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

NCT05057130 | Recruiting Phase 2

• 1 other identifier: AMAP2021-7-2
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Osteosarcoma; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma; Sarcoma of Bone

Keywords

Bone sarcoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Proportion of patients who have a partial or complete response to therapy

  6 months

Secondary Outcomes (2)

• Comparison of tumor necrosis

  6 months

• Comparison of safety assessment

  6 months

Study Arms (2)

Three-component chemotherapy

EXPERIMENTAL

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

Drug: Doxorubicin, Cisplatin, Methotrexate

Two-component chemotherapy

ACTIVE COMPARATOR

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. The interval between cycles is 28 days

Drug: Doxorubicin, Cisplatin

Interventions

Doxorubicin, Cisplatin, Methotrexate DRUG

IV

Also known as: MAP

Three-component chemotherapy

Doxorubicin, Cisplatin DRUG

IV

Also known as: AP

Two-component chemotherapy

Eligibility Criteria

• Age: 24 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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 cell sarcoma, 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, prostate cancer
• Clinically significant cardiovascular or cerebrovascular diseases within the last 6 months (acute myocardial infarction, unstable angina pectoris, significant ventricular arrhythmias, severe heart failure (NYHA class IV), stroke or uncontrolled arterial hypertension)
• Renal failure (serum creatinine level more than 150 μmol / L), except for cases caused by lymphoid infiltration of the kidneys, and tumor disintegration syndrome
• Hepatic failure (except for cases caused by leukemic / lymphoid organ infiltration), acute hepatitis (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) or acute infectious diseases
• Brain metastases
• Life-threatening conditions (bleeding, tumor decay, etc.)
• Hypersensitivity to the active substance of the investigational drugs or any of the auxiliary components or their intolerance
• Surgical interventions less than 21 days before starting therapy

Sponsors & Collaborators

• Blokhin's Russian Cancer Research Center: lead

Study Sites (1)

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

Moscow, 115478, Russia

RECRUITING

Related Links

• official site
• russian surcoma group site

MeSH Terms

Conditions

Osteosarcoma; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma; Bone Neoplasms

Interventions

Doxorubicin; Cisplatin; Methotrexate

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms by Histologic Type; Neoplasms; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Neoplasms by Site; Bone Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Beniamin Bokhyan, PhD

  N.N. Blokhin NMRCO

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anastasia Tararykova

CONTACT

+79175274287; anastasiatararykova@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2021
• First Posted: September 27, 2021
• Study Start: January 10, 2022
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: April 1, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)