Neoadjuvant Combination of Doxorubicin, Cisplatin and Methotrexate in Patients Aged 24-40 Years With Primary Bone Tumors

Last updated: March 29, 2024
Sponsor: Blokhin's Russian Cancer Research Center
Overall Status: Active - Recruiting

Phase

2/3

Condition

Neoplasms

Sarcoma

Osteosarcoma

Treatment

Doxorubicin, Cisplatin

Doxorubicin, Cisplatin, Methotrexate

Clinical Study ID

NCT05057130
AMAP2021-7-2
  • Ages 24-40
  • All Genders

Study Summary

Two cycles of neoadjuvant three-component chemotherapy according to the MAP prototoc: Doxorubicin 25 mg / m2 IV on days 1-3, Cisplatin 120 mg / m2 IV on day 1 against the background of hyperhydration. G-CSF support from 4 to 13 days. Methotrexate 12 g / m2 at 28 and 35 days IV with leucovorin 60 mg / m2 in the first 5 days after each administration of methotrexate. The interval between cycles is 42 days.

The advantage of this regimen is to use the three-component chemotherapy regimen, which should increase the degree of tumor necrosis and increase the rate of tumor response to treatment, which will further improve the disease prognosis. Currently, the use of such treatment for adult patients (over 24 years old) is controversial. Since it is believed that the elimination of methotrexate in adult patients is more delayed than in patients under 24 years old, and can lead to serious adverse events (SAE). However, the use of modern standard methods of hemodialysis makes it possible to avoid SAE.

Eligibility Criteria

Inclusion

Inclusion Criteria: Histologically confirmed diagnosis of primary bone tumor (osteosarcoma) Age from 24 to 40 years Operable process, possibility of performing resection R0-R1 ECOG performance score 0 or 1 Normal renal function (estimated creatinine clearance more than 60 ml / min) Normal liver function (AST, ALT - no more than 3 norms) Left ventricular ejection fraction> 55% Adequate marrow function (hemoglobin level more than 9 g / dL, neutrophil count more than 1.5 thousand / μl, platelet number more than 100 thousand / μl) Signed informed consent

Exclusion

Exclusion Criteria: Children, women during pregnancy, childbirth, women during breastfeeding Persons with mental disorders The presence of an active viral infection with HIV, viral hepatitis B and C Inoperable tumor Morphologically confirmed diagnosis of GIST, Kaposi's sarcoma, alveolar or clear cellsarcoma, chondrosarcoma, chordoma, giant cell tumor, paraosal osteosarcoma, Ewing's sarcoma / PNET, rhabdomyosarcoma, G1 osteosarcoma The presence of a second malignant neoplasm within the last 5 years before enrollment,other than cured basal cell or squamous cell carcinoma or cervical cancer in situ, prostatecancer Clinically significant cardiovascular or cerebrovascular diseases within the last 6 months (acute myocardial infarction, unstable angina pectoris, significant ventriculararrhythmias, severe heart failure (NYHA class IV), stroke or uncontrolled arterialhypertension) Renal failure (serum creatinine level more than 150 μmol / L), except for cases caused bylymphoid infiltration of the kidneys, and tumor disintegration syndrome Hepatic failure (except for cases caused by leukemic / lymphoid organ infiltration), acutehepatitis (serum bilirubin level more than 2 norms, ALT and AST activity more than 4 norms,prothrombin index less than 50%) Decompensated diabetes mellitus (blood serum glucose above 15 mmol / L) Sepsis (septicopyemic foci, hemodynamic instability; ineffective antimicrobial therapy) oracute infectious diseases Brain metastases Life-threatening conditions (bleeding, tumor decay, etc.) Hypersensitivity to the active substance of the investigational drugs or any of theauxiliary components or their intolerance Surgical interventions less than 21 days before starting therapy

Study Design

Total Participants: 50
Treatment Group(s): 2
Primary Treatment: Doxorubicin, Cisplatin
Phase: 2/3
Study Start date:
January 10, 2022
Estimated Completion Date:
December 31, 2024

Study Description

The role of methotrexate in neoadjuvant chemotherapy for bone tumors is a topic for debate. However, the benefits of methotrexate have been confirmed in at least one phase II study showing better results with high doses of methotrexate in the context of triple chemotherapy. Moreover, many studies have shown a correlation between peak serum methotrexate levels, tumor response to chemotherapy, and treatment outcome. Thus, it is possible that the negative results of the effectiveness of methotrexate have been compromised due to the administration of insufficient doses or incorrect administration of the drug. The optimal regimen of methotrexate administration has not been established. However, the control group in the EURAMOS-1 study of the American Osteosarcoma Research Group (AOST) is considered as the standard. The main practical problem with the use of triple chemotherapy in a group of patients aged 24 and older is that the slow clearance of methotrexate can delay the administration of the next cycle of doxorubicin-cisplatin, thereby reducing the dose intensity and adversely affecting the outcome. Currently, there are both isolated clinical cases and observations of a small number of included patients. The use of three-component neoadjuvant chemotherapy for primary bone tumors will improve the rate of response to treatment, reduce the frequency of recurenses and disease progression.

Connect with a study center

  • Federal State Budgetary Institution "N.N. Blokhin National Medical Research Center of Oncology" оf the Ministry of Health of the Russian Federation

    Moscow, 115478
    Russian Federation

    Active - Recruiting

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