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OsteosarcomaPhase 2OSII-TTPNCT00978471

Adjuvant High-Dose Thiotepa and Stem Cell Rescue Associated With Conventional Chemotherapy in Relapsed Osteosarcoma

A Phase 2 study testing Thiotepa in people with Osteosarcoma, run by Centre Leon Berard at 23 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Approximately 150 new cases of osteosarcoma are reported each year in France, of which 15 to 20% are metastatic. Further to the initial standard care, about 45% of the patients relapse within a median duration of 20 months. Read more about this study

Who is it for?
Ages 1 year to 50 years
Conditions the study is for
Osteosarcoma
What is being tested?
Thiotepa
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
23 sitesFrance
Study dates
Jul 2009to 29 Oct 2018
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 50 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Age > 1 year and < 50 years
  • First osteosarcoma relapse, either local or metastatic, or second relapse after exclusive surgery NB: Whenever possible, only patients with histological evidence of relapse will be included.
  • Indication for chemotherapy confirmed by a multidisciplinary committee.
  • Surgical resection of all tumor sites must be possible, either as first-line therapy or after chemotherapy.
  • Lansky score ≥ 60%, or ECOG Performance Status ≤ 2
  • ≥ 21-day interval after first-line chemotherapy
Show all 14Show fewer
  • Blood tests, renal and liver functions within the normal range for age with, in particular, 7 days prior to study entry, blood or serum values as follows:
  • blood: neutrophil count > 1 G/L; platelets >100 G/L
  • renal: serum creatinine ≤ 1.5 x ULN depending on age; patients with serum creatinine values > 1.5 x ULN are eligible if creatinine clearance is > 70 mL/min/1.73 m²
  • liver: total bilirubin < 2 x ULN; ASAT and ALAT ≤ 5 x ULN
  • cardiac: isotopic or echographic Left Ventricular Ejection Fraction > 50 %.
  • Signed written informed consent; for children, signed consent from the patient (depending on age) and from the parents or legal representative is mandatory
  • Documented negative serum βHCG for female patients of childbearing age
  • Affiliation with health insurance.

Who cannot join

  • Patients with multiple relapses for whom surgical resection seems impossible, even after chemotherapy.
  • Patients already treated with high-dose chemotherapy regimens
  • Patients with a contra-indication to the treatment proposed
  • Patients not eligible for leukapheresis
  • Two-year follow-up impossible due to social, family, geographic or psychological reasons
  • Patient included in another protocol of clinical research
  • Pregnant or lactating women.

Trial locations and contacts

23 sites in 1 country.

23 sites in 1 country

France23 sites

  • CHU Besançon- Hôpital Jean Minjoz

    Besançon, 25000

  • Chu - Hopital Des Enfants Bordeaux

    Bordeaux, 33000

  • CHU Dijon Le Bocage, Hôpital d'Enfants

    Dijon, 21079

  • Chu Grenoble

    Grenoble, 38045

  • Centre Oscar Lambret

    Lille, 59000

  • Centre Léon Bérard - Institut d'Hémato-Oncologie Pediatrique

    Lyon, 69373

  • Institut Paoli Calmettes

    Marseille, 13273

  • Hôpital des Enfants de la Timone

    Marseille, 13385

  • Chu Nantes - Hopital Meres Et Enfants

    Nantes, 44093

  • Centre Antoine Lacassagne

    Nice, 06189

  • CHU Nice, Hôpital L'Archet 2

    Nice, 06202

  • Institut Curie

    Paris, 75248

  • Hopital D'Enfants Armand Trousseau

    Paris, 75571

  • CHU Poitiers, site de la Milétrie

    Poitiers, 86021

  • CHU RENNES - Hôpital Sud

    Rennes, 35023

  • Chu La Reunion

    Saint-Denis, 97405

  • Institut de Cancérologie de l'Ouest - René Gauducheau

    Saint-Herblain, 44805

  • CHU de SAINT-ETIENNE, Hôpital Nord

    Saint-Priest-en-Jarez, 42270

  • Institut Lucien Neurwith

    Saint-Priest-en-Jarez, 42270

  • Hopital de Hautepierre

    Strasbourg, 67098

  • Chu Toulouse - Hopital D'Enfants

    Toulouse, 31059

  • Chu Nancy - Hopital D'Enfants

    Vandœuvre-lès-Nancy, 54511

  • Institut Gustave Roussy

    Villejuif, 95805

Other trials in France

About this study

Official title: Efficacy and Tolerance Adjuvant High-Dose Thiotepa With Peripheral Stem Cell Rescue Associated With Conventional Chemotherapy in Children and Adults With Relapsed Osteosarcoma

Approximately 150 new cases of osteosarcoma are reported each year in France, of which 15 to 20% are metastatic.

Further to the initial standard care, about 45% of the patients relapse within a median duration of 20 months.

Read more

Result of the OS94 study results and of the investigation performed within the CRLCC, indicate that 25 to 30 patients (children and adults) experience an osteosarcoma relapse each year in FRANCE.

According to several studies, the 5-year overall survival rate of patients in first relapse is 23-28%,with a median post relapse survival of 10 to 17 months. Multiple relapse cases are also reported in the COSS study, with a median time to second relapse of 0.8 year.

At present, there is no reference treatment for the standard care of osteosarcoma relapse in FRANCE.

Thiotepa is known for its antitumor effect in numerous malignant tumors. In 2007, a study from our institution reported that about 35% of all osteosarcoma relapses are treated with a high-dose thiotepa while the efficacy and tolerance of this therapeutic strategy have never been assessed.

These results highlight the need to the evaluate the efficacy and tolerance of this high-dose of thiotepa within a clinical trial and its inclusion in the standard care of the osteosarcoma at relapse.

Read the detailed description

Despite the absence of tumor registry, approximately 150 new cases of osteosarcoma are reported each year in France (100 cases per year in children and 50 cases in adults), of which 15 to 20% are metastatic. The standardized impact rate in the world population is estimated at 3 per million inhabitants per year.

Further to the initial standard care, about 45% of the patients relapse within a median interval of 20 months (range 3 months - 10 years).

Results of the OS94 study and of the investigation performed within the CRLCC indicate that 25 to 30 patients (children and adults) experience an osteosarcoma relapse each year in FRANCE.

Results of the five major published series indicate that the 5-year overall survival rate of patients in first relapse is between 23 and 28%, with a median post-relapse survival of 10 to 17 months. Multiple relapse cases are also reported in the COSS study, with a median time to second relapse of 0.8 year.

At present, there is no reference treatment for the standard care of osteosarcoma relapse in FRANCE.

Some recommendations have been given in the OS94 protocol, but they are generally not followed or they are implemented in a heterogeneous manner.

Thiotepa (N N' N'' triethylenethiophosphoramide), an alkylating agent of the chemical family of ethylene-imines, is known for its antitumor effect in a number of malignant tumors.

Its efficacy in osteosarcoma has been reported in the literature. A retrospective study of the SFCE (French Society for Childhood Cancer, results not yet published) in 45 patients presenting with refractory osteosarcoma or relapse has shown a radiological reaction rate of 30%.

Moreover, a preliminary investigation performed by the CLB in 2007 within the framework of the SFCE study explored all relapse cases diagnosed between the beginning of 2004 and the end of 2006. Results showed that about 35% of the patients with osteosarcoma relapses are treated with high-dose thiotepa while the efficacy and tolerance of this therapeutic strategy have never been assessed.

Altogether, these results led the SFCE osteosarcoma group to propose the evaluation of the efficacy and tolerance of this high-dose thiotepa chemotherapy within a clinical trial and to include the drug in the standard care of osteosarcoma in relapse.

Conditions
Osteosarcoma
Being tested
Thiotepa
Keywords
Conventional chemotherapy, cytapheresis, Peripheral stem cell autograft, Surgical resection, Thiotepa
Medical subject headings
Osteosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ThiotepaDrug

    Also called N N'N'triethylenethiophosphosphoramide, Tepadina

    Thiotepa 8-12mg/m²/day/injection Total dose for one cure:15-50mg.

Study groups in NCT00978471
Study groupRoleWhat they receive
experimental arm thiotepaExperimental4 courses of conventional chemotherapy followed by high-dose Thiotepa with peripheral stem cell rescue. Surgical resection of all tumor masses will be performed as soon as possible.
Receives: Drug: Thiotepa
Reference armOther4 courses of conventional chemotherapy. Surgical resection of all tumor masses will be performed as soon as possible.
Receives: Drug: Thiotepa

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Estimate the overall survival rate

    Measured: 24 months

Secondary outcomes (6)

  1. Estimate overall survival after relapse diagnosis

    Measured: 24 months

  2. Estimate the survival free progression after randomization

    Measured: 24 months

  3. Evaluate the tolerance profile of experimental treatment (hematologic toxicity)

    Measured: every 3 weeks

  4. Estimate the rate of tumor response to treatment as assessed by conventional CT-scan

    Measured: at inclusion, day 14-day 21 after the 2nd chemotherapy cycle, before randomization, day 14-day 21 after the 4th chemotherapy cycle, after thiotepa cure and 8 weeks after the end of treatment

  5. Estimate histological response to treatment on surgical tumor samples

    Measured: If surgery is applicable, a few weeks after thiotepa cure (12 to 17 weeks after inclusion)

  6. Study of biological and genomic properties and analysis of angiogenic markers correlated with relapse (optional)

    Measured: At inclusion,at surgery , and at the end of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Sep 2009 (estimated)
  2. Study startJul 2009
  3. Primary completion29 Oct 2018
  4. Study completion29 Oct 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
44 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00978471
Sponsor's protocol ID
OSII-TTP
Other IDs
2009-009899-12, 2009
Acronym
OSII-TTP
Status last verified
Aug 2018
First submitted
16 Sep 2009
Last updated
17 May 2019
Results posted
No
Data monitoring committee
Yes

Publications

  • Desandes E, Lacour B, Sommelet D, Buemi A, Danzon A, Delafosse P, Grosclaude P, Mace-Lesech J, Raverdy-Bourdon N, Tretarre B, Velten M, Brugieres L. Cancer incidence among adolescents in France. Pediatr Blood Cancer. 2004 Dec;43(7):742-8. doi: 10.1002/pbc.20106.

    PubMed 15390305

  • Widhe B, Widhe T. Initial symptoms and clinical features in osteosarcoma and Ewing sarcoma. J Bone Joint Surg Am. 2000 May;82(5):667-74. doi: 10.2106/00004623-200005000-00007.

    PubMed 10819277

  • Jaffe N, Paed D, Farber S, Traggis D, Geiser C, Kim BS, Das L, Frauenberger G, Djerassi I, Cassady JR. Favorable response of metastatic osteogenic sarcoma to pulse high-dose methotrexate with citrovorum rescue and radiation therapy. Cancer. 1973 Jun;31(6):1367-73. doi: 10.1002/1097-0142(197306)31:63.0.co;2-6. No abstract available.

    PubMed 4541163

  • Gasparini M, Rouesse J, van Oosterom A, Wagener T, Somers R, Russel JA, Voute PA, Bramwell V, Thomas D, Sylvester R, et al. Phase II study of cisplatin in advanced osteogenic sarcoma. European Organization for Research on Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Cancer Treat Rep. 1985 Feb;69(2):211-3.

    PubMed 3855699

  • Marti C, Kroner T, Remagen W, Berchtold W, Cserhati M, Varini M. High-dose ifosfamide in advanced osteosarcoma. Cancer Treat Rep. 1985 Jan;69(1):115-7.

    PubMed 3855382

  • Cores EP, Holland JF, Wang JJ, Sinks LF. Doxorubicin in disseminated osteosarcoma. JAMA. 1972 Sep 4;221(10):1132-8. doi: 10.1001/jama.221.10.1132. No abstract available.

    PubMed 4512088

  • Rosen G, Caparros B, Huvos AG, Kosloff C, Nirenberg A, Cacavio A, Marcove RC, Lane JM, Mehta B, Urban C. Preoperative chemotherapy for osteogenic sarcoma: selection of postoperative adjuvant chemotherapy based on the response of the primary tumor to preoperative chemotherapy. Cancer. 1982 Mar 15;49(6):1221-30. doi: 10.1002/1097-0142(19820315)49:63.0.co;2-e.

    PubMed 6174200

  • Bielack SS, Kempf-Bielack B, Delling G, Exner GU, Flege S, Helmke K, Kotz R, Salzer-Kuntschik M, Werner M, Winkelmann W, Zoubek A, Jurgens H, Winkler K. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol. 2002 Feb 1;20(3):776-90. doi: 10.1200/JCO.2002.20.3.776.

    PubMed 11821461

  • Souhami RL, Craft AW, Van der Eijken JW, Nooij M, Spooner D, Bramwell VH, Wierzbicki R, Malcolm AJ, Kirkpatrick A, Uscinska BM, Van Glabbeke M, Machin D. Randomised trial of two regimens of chemotherapy in operable osteosarcoma: a study of the European Osteosarcoma Intergroup. Lancet. 1997 Sep 27;350(9082):911-7. doi: 10.1016/S0140-6736(97)02307-6.

    PubMed 9314869

  • Claude L, Rousmans S, Carrie C, Breteau N, Dijoud F, Gentet JC, Giammarile F, Jouve JL, Kind M, Marec-Berard P, Mascard E, Bataillard A, Philip T; Institut National du Cancer; Fedeation nationale des centres de lutte contre le cancer (FNCLCC); Standards, Options et Recommendations; Ligue nationale contre le cancer; SFCE; Fedeation hospitaliere de France; FNCHRU; Fedeation francaise de cancerologie. [Standards and Options for the use of radiation therapy in the management of patients with osteosarcoma. Update 2004]. Bull Cancer. 2005 Oct;92(10):891-906. French.

    PubMed 16266873

  • Franzius C, Schuck A, Bielack SS. High-dose samarium-153 ethylene diamine tetramethylene phosphonate: low toxicity of skeletal irradiation in patients with osteosarcoma and bone metastases. J Clin Oncol. 2002 Apr 1;20(7):1953-4. doi: 10.1200/JCO.2002.20.7.1953. No abstract available.

    PubMed 11919261

  • Harris MB, Gieser P, Goorin AM, Ayala A, Shochat SJ, Ferguson WS, Holbrook T, Link MP. Treatment of metastatic osteosarcoma at diagnosis: a Pediatric Oncology Group Study. J Clin Oncol. 1998 Nov;16(11):3641-8. doi: 10.1200/JCO.1998.16.11.3641.

    PubMed 9817286

  • Mialou V, Philip T, Kalifa C, Perol D, Gentet JC, Marec-Berard P, Pacquement H, Chastagner P, Defaschelles AS, Hartmann O. Metastatic osteosarcoma at diagnosis: prognostic factors and long-term outcome--the French pediatric experience. Cancer. 2005 Sep 1;104(5):1100-9. doi: 10.1002/cncr.21263.

    PubMed 16015627

  • Crompton BD, Goldsby RE, Weinberg VK, Feren R, O'Donnell RJ, Ablin AR. Survival after recurrence of osteosarcoma: a 20-year experience at a single institution. Pediatr Blood Cancer. 2006 Sep;47(3):255-9. doi: 10.1002/pbc.20580.

    PubMed 16123980

  • Ferrari S, Briccoli A, Mercuri M, Bertoni F, Cesari M, Longhi A, Bacci G. Late relapse in osteosarcoma. J Pediatr Hematol Oncol. 2006 Jul;28(7):418-22. doi: 10.1097/01.mph.0000212944.82361.1d.

    PubMed 16825986

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Thiotepa in people with Osteosarcoma, run by Centre Leon Berard at 23 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Estimate the overall survival rate (time frame: 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00978471, which also lists 46 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 May 2019.

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