Combined Chemotherapy With or Without Zoledronic Acid for Patients With Osteosarcoma

NCT00470223 | Active Not Recruiting Phase 3 DMC

• 3 other identifiers: Sarcome 09/0603UNICANCER-SARCOME-09-06032006-003377-27
• Study Type: interventional
• Target: 318
• Locations: 1 country
• Sites: 37

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.

Conditions

Sarcoma

Keywords

localized osteosarcoma; metastatic osteosarcoma

Outcome Measures

Primary Outcomes (1)

• Event-free survival

  3 years

Secondary Outcomes (3)

• Overall survival

  10 years

• Percentage of good responders

  at the time of the surgery

• Short term and long term toxicity

  10 years

Study Arms (2)

Chemotherapy + zoledronic acid

EXPERIMENTAL

Drug: cisplatin; Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: ifosfamide; Drug: methotrexate; Drug: zoledronic acid; Procedure: conventional surgery

chemotherapy

ACTIVE COMPARATOR

Drug: cisplatin; Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: ifosfamide; Drug: methotrexate; Procedure: conventional surgery

Interventions

cisplatin DRUG

Chemotherapy + zoledronic acid; chemotherapy

doxorubicin hydrochloride DRUG

Chemotherapy + zoledronic acid; chemotherapy

etoposide DRUG

Chemotherapy + zoledronic acid; chemotherapy

ifosfamide DRUG

Chemotherapy + zoledronic acid; chemotherapy

methotrexate DRUG

Chemotherapy + zoledronic acid; chemotherapy

zoledronic acid DRUG

Chemotherapy + zoledronic acid

conventional surgery PROCEDURE

Chemotherapy + zoledronic acid; chemotherapy

Eligibility Criteria

• Age: 5 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Histologically confirmed high-grade osteosarcoma
• Bilirubin ≤ 2 times upper limit of normal
• No medical condition that would preclude study treatment
• Not pregnant or nursing
• Fertile patients must use effective contraception
• Shortening fraction ≥ 28%
• LVEF ≥ 50%
• Glomerular filtration rate ≥ 70mL/min
• No recent dental problem, including infection, traumatization, or surgery

You may not qualify if:

• Low-grade osteosarcoma
• Small cell osteosarcoma
• Maxillary osteosarcoma
• Primary resected osteosarcoma
• Osteosarcoma with multiple metastases for which complete removal is not feasible even after shrinkage with chemotherapy
• Extra-osseous osteosarcoma
• Any prior osteonecrosis of the maxilla
• No prior chemotherapy or radiotherapy

Sponsors & Collaborators

• UNICANCER: lead
• Novartis: collaborator
• Chugai Pharmaceutical: collaborator
• National Cancer Institute, France: collaborator
• SFCE: collaborator
• Ligue contre le cancer, France: collaborator

Study Sites (37)

Centre Paul Papin

Angers, 49036, France

Location

Institut Gustave Roussy

Angers, 49036, France

Location

Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz

Besançon, 25030, France

Location

CHR de Besancon - Hopital Saint-Jacques

Besançon, 25030, France

Location

Institut Bergonie

Bordeaux, 33076, France

Location

CHU Hopital A. Morvan

Brest, 29609, France

Location

CHU de Caen

Caen, 14033, France

Location

Centre Regional Francois Baclesse

Caen, 14076, France

Location

CHR Clermont Ferrand, Hotel Dieu

Clermont-Ferrand, 63003, France

Location

Centre Jean Perrin

Clermont-Ferrand, 63011, France

Location

Centre de Lutte Contre le Cancer Georges-Francois Leclerc

Dijon, 21079, France

Location

Centre Hospitalier Universitaire de Dijon

Dijon, 21079, France

Location

CHU de Grenoble - Hopital Michallon

Grenoble, 38043, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

Hopital Edouard Herriot - Lyon

Lyon, 69437, France

Location

Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes

Marseille, 13273, France

Location

CHU de la Timone

Marseille, 13385, France

Location

Hopital d'Enfants de la Timone

Marseille, 13385, France

Location

CHU Nord

Marseille, 13915, France

Location

Hopital Arnaud de Villeneuve

Montpellier, 34295, France

Location

Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle

Montpellier, 34298, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Hopital de l'Archet CHU de Nice

Nice, F-06202, France

Location

Institut Curie Hopital

Paris, 75248, France

Location

Hopital Jean Bernard

Poitiers, 86021, France

Location

Centre Eugene Marquis

Rennes, 35042, France

Location

Hopital Charles Nicolle

Rouen, 76031, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

Centre Regional Rene Gauducheau

Saint-Herblain, 44805, France

Location

Institut de Cancerologie de la Loire

Saint-Priest-en-Jarez, 42270, France

Location

Hopitaux Universitaire de Strasbourg

Strasbourg, 67091, France

Location

Hopital Universitaire Hautepierre

Strasbourg, 67098, France

Location

Hopital des Enfants

Toulouse, 31059, France

Location

C.H. Bastien de Clocheville

Tours, 3700, France

Location

CHRU de Tours - Hopital Trousseau

Tours, 37044, France

Location

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, 54511, France

Location

Related Publications (4)

• Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.

  PMID: 31401903 DERIVED

• Lui G, Treluyer JM, Fresneau B, Piperno-Neumann S, Gaspar N, Corradini N, Gentet JC, Marec Berard P, Laurence V, Schneider P, Entz-Werle N, Pacquement H, Millot F, Taque S, Freycon C, Lervat C, Le Deley MC, Mahier Ait Oukhatar C, Brugieres L, Le Teuff G, Bouazza N; Sarcoma Group of UNICANCER. A Pharmacokinetic and Pharmacogenetic Analysis of Osteosarcoma Patients Treated With High-Dose Methotrexate: Data From the OS2006/Sarcoma-09 Trial. J Clin Pharmacol. 2018 Dec;58(12):1541-1549. doi: 10.1002/jcph.1252. Epub 2018 May 23.

  PMID: 29791011 DERIVED

• Tabone MD, Brugieres L, Piperno-Neumann S, Selva MA, Marec-Berard P, Pacquement H, Lervat C, Corradini N, Gentet JC, Couderc R, Chevance A, Mahier-Ait Oukhatar C, Entz-Werle N, Blay JY, Le Deley MC. Prognostic impact of blood and urinary angiogenic factor levels at diagnosis and during treatment in patients with osteosarcoma: a prospective study. BMC Cancer. 2017 Jun 15;17(1):419. doi: 10.1186/s12885-017-3409-z.

  PMID: 28619014 DERIVED

• Piperno-Neumann S, Le Deley MC, Redini F, Pacquement H, Marec-Berard P, Petit P, Brisse H, Lervat C, Gentet JC, Entz-Werle N, Italiano A, Corradini N, Bompas E, Penel N, Tabone MD, Gomez-Brouchet A, Guinebretiere JM, Mascard E, Gouin F, Chevance A, Bonnet N, Blay JY, Brugieres L; Sarcoma Group of UNICANCER; French Society of Pediatric Oncology (SFCE); French Sarcoma Group (GSF-GETO). Zoledronate in combination with chemotherapy and surgery to treat osteosarcoma (OS2006): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol. 2016 Aug;17(8):1070-1080. doi: 10.1016/S1470-2045(16)30096-1. Epub 2016 Jun 17.

  PMID: 27324280 DERIVED

MeSH Terms

Conditions

Sarcoma; Osteosarcoma

Interventions

Cisplatin; Doxorubicin; Etoposide; Ifosfamide; Methotrexate; Zoledronic Acid

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Diphosphonates; Organophosphonates; Imidazoles; Azoles

Study Officials

• Laurence Brugieres, MD

  Gustave Roussy, Cancer Campus, Grand Paris

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2007
• First Posted: May 7, 2007
• Study Start: March 1, 2007
• Primary Completion: December 1, 2015
• Study Completion (Estimated): December 1, 2026
• Last Updated: June 8, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (37)