Single Arm Phase 2 Study to Verify the Efficacy and safety of THP-based therapy for High-grade osteosarcoma of Extremity, rib, and sternum in pediatric and AYA patients to Reduce Toxicity (SAVE HEART)
NCCH2404 trial (SAVE HEART trial)
Arakawa Ayumu
National Cancer Center Hospital
5-1-1, Tsukiji, Chuo-ku, Tokyo 1040045, Japan
+81-3-3542-2511
aarakawa@ncc.go.jp
Miyazaki Bunpei
National Cancer Center Hospital
5-1-1, Tsukiji, Chuo-ku, Tokyo 1040045, Japan
+81-3-3542-2511
bmiyazak@ncc.go.jp
Recruiting
Mar. 06, 2025
55
Interventional
single arm study
open(masking not used)
no treatment control/standard of care control
single assignment
treatment purpose
1) Patients diagnosed with high-grade osteosarcoma based on the images of the primary tumor and the histopathological diagnosis of the tumor material obtained via biopsy. The histological classification should be according to the 4th edition of the Japanese Code of Medical Practice for Malignant Bone Tumors. Regardless of when, biopsy should be performed prior to registration. However, if biopsy was performed in another hospital, the pathological diagnosis must be made by a pathologist at the medical institution where the clinical trial is conducted by ordering a pathological specimen.
2) Patients with a primary lesion located in the upper limb including the upper limb girdle, the lower limb including the lower limb girdle, the sternum, and the ribs. However, patients with primary lesions in the lower limb girdle extending beyond the sacroiliac joint to the sacrum are not eligible.
3) Patients with resectable primary lesion
4) Patients with lesions classified as clinical stage IIA, IIB, or III according to the 8th edition of the Union for International Cancer Control TNM classification. For patients with a primary lesion located in the pelvic region, clinical staging should be conducted in accordance with the 7th edition.
5) Patients aged <=40 years upon enrollment
6) Patients with an Eastern Cooperative Oncology Group-performance status score of 0 or 1 and those without local symptoms such as bone fractures
7) Patients without a history of osteosarcoma and those with low- or high-grade lesions regardless of the site of origin
8) Patients without a history of chemotherapy or radiation therapy including treatment for other types of cancer.
9) Patients without any of the following:
(1) Signs fulfilling the definition of Li-Fraumeni syndrome
(2) History of retinoblastoma
10) Patients who underwent laboratory tests performed within 14 days prior to the date of enrollment (the same day of the week 2 weeks prior to the date of enrollment is acceptable) and who meet the following criteria:
(1) White blood cell count >= 3,000/mm3
(2) Neutrophil count >= 1,500/mm3
(3) Platelet count >= 100,000/mm3
(4) Hemoglobin level >= 8.0 g/dL
(5) AST level <= 100 U/L
(6) ALT level <= 100 U/L
(7) Total bilirubin level <= 1.5 mg/dL
(8) Creatinine level <= 1.2 mg/dL (serum creatinine level <= 0.8 mg/dL for patients aged <= 10 years)
(9) Creatinine clearance >= 70 mL/min
11) Patients with normal results on the most recent 12-lead resting ECG performed within 28 days of enrollment (the same day of the week 4 weeks prior to enrollment is acceptable) or those without grade 2 or higher abnormality based on the Common Terminology Criteria for Adverse Events version 5.0.
12) Patients with a left ventricular ejection fraction (LVEF) of >= 60% on the last transthoracic echocardiogram conducted within 28 days prior to enrollment (same day of the week 4 weeks prior to enrollment is acceptable).
13) Written informed consent to participate in the study is obtained from patients aged >=16 years. If the patient is a minor aged >=16 years, written informed consent is obtained from the patients and their surrogates.
1) Patients with complex diabetes mellitus that is being treated with continuous insulin use or those with poorly controlled glucose levels (HbA1c level >= 6.5%)
2) Patients with uncontrolled hypertension
3) Patients with a history of myocardial infarction or unstable angina pectoris
4) Patients with a cardiac pacemaker
5) Patients with an infectious disease requiring systemic treatment
6) Patients with fever (> 38 degrees Celsius, not including tumor fever that can be ruled out as infection)
7) Patients with multiple active cancers (synchronous multiple cancers and iatrogenic multiple cancers with a disease-free interval of <= 5 years). However, carcinoma in situ (intraepithelial carcinoma) and intramucosal carcinoma equivalent lesions that can be cured with local treatment are not classified as active multiple cancers.
8) Pregnant, potentially pregnant, or lactating women
9) Patients with psychiatric disorders or psychiatric symptoms that could interfere with participation in this study
10) Patients receiving continuous systemic administration of steroids (oral or intravenous)
11) Patients who tested positive for HBs antigen, HBc antibody, or HBs antibody. However, they may be enrolled if only HBs antibody is present and there is a documented history of hepatitis B vaccination or the HBV-DNA quantification is less than the detection sensitivity)
12) Patients who tested positive for HIV antibody, HTLV-1 antibody, or HCV antibody. Patients with positive HCV antibodies but without detectable HCV-RNA should be excluded. All of these must be confirmed via blood test.
No limit
40age old under
Both
Primary localized high-grade osteosarcoma of extremities, ribs, and sternum in the pediatric and AYA
Neoadjuvant and adjuvant chemotherapy regimen (MTP therapy) comprising three drugs (methotrexate [M], pirarubicin [THP-Adriamycin, THP, T], and cisplatin [CDDP, P]) and surgery.
osteosarcoma in pediatric and AYA
pediatric, AYA, pirarubicin
Osteosarcoma
3-Year disease-free survival
3-Year relapse-free survival
3-Year overall survival
Ratio of standard responders
Presurgical progression ratio
3-Year disease-free survival rate in each histological response group
Incidence rate of drug-induced cardiac dysfunction
Treatment-related mortality rate
Incidence rate of other adverse events
Japan Agency for Medical Research and Development
National Cancer Center Hospital Certified Review Board
