Combined Chemotherapy With or Without Zoledronic Acid for Patients With Osteosarcoma

NCT ID: NCT00470223

Last Updated: 2025-06-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

318 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-03-31

Study Completion Date

2026-12-31

Brief Summary

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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

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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.

Conditions

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Sarcoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Chemotherapy + zoledronic acid

Group Type EXPERIMENTAL

cisplatin

Intervention Type DRUG

doxorubicin hydrochloride

Intervention Type DRUG

etoposide

Intervention Type DRUG

ifosfamide

Intervention Type DRUG

methotrexate

Intervention Type DRUG

zoledronic acid

Intervention Type DRUG

conventional surgery

Intervention Type PROCEDURE

chemotherapy

Group Type ACTIVE_COMPARATOR

cisplatin

Intervention Type DRUG

doxorubicin hydrochloride

Intervention Type DRUG

etoposide

Intervention Type DRUG

ifosfamide

Intervention Type DRUG

methotrexate

Intervention Type DRUG

conventional surgery

Intervention Type PROCEDURE

Interventions

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cisplatin

Intervention Type DRUG

doxorubicin hydrochloride

Intervention Type DRUG

etoposide

Intervention Type DRUG

ifosfamide

Intervention Type DRUG

methotrexate

Intervention Type DRUG

zoledronic acid

Intervention Type DRUG

conventional surgery

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

5 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis

INDUSTRY

Sponsor Role collaborator

Chugai Pharmaceutical

INDUSTRY

Sponsor Role collaborator

National Cancer Institute, France

OTHER_GOV

Sponsor Role collaborator

SFCE

UNKNOWN

Sponsor Role collaborator

Ligue contre le cancer, France

OTHER

Sponsor Role collaborator

UNICANCER

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Laurence Brugieres, MD

Role: STUDY_CHAIR

Gustave Roussy, Cancer Campus, Grand Paris

Locations

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Centre Paul Papin

Angers, , France

Site Status

Institut Gustave Roussy

Angers, , France

Site Status

Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz

Besançon, , France

Site Status

CHR de Besancon - Hopital Saint-Jacques

Besançon, , France

Site Status

Institut Bergonie

Bordeaux, , France

Site Status

CHU Hopital A. Morvan

Brest, , France

Site Status

CHU de Caen

Caen, , France

Site Status

Centre Regional Francois Baclesse

Caen, , France

Site Status

CHR Clermont Ferrand, Hotel Dieu

Clermont-Ferrand, , France

Site Status

Centre Jean Perrin

Clermont-Ferrand, , France

Site Status

Centre de Lutte Contre le Cancer Georges-Francois Leclerc

Dijon, , France

Site Status

Centre Hospitalier Universitaire de Dijon

Dijon, , France

Site Status

CHU de Grenoble - Hopital Michallon

Grenoble, , France

Site Status

Centre Oscar Lambret

Lille, , France

Site Status

Centre Leon Berard

Lyon, , France

Site Status

Hopital Edouard Herriot - Lyon

Lyon, , France

Site Status

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

Marseille, , France

Site Status

CHU de la Timone

Marseille, , France

Site Status

Hopital d'Enfants de la Timone

Marseille, , France

Site Status

CHU Nord

Marseille, , France

Site Status

Hopital Arnaud de Villeneuve

Montpellier, , France

Site Status

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

Montpellier, , France

Site Status

Centre Antoine Lacassagne

Nice, , France

Site Status

Hopital de l'Archet CHU de Nice

Nice, , France

Site Status

Institut Curie Hopital

Paris, , France

Site Status

Hopital Jean Bernard

Poitiers, , France

Site Status

Centre Eugene Marquis

Rennes, , France

Site Status

Hopital Charles Nicolle

Rouen, , France

Site Status

Centre Henri Becquerel

Rouen, , France

Site Status

Centre Regional Rene Gauducheau

Saint-Herblain, , France

Site Status

Institut de Cancerologie de la Loire

Saint-Priest-en-Jarez, , France

Site Status

Hopitaux Universitaire de Strasbourg

Strasbourg, , France

Site Status

Hopital Universitaire Hautepierre

Strasbourg, , France

Site Status

Hopital des Enfants

Toulouse, , France

Site Status

C.H. Bastien de Clocheville

Tours, , France

Site Status

CHRU de Tours - Hopital Trousseau

Tours, , France

Site Status

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, , France

Site Status

Countries

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France

References

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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.

Reference Type DERIVED
PMID: 31401903 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29791011 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28619014 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27324280 (View on PubMed)

Other Identifiers

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UNICANCER-SARCOME-09-0603

Identifier Type: OTHER

Identifier Source: secondary_id

2006-003377-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Sarcome 09/0603

Identifier Type: -

Identifier Source: org_study_id

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