Cabozantinib Maintenance Therapy vs Best Supportive Care in Osteosarcoma Patients in Complete Remission or with Residual Disease after First‑Line Chemotherapy
The study focuses on Osteosarcoma, a type of bone cancer that often affects children and young adults. After standard chemotherapy, participants may receive the oral drug cabozantinib or receive best supportive care as a maintenance option. The purpose of the study is to determine whether adding the drug improves event-free survival, meaning the length of time a person lives without the cancer returning or without dying.
Participants who have finished first‑line chemotherapy and are either in complete remission (no detectable cancer) or have stable disease are randomly assigned to one of the two groups. They take the study medication daily for a defined period while regular check‑ups, scans, and questionnaires about quality of life are performed. The study follows each participant for several years to record any return of cancer, new health problems, or death, and the information is used to compare the two treatment approaches.
1enrollment and consent
after joining the study, you sign a consent form that explains the purpose of the research and your responsibilities.
the study team records your basic information and confirms that you meet the eligibility criteria for osteosarcoma.
2baseline assessments
you undergo clinical examinations, imaging tests, and blood sampling to document the status of your disease before any study treatment.
questionnaires about quality of life and functional outcome are completed to provide reference data for later comparison.
3randomization to treatment arm
based on the study design, you are assigned either to the cabozantinib arm or to the best supportive care arm.
the assignment is made by a computer system and is not influenced by the study staff.
4maintenance therapy with cabozantinib (if assigned)
if you are assigned to the cabozantinib arm, you receive cabometyx 60 mg film‑coated tablets for oral use.
the tablet is taken once daily, swallowed with water, and you continue this medication until disease progression, unacceptable side effects, or the end of the study period as determined by the investigators.
if you are assigned to the best supportive care arm, you do not receive cabozantinib but receive standard supportive measures to manage symptoms.
5regular follow‑up and monitoring
you attend scheduled follow‑up visits where clinical examinations, imaging, and laboratory tests are repeated to monitor disease status and safety.
during each visit you complete quality‑of‑life questionnaires and report any side effects or new symptoms.
the study team records any adverse events, and serious events are reported promptly according to the study protocol.
6study completion
the trial continues for up to three years after enrollment, or until disease progression, death, or withdrawal from the study.
at the end of the study period, final assessments are performed and the collected data are analyzed to evaluate event‑free survival and other outcomes.
Who Can Join the Study?
You have a new diagnosis of osteosarcoma that has been confirmed by a biopsy and is classified as high‑grade (aggressive) tumor.
You are at least 4 years old and able to swallow tablets; there is no upper age limit.
You are medically fit to receive systemic (whole‑body) cancer treatment according to national guidelines.
You have finished the first‑line chemotherapy and any surgery, radiation, or thermoablation for the primary tumor (and any metastases) as recommended by your doctors.
You have recovered from any side effects of the previous treatment to at most mild (grade 0‑1) level, except hair loss, mild anemia, or low thyroid hormone, which are allowed to remain.
Your performance status is better than 2 for adults, or you have a Karnofsky/Lansky score above 70, meaning you can carry out most daily activities.
The time since your last cancer treatment (chemotherapy, surgery, radiation, or thermoablation) is at least 4 weeks but not more than 2 months before randomisation.
Your disease is either in complete remission (no detectable cancer) or has stable disease that is not getting worse, as measured by RECIST criteria (a standard way doctors measure tumor size).
You are fit to undergo the study treatment and attend follow‑up visits.
Your heart function is adequate: left ventricular ejection fraction (LVEF) ≥ 50% or fractional shortening (FS) > 28%, measured by an echocardiogram or a MUGA scan if echo is not possible.
Your blood pressure is well controlled – for children, below the 95th percentile for age, sex, and height; for adults, ≤ 150/90 mmHg – and you have not changed blood‑pressure medicines within one week before starting the study.
Laboratory tests taken within 7 days before randomisation meet these limits:
White blood cells (neutrophils) ≥ 1 × 10⁹/L.
Platelets ≥ 100 × 10⁹/L.
Hemoglobin ≥ 8.0 g/dL (or can be raised with growth factor or transfusion before start).
Kidney function: serum creatinine ≤ 1.5 × upper normal limit, or if higher, calculated creatinine clearance or glomerular filtration rate (GFR) > 60 mL/min/1.73 m².
Urine protein less than 2+ on dipstick; if 2+ or more, a spot protein/creatinine ratio must be grade 2 or lower.
No clinical evidence of nephrotic syndrome (a kidney disorder causing large protein loss).
Liver enzymes (ALT/AST) ≤ 2.5 × upper normal limit (or ≤ 5 × if liver metastases are present).
Total bilirubin ≤ 1.5 × upper normal limit (or ≤ 5 × if liver metastases are present; higher allowed in Gilbert syndrome).
Alkaline phosphatase ≤ 2.5 × upper normal limit (or ≤ 5 × if liver involvement); if higher, GGT must be < 1.5 × upper limit.
Lipase ≤ 1.5 × upper normal limit.
Blood clotting tests (INR/PTT) ≤ 1.5 × upper normal limit.
If you are taking blood‑thinning medicines such as warfarin, heparin, or low‑molecular‑weight heparin (LMWH), you may still join as long as you have no abnormal clotting test results before the study.
Women who could become pregnant (or have started menstruation) must have a negative pregnancy test (blood or urine) done within 7 days before randomisation; the test detects human chorionic gonadotropin (HCG).
Effective contraception must be used by both men and women (and their partners) during treatment and for at least 4 months after the study ends. Oral contraceptives should be combined with another method such as condoms, as advised by a doctor.
You must provide a dated and signed informed consent form before any study procedures are performed.
You must be enrolled in a social insurance or equivalent health‑coverage plan if required in your country.
Who Cannot Join the Study?
Low‑grade osteosarcoma, parosteal or periosteal osteosarcoma, or small cell osteosarcoma – these less aggressive types of bone cancer are not allowed in the study.
Serious unrelated illness such as a severe infection, major heart, lung, liver, or other organ problems that would make it hard to take the study medicine or follow the study procedures.
Use of prohibited medicines that are not allowed while participating in the trial.
Progressive disease that gets worse at any site during initial chemotherapy, unless the tumor is only growing before surgery and can be completely removed.
Being pregnant, breastfeeding, or planning to become pregnant during the study.
Any psychological, family, social, or travel issues that could prevent you from following the study schedule.
History of not following medical instructions or being unwilling or unable to follow the study plan.
Being under legal guardianship, court‑ordered confinement, or unable to give consent on your own.
Previous treatment with any VEGF (vascular endothelial growth factor) inhibitor such as sunitinib, sorafenib, pazopanib, regorafenib, bevacizumab, or similar drugs.
Heart or blood‑vessel problems (cardiovascular dysfunction).
Uncontrolled high blood pressure that remains above the 95th percentile despite medication (for adults, systolic >150 mm Hg or diastolic >90 mm Hg).
Active or chronic hepatitis B or C that requires antiviral treatment.
Recent serious blood‑clot events (arterial or venous) such as stroke, transient ischemic attack, deep‑vein thrombosis, or pulmonary embolism within the past 6 months.
Major surgery or a serious injury within the last 3 weeks, or a wound that has not yet healed.
Ongoing infection that is more than moderate severity (greater than Grade 2) unless fully recovered before starting the study drug.
Known infection with HIV (human immunodeficiency virus).
Allergy (hypersensitivity) to the study drug or any of its inactive ingredients.
Significant dehydration (more than mild, Grade >1).
Difficulty swallowing pills, any condition that prevents proper absorption of medicine, or serious gastrointestinal problems such as ulcers, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or removal of part of the small intestine.
Having a seizure disorder that requires medication.
Current signs or symptoms of interstitial lung disease (a group of lung disorders that cause scarring and breathing problems).
Any non‑healing wound, ulcer, or bone fracture.
Any history of a bleeding tendency (bleeding diathesis) regardless of how severe.
Any bleeding event that was Grade 3 or higher (moderate to severe) within the 4 weeks before the first dose of the study drug.
CABOMETYX is an oral medicine that contains the active ingredient cabozantinib. In this study it is given after the initial chemotherapy to help keep the cancer from coming back. The drug works by blocking certain signals that cancer cells need to grow and spread, so it may help patients stay disease‑free for a longer time.
Best Supportive Care (BSC) is not a specific drug but a collection of treatments and services that aim to keep patients comfortable and manage any symptoms or side effects they may have. In the trial, BSC is used as the comparison treatment to see whether adding CABOMETYX provides extra benefit in preventing cancer recurrence.
Osteosarcoma – Osteosarcoma is a cancer that starts in the cells that form bone. It most often appears in the long bones near the knee or shoulder. The tumor grows by producing abnormal bone tissue that can become hard and painful. As it enlarges, it can break through the bone surface and spread to nearby tissues. In some cases it can travel through the bloodstream to other parts of the body, such as the lungs.
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