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

Primary Purpose

Osteosarcoma, Neoplasms, Connective Tissue, Neoplasms, Connective and Soft Tissue

Status

Recruiting

Phase

Phase 2

Locations

Russian Federation

Study Type

Interventional

Intervention

Doxorubicin, Cisplatin, Methotrexate

Doxorubicin, Cisplatin

About this trial

This is an interventional treatment trial for Osteosarcoma focused on measuring Bone sarcoma

Eligibility Criteria

24 Years - 40 Years (Adult)All SexesDoes not accept healthy volunteers

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 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 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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Three-component chemotherapy

Two-component chemotherapy

Arm Description

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

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

Outcomes

Primary Outcome Measures

Overall Response Rate

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

Secondary Outcome Measures

Comparison of tumor necrosis

Proportion of tumor necrosis after chemotherapy

Comparison of safety assessment

Adverse Event Assessment and Serious Adverse Event Assessment according to CTCAE 5.0

Full Information

NCT ID

NCT05057130

First Posted

September 7, 2021

Last Updated

March 1, 2022

Sponsor

Blokhin's Russian Cancer Research Center

1. Study Identification

Unique Protocol Identification Number

NCT05057130

Brief Title

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

Official Title

Neoadjuvant Three-component Chemotherapy Based on a Combination of Doxorubicin, Cisplatin and Methotrexate in Patients Aged 24-40 Years With Primary Bone Tumors to Increase the Response Rate Compared With Two-component Chemotherapy

Study Type

Interventional

2. Study Status

Record Verification Date

March 2022

Overall Recruitment Status

Recruiting

Study Start Date

January 10, 2022 (Actual)

Primary Completion Date

December 2024 (Anticipated)

Study Completion Date

December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Blokhin's Russian Cancer Research Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

Bone sarcoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Three-component chemotherapy

Arm Type

Experimental

Arm Description

Arm Title

Two-component chemotherapy

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Doxorubicin, Cisplatin, Methotrexate

Other Intervention Name(s)

MAP

Intervention Description

Intervention Type

Drug

Intervention Name(s)

Doxorubicin, Cisplatin

Other Intervention Name(s)

Intervention Description

Primary Outcome Measure Information:

Title

Overall Response Rate

Description

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

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Comparison of tumor necrosis

Description

Proportion of tumor necrosis after chemotherapy

Time Frame

6 months

Title

Comparison of safety assessment

Description

Adverse Event Assessment and Serious Adverse Event Assessment according to CTCAE 5.0

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

24 Years

Maximum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

Eligibility Criteria

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 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 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Anastasia Tararykova

Phone

+79175274287

anastasiatararykova@gmail.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Beniamin Bokhyan, PhD

Organizational Affiliation

N.N. Blokhin NMRCO

Official's Role

Principal Investigator

Facility Information:

Facility Name

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

City

Moscow

ZIP/Postal Code

115478

Country

Russian Federation

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Anastasia Tararykova

Phone

89175274287

anastasiatararykova@gmail.com

First Name & Middle Initial & Last Name & Degree

Anastasia Tararykova

First Name & Middle Initial & Last Name & Degree

Andrei Konev

First Name & Middle Initial & Last Name & Degree

Beniamin Bokhyan, PhD

First Name & Middle Initial & Last Name & Degree

Aslan Valiev, PhD

12. IPD Sharing Statement

Plan to Share IPD

Links:

URL

https://www.ronc.ru/about/struktura/niiko/ooo/hn1/

Description

official site

URL

https://sarcomarus.ru/

Description

russian surcoma group site

Learn more about this trial

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

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