Prospective Clinical Trial Evaluating Metronomic Chemotherapy in Patients With High-grade, Operable, Non-metastatic Osteosarcoma of the Extremity
Primary Purpose
High Grade Osteosarcoma
Status
Unknown status
Phase
Phase 2
Locations
Brazil
Study Type
Interventional
Intervention
continuous oral cyclophosphamide and methotrexate
Sponsored by
About this trial
This is an interventional treatment trial for High Grade Osteosarcoma focused on measuring of the extremity
Eligibility Criteria
Inclusion Criteria:
- Patients with high-grade malignancy osteosarcoma , biopsy-proven , newly diagnosed , previously untreated . Patients with osteosarcoma as a second malignancy should also be eligible .
- Patients with any primary site , with or without metastases at diagnosis , will be accepted and treated.
- Patients < 30 years.
- Patients must have normal body function and adequate renal function defined as serum creatinine < 1.5 x the normal value or creatinine clearance > 60ml/min/1 ,73m2 .
- Patients must have adequate hepatic function, defined as total bilirubin < 1.5 x normal, aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) < 2.5 x normal.
- Patients must have adequate cardiac function defined by a shortening fraction > 27 % by echocardiogram or ejection fraction > 47 % by radioisotopic angiogram .
If pre- chemotherapy amputation is necessary, the patient is included in the study and eligible to survival analyzes, however the pathological analyze response will be not performed.
Obtain material for pathological and molecular study is recommended .
- Whenever possible a central catheter should be placed against the intensity of chemotherapy and need for forced hydration .
- Patient or legal guardian must sign a consent form which will be explain the type of treatment and procedures that the patient will be submitted .
- Time > than 4 weeks between biopsy and initiation of treatment - Restaging
Exclusion Criteria:
- Disease progression ( increase of at least 20% of the extent of the lesion, taking as reference the smallest measurement recorded from the start of treatment, or the appearance of one or more lesions );
- Any properly documented clinical situation , which at the discretion of the attending physician , patient can not follow with chemotherapy , for safety reasons ;
- The evaluation of cardiac aspects will be done carefully , so will exclude patients with 20% reduction in the ejection fraction of the left ventricle compared to baseline or with a ventricular ejection fraction < 45 % regardless of baseline;
- The patient refusal to continue treatment ;
- Nephrotoxicity , neurotoxicity and ototoxicity grade 4 ;
- Delay greater than 40 days for the realization of the next treatment cycle , not related to toxicity;
- Refusal of surgery ; 8 . Variation above 20% of the recommended dose without justification.
Sites / Locations
- GRAACC- Institute of Pediatric OncologyRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Maintenance therapy
Control
Arm Description
73 weeks of continuous oral low dose chemotherapy with cyclophosphamide (CPM) and methotrexate (MTX) following 31 weeks of MAP.
31 weeks of MAP.
Outcomes
Primary Outcome Measures
Event-Free Survival
AT 5 YEARS
Secondary Outcome Measures
Overall survival
AT 5 YEARS
Full Information
NCT ID
NCT02273583
First Posted
July 7, 2014
Last Updated
February 10, 2016
Sponsor
Grupo de Apoio ao Adolescente e a Crianca com Cancer
1. Study Identification
Unique Protocol Identification Number
NCT02273583
Brief Title
Prospective Clinical Trial Evaluating Metronomic Chemotherapy in Patients With High-grade, Operable, Non-metastatic Osteosarcoma of the Extremity
Study Type
Interventional
2. Study Status
Record Verification Date
February 2016
Overall Recruitment Status
Unknown status
Study Start Date
May 2006 (undefined)
Primary Completion Date
June 2013 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Grupo de Apoio ao Adolescente e a Crianca com Cancer
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Preclinical models show that a daily antiangiogenic regimen at low-dose may be effective against chemotherapy-resistant tumors. The aim of this study is to evaluate the efficacy of maintenance therapy with continuous oral cyclophosphamide and methotrexate in patients with high grade, operable, non-metastatic osteosarcoma (OST) of the extremities. The primary end point is event-free survival (EFS) from randomization.
Detailed Description
The study design includes a backbone of 10 weeks of preoperative therapy using MAP (High-dose methotrexate, cisplatin, and doxorubicin). Following surgery, non-metastatic patients were randomized by blocks to complete 31 weeks of MAP or to receive 73 weeks of maintenance therapy following MAP; while metastatic patients received maintenance therapy in combination with MAP since the beginning of treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
High Grade Osteosarcoma
Keywords
of the extremity
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
738 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Maintenance therapy
Arm Type
Experimental
Arm Description
73 weeks of continuous oral low dose chemotherapy with cyclophosphamide (CPM) and methotrexate (MTX) following 31 weeks of MAP.
Arm Title
Control
Arm Type
No Intervention
Arm Description
31 weeks of MAP.
Intervention Type
Drug
Intervention Name(s)
continuous oral cyclophosphamide and methotrexate
Primary Outcome Measure Information:
Title
Event-Free Survival
Description
AT 5 YEARS
Time Frame
EFS AT 5 YEARS
Secondary Outcome Measure Information:
Title
Overall survival
Description
AT 5 YEARS
Time Frame
OS AT 5 YEARS
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Day
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with high-grade malignancy osteosarcoma , biopsy-proven , newly diagnosed , previously untreated . Patients with osteosarcoma as a second malignancy should also be eligible .
Patients with any primary site , with or without metastases at diagnosis , will be accepted and treated.
Patients < 30 years.
Patients must have normal body function and adequate renal function defined as serum creatinine < 1.5 x the normal value or creatinine clearance > 60ml/min/1 ,73m2 .
Patients must have adequate hepatic function, defined as total bilirubin < 1.5 x normal, aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) < 2.5 x normal.
Patients must have adequate cardiac function defined by a shortening fraction > 27 % by echocardiogram or ejection fraction > 47 % by radioisotopic angiogram .
If pre- chemotherapy amputation is necessary, the patient is included in the study and eligible to survival analyzes, however the pathological analyze response will be not performed.
Obtain material for pathological and molecular study is recommended .
Whenever possible a central catheter should be placed against the intensity of chemotherapy and need for forced hydration .
Patient or legal guardian must sign a consent form which will be explain the type of treatment and procedures that the patient will be submitted .
Time > than 4 weeks between biopsy and initiation of treatment - Restaging
Exclusion Criteria:
Disease progression ( increase of at least 20% of the extent of the lesion, taking as reference the smallest measurement recorded from the start of treatment, or the appearance of one or more lesions );
Any properly documented clinical situation , which at the discretion of the attending physician , patient can not follow with chemotherapy , for safety reasons ;
The evaluation of cardiac aspects will be done carefully , so will exclude patients with 20% reduction in the ejection fraction of the left ventricle compared to baseline or with a ventricular ejection fraction < 45 % regardless of baseline;
The patient refusal to continue treatment ;
Nephrotoxicity , neurotoxicity and ototoxicity grade 4 ;
Delay greater than 40 days for the realization of the next treatment cycle , not related to toxicity;
Refusal of surgery ; 8 . Variation above 20% of the recommended dose without justification.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sérgio Antônio Petrilli, MD
Phone
55-11-5080-8494
Email
sergiopetrilli@graacc.org.br
Facility Information:
Facility Name
GRAACC- Institute of Pediatric Oncology
City
São Paulo
State/Province
SP
ZIP/Postal Code
04023-062
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antônio Sérgio Petrilli, MD
Phone
55-11-5080-8494
Email
sergiopetrilli@graacc.org.br
First Name & Middle Initial & Last Name & Degree
Antônio Sérgio Petrilli, MD
12. IPD Sharing Statement
Learn more about this trial
Prospective Clinical Trial Evaluating Metronomic Chemotherapy in Patients With High-grade, Operable, Non-metastatic Osteosarcoma of the Extremity
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