A Phase II Study Evaluating Efficacy and Safety of Regorafenib in Patients With Metastatic Bone Sarcomas

NCT02389244 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: UC-0150/13092013-003910-42
• Study Type: interventional
• Target: 163
• Locations: 1 country
• Sites: 19

Brief Summary

INDICATION: Metastatic bone sarcomas: conventional high grade osteosarcoma, Ewing sarcoma of bone, intermediate or high-grade chondrosarcomas and chordomas and either bone or soft tissue metastatic CIC-rearranged sarcomas

Conditions

Ewing Sarcomas; Chondrosarcomas; Osteosarcomas; Chondroma; CIC-Rearranged Sarcoma

Outcome Measures

Primary Outcomes (1)

• Non-progression rate

  Proportion of patients without disease progression at the defined timepoint after central radiological review (using RECIST 1.1)

  8 weeks for cohorts A, B and E, 12 weeks for cohort C, 6 months for cohort D

Secondary Outcomes (11)

• Progression Free Survival

  expected average duration of 3 months

• Objective response rate

  6 months

• Disease control rate at 6 months

  6 months

• Overall survival

  2 years

• Duration of response

  expected average duration of 6 months

Study Arms (2)

Regorafenib

EXPERIMENTAL

For adult patients (≥18 years old) : 160 mg/d once daily for the 3 weeks on / 1 week off plus Best Supportive Care (BSC) until progression (according to RECIST 1.1), intolerance or withdrawal of consent . For children Age ≥10 years to \<18 years old and BSA ≥1.30 m², regorafenib (82 mg/m²) once daily for the 3 weeks on/1 week off (without exceeding 160 mg/day) plus Best Supportive care (BSC) until progression (according to RECIST 1.1), intolerance or withdrawal of consent.

Drug: Regorafenib

placebo

PLACEBO COMPARATOR

Placebo plus BCS until progression (according to RECIST V1.1) intolerance or withdrawal of consent. Patients who have received placebo will receive open-label regorafenib after objective tumor progression.

Drug: Placebo

Interventions

Regorafenib DRUG

For adults patients and children with BSA ≥1.70 m² : 4 tablets once daily until progression or unacceptable toxicity For children with BSA ≥1.30 and ≤1.69 m² : 3 tablets once daily until progression or unacceptable toxicity

Also known as: Stivarga

Regorafenib

Placebo DRUG

For adults patients and children with BSA ≥1.70 m² : 4 tablets once daily and switch to regorafenib after confirmed progression For children with BSA ≥1.30 and ≤1.69 m² : 3 tablets once daily and switch to regorafenib after confirmed progression

Also known as: Placebo tablet

placebo

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed diagnosis of bone sarcoma (osteosarcoma, Ewing sarcoma of bone, chondrosarcoma or chordoma);
• Patients with confirmed disease progression at study entry;
• Metastatic disease not amenable to surgical resection or radiation with curative intent;
• Patients must have measurable disease;
• Prior treatment :
• at least one, but no more than two prior chemotherapy regimen for metastatic disease for osteosarcoma, chondrosarcoma and Ewing sarcoma; neo-adjuvant /maintenance therapy are not counted towards this requirement. Chordoma not pretreated or with 1 or 2 prior (combination) chemotherapy regimen or with one or two prior molecularly targeted therapy, but no more than 2 prior lines of treatment (whatever the indication) can be included. At least 4 weeks since last chemotherapy (6 weeks in case of nitrosoureas and mitomycin C), immunotherapy or any other pharmacological treatment and/or radiotherapy;
• Age ≥10 years for osteosarcomas, Ewing sarcomas and chondrosarcomas (for chordomas, patients must be ≥18 years);
• Body Surface Area ≥1.30 m²;
• Life expectancy of greater than 3 months;
• Eastern Cooperative Oncology Group (ECOG) performance status \<2 (Karnofsky ≥60%) for adults patients;
• Karnofsky scale ≥ 60% for children aged \>12 years old / Lansky scale ≥60% for children aged ≤12 years old;
• Patients must have adequate bone marrow, renal, and hepatic function, as evidenced by the following within 7 days of study treatment initiation: normal organ function as defined below:
• Absolute neutrophil count ≥1.5 Giga/L
• Platelets ≥100 Giga/L
• Hemoglobin ≥9 g/dL

You may not qualify if:

• Prior treatment with any VEGFR inhibitor;
• Soft tissue sarcoma;
• Other cancer (different histology) within 5 years prior to randomization;
• Major surgical procedure, open biopsy, significant trauma, within the last 28 days before randomization;
• Cardiovascular dysfunction:
• Left ventricular ejection fraction (LVEF) \<50%
• Congestive heart failure (New York Heart Association \[NYHA\]) ≥2
• Myocardial infarction \<6 months before study
• Cardiac arrhythmias requiring therapy
• Uncontrolled hypertension
• Unstable angina or new-onset angina
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within the last 6 months before randomization;
• Severe hepatic impairment (Child-Pugh C);
• Ongoing infection \> Grade 2 according to NCI-CTCAE v4.0;
• Known history of human immunodeficiency virus (HIV) infection;

Sponsors & Collaborators

• UNICANCER: lead

Study Sites (19)

Hopital Jean Monjoz

Besançon, 25030, France

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Centre Francois Baclesse

Caen, 14176, France

Location

Centre Georges Francois Leclerc

Dijon, 21079, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Centre Léon Berard

Lyon, 69373, France

Location

Institut Paoli Calmettes

Marseille, 13273, France

Location

La Timone University Hospital

Marseille, 13385, France

Location

ICM Val d'Aurelle

Montpellier, 34298, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Hôpital Cochin

Paris, 75014, France

Location

Institut Curie

Paris, France

Location

Centre Eugene Marquis

Rennes, 35042, France

Location

Institut de cancerologie de l'ouest site Rene Gauducheau

Saint-Herblain, 44805, France

Location

Institut de Cancérologie Lucien Neuwirth (ICLN)

Saint-Priest-en-Jarez, 42270, France

Location

Institut Claudius Regaud

Toulouse, 31052, France

Location

CHU Bretonneau

Tours, 37000, France

Location

Institut de cancerologie de lorraine alexis Vautrin

Vandœuvre-lès-Nancy, 54519, France

Location

Gustave Roussy

Villejuif, 94800, France

Location

Related Publications (3)

• Duffaud F, Italiano A, Bompas E, Rios M, Penel N, Mir O, Piperno-Neumann S, Chevreau C, Delcambre C, Bertucci F, Boudou-Rouquette P, Cancel M, Perrin C, Saada-Bouzid E, Monard L, Schiffler C, Chaigneau L, Hervieu A, Collard O, Bouvier C, Vidal V, Chabaud S, Blay JY; French Sarcoma Group. Efficacy and safety of regorafenib in patients with metastatic or locally advanced chondrosarcoma: Results of a non-comparative, randomised, double-blind, placebo controlled, multicentre phase II study. Eur J Cancer. 2021 Jun;150:108-118. doi: 10.1016/j.ejca.2021.03.039. Epub 2021 Apr 22.

  PMID: 33895682 DERIVED

• 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

• Duffaud F, Mir O, Boudou-Rouquette P, Piperno-Neumann S, Penel N, Bompas E, Delcambre C, Kalbacher E, Italiano A, Collard O, Chevreau C, Saada E, Isambert N, Delaye J, Schiffler C, Bouvier C, Vidal V, Chabaud S, Blay JY; French Sarcoma Group. Efficacy and safety of regorafenib in adult patients with metastatic osteosarcoma: a non-comparative, randomised, double-blind, placebo-controlled, phase 2 study. Lancet Oncol. 2019 Jan;20(1):120-133. doi: 10.1016/S1470-2045(18)30742-3. Epub 2018 Nov 23.

  PMID: 30477937 DERIVED

MeSH Terms

Conditions

Chondrosarcoma; Osteosarcoma; Chondroma

Interventions

regorafenib

Condition Hierarchy (Ancestors)

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

Study Officials

• Florence DUFFAUD, MD PhD

  La Timone University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2015
• First Posted: March 17, 2015
• Study Start: September 1, 2014
• Primary Completion: October 25, 2024
• Study Completion: March 11, 2026
• Last Updated: September 16, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (19)