Prospective Clinical Trial Evaluating Metronomic Chemotherapy in Patients With High-grade, Operable, Non-metastatic Osteosarcoma of the Extremity

NCT ID: NCT02273583

Last Updated: 2016-02-11

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 738 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-05-31

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.

Conditions

High Grade Osteosarcoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Maintenance therapy

73 weeks of continuous oral low dose chemotherapy with cyclophosphamide (CPM) and methotrexate (MTX) following 31 weeks of MAP.

Group Type: EXPERIMENTAL

continuous oral cyclophosphamide and methotrexate

Intervention Type: DRUG

Control

31 weeks of MAP.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

continuous oral cyclophosphamide and methotrexate

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patients with high-grade malignancy osteosarcoma , biopsy-proven , newly diagnosed , previously untreated . Patients with osteosarcoma as a second malignancy should also be eligible .

2. Patients with any primary site , with or without metastases at diagnosis , will be accepted and treated.

3. Patients < 30 years.

4. 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 .

5. 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.

6. Patients must have adequate cardiac function defined by a shortening fraction > 27 % by echocardiogram or ejection fraction > 47 % by radioisotopic angiogram .

7. 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 .

8. Whenever possible a central catheter should be placed against the intensity of chemotherapy and need for forced hydration .

9. 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 .

10. Time > than 4 weeks between biopsy and initiation of treatment - Restaging

Exclusion Criteria

1. 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 );

2. Any properly documented clinical situation , which at the discretion of the attending physician , patient can not follow with chemotherapy , for safety reasons ;

3. 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;

4. The patient refusal to continue treatment ;

5. Nephrotoxicity , neurotoxicity and ototoxicity grade 4 ;

6. Delay greater than 40 days for the realization of the next treatment cycle , not related to toxicity;

7. Refusal of surgery ; 8 . Variation above 20% of the recommended dose without justification.

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Grupo de Apoio ao Adolescente e a Crianca com Cancer

OTHER

Sponsor Role: lead

Responsible Party

Antônio Sérgio Petrilli

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

GRAACC- Institute of Pediatric Oncology

São Paulo, São Paulo, Brazil

Site Status: RECRUITING

Countries

Brazil

Central Contacts

Sérgio Antônio Petrilli, MD

Role: CONTACT

sergiopetrilli@graacc.org.br

55-11-5080-8494

Facility Contacts

Antônio Sérgio Petrilli, MD

Role: primary

sergiopetrilli@graacc.org.br

55-11-5080-8494

Other Identifiers

GLATO 2006

Identifier Type: -

Identifier Source: org_study_id