- Active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or acute pancreatitis
- Acute obstruction of the bowel, gastric outlet, or pancreatic or biliary duct within 6 months before first dose unless cause of obstruction is definitively managed and asymptomatic
- Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months of the first dose. Note, complete healing of an intra-abdomninal abscess must be confirmed before first dose of study...
- Known gastric or esophageal varices
- Ascites, pleural effusion, or pericardial effusion requiring drainage in last 4 weeks
- Clinically significant hematuria, hematemesis, or hemoptysis of \> 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 12 weeks before first dose of study...
- Symptomatic cavitating pulmonary lesion(s) or endobronchial disease. Note, asymptomatic or radiated lesions allowed
- Lesions invading major blood vessel including but not limited to inferior vena cava, pulmonary artery, or aorta. Note, patients with intravascular tumor extension (i.e. tumor thrombus in renal vein or inferior vena...
- Other clinically significant disorders that would preclude safe study participation:
- Serious non-healing wound, ulcer, or bone fracture. Note, non-healing wounds or ulcers may be permitted if due to tumor associated skin lesions
- Malabsoprtion syndromes
- Pharmacologically uncompensated, symptomatic hypothyroidism
- Requirement for hemodialysis or peritoneal dialysis
- History of solid organ or allogeneic stem cell transplant
- Major surgery (i.e. GI surgery, removal or biopsy of brain metastasis) within 8 weeks prior to first dose of study treatment. Prior laproscopic surgeries withint 4 weeks prior to first dose of study treatment. Minor...
- Corrected QT interval calculated by the Fridericia formula (QTcF) \> 470 ms within 14 days per electrocardiogram (ECG) before first dose of study treatment. Note: Triplicate ECG evaluations will be performed and the...
- Patients with psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant or lactating women are excluded from this study because zanzalintinib is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events...
- Inability to swallow tablets or ingest a suspension either orally or by nasogastric (NG) or gastronomy (PEG) tube.
- Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin inhibitors ) and platelet inhibitors (eg, clopidogrel). Allowed anticoagulants are the following:
- Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
- Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in people without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week...
- Note, people must have discontinued prohibited oral anticoagulants at least 3 days or 5 half-lives prior to the first dose of study treatment, whichever is longer
- Proteinuria \> 1g/day.
- Other conditions, which in the opinion of the investigator, would compromise the safety of the patient's ability to complete the study
The study team makes the final eligibility decision.
Where it's taking place
- Houston, Texas, United States
Compensation & support
A stipend or compensation may be offered.
Compensation mentioned.
ClinicalTrials.gov doesn't provide a reliable structured field for payment or travel support - confirm details with the study team.
Questions & answers
Do participants get paid in this trial?
This study's listing includes signals that participants may be compensated or receive a stipend. Amounts vary and are set by the study team - confirm the details with them.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Houston, Texas, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.