Combined Chemotherapy With or Without Zoledronic Acid for Patients With Osteosarcoma
- Conditions
- Sarcoma
- Interventions
- Procedure: conventional surgery
- Registration Number
- NCT00470223
- Lead Sponsor
- UNICANCER
- Brief Summary
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Zoledronic acid may stop the growth of tumor cells in bone. Giving chemotherapy with or without zoledronic acid before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery. It is not yet known whether giving combination chemotherapy together with zoledronic acid is more effective than combination chemotherapy alone in treating osteosarcoma.
PURPOSE: This randomized phase III trial is studying combination chemotherapy and zoledronic acid to see how well they work compared with combination chemotherapy alone in treating patients with osteosarcoma.
- Detailed Description
OBJECTIVES:
Primary
* Compare the progression-free survival of patients with osteosarcoma treated with combination chemotherapy with or without zoledronic acid.
Secondary
* Compare the overall survival of patients treated with these regimens.
* Compare the percentage of patients with a good histologic response.
* Compare the long and short term toxicity of these regimens in these patients.
* Compare the quality of life of patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (\< 18 years vs 18-25 years vs \> 25 years), risk group (nonmetastatic or resectable vs metastatic or unresectable), and treatment center. Patients receive either methotrexate-based chemotherapy or doxorubicin hydrochloride-based chemotherapy according to age.
* Methotrexate-based chemotherapy (patients ≤ 25 years of age): Patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients receive methotrexate IV in weeks 1-3, 7, 8, 12, and 13 and etoposide IV and ifosfamide IV in weeks 4 and 9.
* Arm II: Patients receive methotrexate, etoposide, and ifosfamide as in arm I. Patients also receive zoledronic acid IV in weeks 1, 5, 9, and 13.
All patients undergo surgery in week 14. After surgery, patients are assigned to 1 of 2 groups for further treatment, based on histological response.
* Good responders (\< 10% viable cells): Patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients receive methotrexate IV in weeks 1-3, 7-9, 13-15, and 19-21 and etoposide IV in weeks 4 and 10. Patients also receive ifosfamide IV in weeks 4, 10, and 16.
* Arm II: Patients receive methotrexate, etoposide, and ifosfamide as in arm I. Patients also receive zoledronic acid IV in weeks 3, 7, 11, 15, 19, and 23.
* Bad responders (\> 10% viable cells): Patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients receive methotrexate IV in weeks 1, 5, 9, 13, and 17 and doxorubicin hydrochloride IV and cisplatin IV in weeks 2, 6, 10, 14, and 18.
* Arm II: Patients receive methotrexate, doxorubicin hydrochloride, and cisplatin as in arm I. Patients also receive zoledronic acid IV as in arm II (good responders).
* Doxorubicin hydrochloride-based chemotherapy (patients ≥ 18 years of age): Patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients receive doxorubicin hydrochloride IV and ifosfamide hydrochloride IV in weeks 1, 4, 7, 10, and 13 and cisplatin IV in weeks 1, 7, and 13.
* Arm II: Patients receive doxorubicin hydrochloride, ifosfamide, and cisplatin as in arm I. Patients also receive zoledronic acid IV in weeks 1, 5, 9, and 13.
All patients undergo surgery in week 16. After surgery, patients are assigned to 1 of 2 groups for further treatment, based on histological response.
* Good responders (\< 10% viable cells): Patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients receive doxorubicin hydrochloride IV in weeks 1 and 7 and ifosfamide IV in weeks 1, 4, 7, and 10.
* Arm II: Patients receive doxorubicin hydrochloride and ifosfamide as in arm I. Patients also receive zoledronic acid IV in weeks 1, 5, 9, 13, 17, and 21.
* Bad responders (\> 10% viable cells):
* Arm I: Patients receive etoposide IV and ifosfamide IV in weeks 1, 4, 7, 10, and 13.
* Arm II: Patients receive etoposide and ifosfamide as in arm I. Patients also receive zoledronic acid as in arm II (good responders).
PROJECTED ACCRUAL: A total of 440 patients will be accrued for this study.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 318
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Chemotherapy + zoledronic acid conventional surgery - chemotherapy conventional surgery - Chemotherapy + zoledronic acid zoledronic acid - chemotherapy cisplatin - Chemotherapy + zoledronic acid doxorubicin hydrochloride - Chemotherapy + zoledronic acid etoposide - Chemotherapy + zoledronic acid ifosfamide - Chemotherapy + zoledronic acid cisplatin - Chemotherapy + zoledronic acid methotrexate - chemotherapy ifosfamide - chemotherapy doxorubicin hydrochloride - chemotherapy etoposide - chemotherapy methotrexate -
- Primary Outcome Measures
Name Time Method Event-free survival 3 years
- Secondary Outcome Measures
Name Time Method Overall survival 10 years Percentage of good responders at the time of the surgery Short term and long term toxicity 10 years
Trial Locations
- Locations (37)
Centre Jean Perrin
🇫🇷Clermont-Ferrand, France
CHR de Besancon - Hopital Saint-Jacques
🇫🇷Besancon, France
CHU Hopital A. Morvan
🇫🇷Brest, France
Institut Gustave Roussy
🇫🇷Angers, France
CHU de la Timone
🇫🇷Marseille, France
Hopital d'Enfants de la Timone
🇫🇷Marseille, France
Centre Leon Berard
🇫🇷Lyon, France
Centre Paul Papin
🇫🇷Angers, France
Centre de Lutte Contre le Cancer Georges-Francois Leclerc
🇫🇷Dijon, France
Centre Antoine Lacassagne
🇫🇷Nice, France
Hopital Edouard Herriot - Lyon
🇫🇷Lyon, France
Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz
🇫🇷Besancon, France
CHR Clermont Ferrand, Hotel Dieu
🇫🇷Clermont-Ferrand, France
CHU de Caen
🇫🇷Caen, France
Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
🇫🇷Marseille, France
CHU Nord
🇫🇷Marseille, France
Hopital de l'Archet CHU de Nice
🇫🇷Nice, France
Centre Hospitalier Universitaire de Dijon
🇫🇷Dijon, France
Centre Oscar Lambret
🇫🇷Lille, France
CHU de Grenoble - Hopital Michallon
🇫🇷Grenoble, France
Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
🇫🇷Montpellier, France
Centre Alexis Vautrin
🇫🇷Vandoeuvre-les-Nancy, France
Hopital Jean Bernard
🇫🇷Poitiers, France
Centre Eugene Marquis
🇫🇷Rennes, France
Hopitaux Universitaire de Strasbourg
🇫🇷Strasbourg, France
C.H. Bastien de Clocheville
🇫🇷Tours, France
Institut Curie Hopital
🇫🇷Paris, France
Hopital Charles Nicolle
🇫🇷Rouen, France
Institut de Cancerologie de la Loire
🇫🇷Saint Priest en Jarez, France
CHRU de Tours - Hopital Trousseau
🇫🇷Tours, France
Centre Henri Becquerel
🇫🇷Rouen, France
Institut Bergonie
🇫🇷Bordeaux, France
Centre Regional Francois Baclesse
🇫🇷Caen, France
Hopital Arnaud de Villeneuve
🇫🇷Montpellier, France
Centre Regional Rene Gauducheau
🇫🇷Saint-Herblain, France
Hopital Universitaire Hautepierre
🇫🇷Strasbourg, France
Hopital des Enfants
🇫🇷Toulouse, France