Efficacy and Safety of Regorafenib as Maintenance Therapy After First-line Treatment in Patients With Bone Sarcomas

NCT04055220 | Recruiting DMC

• 1 other identifier: REGOSTA (ET18-272)
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 16

Brief Summary

Randomized, non-comparative, multicentre exploratory phase II study. Two arms concerning patients with bone sarcoma after the first line therapy: in the first arm, patients will be treated with Regorafenib for a maximum of 12 months as maintenance therapy after first line therapy, whereas in the second arm, patients will be kept under surveillance (standard of care). Regardless of their study arm, all the patients will be followed up until end of the study. The comparison between these two arms will allow to determine whether or not regorafenib is efficient for disease control, in terms of Relapse-Free Survival improvement.

Conditions

Bone Sarcoma; Osteosarcoma; Ewing Sarcoma; Chondrosarcoma; Undifferentiated Pleomorphic Sarcoma; Leiomyosarcoma; Angiosarcoma

Keywords

Maintenance therapy; First line therapy; Regorafenib; Randomization; Double-blinded; Placebo controlled; Relapse-free survival; Time to treatment failure; Overall survival; Quality of life; Compliance; Bone sarcoma; Osteosarcoma; Efficacy; Complete response; Tyrosine kinase inhibitor; Multi-target inhibitor; Safety

Outcome Measures

Primary Outcomes (1)

• Relapse-Free Survival (RFS)

  RFS will be defined as the time from randomization to relapse, or death from any cause, whichever occurs first. Patients alive without relapse at the time of the analysis will be censored at the date of last tumour assessment. The Kaplan-Meier approach will be used to estimate median RFS for each study arm. The two-sided log-rank test, stratified on randomization stratification factors, will be used to compare RFS between the investigational arm and the control arm. The stratified Cox-regression (with proportional hazards) will be used to estimate the hazard ratio and to calculate the 95% confidence intervals of the hazard ratio.

  Up to 5 years

Secondary Outcomes (5)

• Time to Treatment Failure (TTF)

  Up to 1 year

• Overall Survival (OS)

  Up to 5 years

• Patient's Quality of Life (QoL)

  Up to 5 years

• Safety profile

  Up to 5 years

• Compliance To Treatment

  Up to 1 year

Study Arms (2)

Regorafenib

EXPERIMENTAL

Treatment will be divided in 28 days cycles, including a 21-day period of treatment by regorafenib followed by a 7-day period of rest. In case of toxicity, dose can be reduced or treatment interrupted according to Specific Product Characteristics (SPC). Patients can receive up to a maximum of 13 cycles (maximum treatment period : 12 Months).

Drug: Treatment by Regorafenib

Surveillance

OTHER

No intervention is performed for patients in this arm; however, they receive the identical surveillance as patients of the experimental arm.

Other: Surveillance

Interventions

Surveillance OTHER

Followed up patients in the exact same way as patients in the experimental arm

Also known as: Standard of care

Surveillance

Treatment by Regorafenib DRUG

Treatment for 13 cycles (12 months) maximum. During each cycle, patient will take once a day, during 21 days, followed by 7 days without treatment : * 3 tablets daily, corresponding to a total of 120 mg of Regorafenib (3 weeks out of 4 weeks) in patients ≥ 16 years old and patients \< 16 years old with BSA ≥ 1.70m²; * 2 tablets daily corresponding to a total of 80 mg of Regorafenib (3 weeks out of 4 weeks) in patients \< 16 years old with 1.30m² ≤ BSA \< 1.70m²;

Also known as: Stivarga

Regorafenib

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• I1. Age ≥ 12 years at the day of consenting to the study;
• I2. Patients must have histologically confirmed diagnosis of primary bone sarcoma including but not limited to: Osteosarcomas, Ewing sarcomas, Chondrosarcomas, Undifferentiated Pleomorphic Sarcomas (UPS), Leiomyosarcomas (LMS) and Angiosarcomas;
• I3. Prior treatment for localized or metastatic disease for bone sarcoma must have been completed, consisting of a standard multimodal treatment based on the histological subtype:
• For OS, (excepted head and neck localisations), neoadjuvant and/or adjuvant chemotherapy should include methotrexate-based regimen for patients \< 18 years old; patients ≥ 18 years old may have received either methotrexate-based regimen or anthracycline and cisplatin-based regimen For head and neck OS, neoadjuvant and/or adjuvant chemotherapy should include adriamycin, cisplatin or ifosfamide-based regimen.
• For non-OS, neoadjuvant and/or adjuvant chemotherapy should include adriamycin and/or cisplatin-based regimen.
• I4. Recovery to NCI-CTCAE v5 Grade 0 or 1 level or recovery to baseline preceding the prior treatment from any previous drug/procedure related toxicity (except alopecia, anaemia, and hypothyroidism);
• I5. Interval between the last chemotherapy administration and the date of randomisation: at least 4 weeks but no longer than 2 months;
• I6. Confirmed complete remission or no evidence of disease (for metastatic disease);
• Patients with pulmonary micro nodules can be included provided they do not meet the following criteria:
• At least one lung nodule of 10mm or more
• And/or at least two nodules well limited between 6-9mm
• And/or at least 5 nodules well limited of 5mm or less All the other situations will be considered as doubtful lesions except in case of metastatic disease confirmed during the lung surgery of the residual lung lesions after pre-operative chemotherapy. If no other metastatic localisation is detected at the initial staging, the patient will be considered as localised disease and eligible for randomisation.
• I7. Life expectancy of greater than 12 months;
• I8. Karnofsky Performance status ≥70 (patients younger than 18-year old) or ECOG performance status \< 2 (adult patients) ;
• I9. Patients must have adequate bone marrow, renal, and hepatic function, as evidenced by the following within 7 days of study treatment initiation:

Sponsors & Collaborators

• Centre Leon Berard: lead

Study Sites (16)

Hôpital Jean Minjoz

Besançon, 25000, France

RECRUITING

Institut Bergonié

Bordeaux, 33076, France

RECRUITING

Centre Oscar Lambret

Lille, 59020, France

RECRUITING

Centre Léon Bérard

Lyon, 69373, France

RECRUITING

APHM - Hôpital Timone

Marseille, 13385, France

RECRUITING

ICM Val d'Aurelle

Montpellier, 34298, France

NOT YET RECRUITING

Institut Curie

Paris, 75005, France

RECRUITING

APHP Hôpital Cochin

Paris, 75014, France

RECRUITING

Centre Hospitalier Universitaire de Poitiers

Poitiers, 86000, France

NOT YET RECRUITING

Centre Hospitalier Universitaire de Saint-Etienne (CHUSE)

Saint-Etienne, 42055, France

RECRUITING

ICO René Gauducheau

Saint-Herblain, 44805, France

RECRUITING

Centre Paul Strauss - Strasbourg

Strasbourg, 67033, France

RECRUITING

Centre Hospitalier Régional de Strasbourg Hautepierre

Strasbourg, 67098, France

RECRUITING

IUCT-Oncopole

Toulouse, 31059, France

NOT YET RECRUITING

ICL Alexis Vautrin

Vandœuvre-lès-Nancy, 54519, France

NOT YET RECRUITING

Institut Gustave Roussy

Villejuif, 94805, France

RECRUITING

MeSH Terms

Conditions

Bone Neoplasms; Osteosarcoma; Sarcoma, Ewing; Chondrosarcoma; Histiocytoma, Malignant Fibrous; Leiomyosarcoma; Hemangiosarcoma; Patient Compliance; Pathologic Complete Response

Interventions

regorafenib; Standard of Care

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Bone Diseases; Musculoskeletal Diseases; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Sarcoma; Histiocytoma; Neoplasms, Fibrous Tissue; Neoplasms, Muscle Tissue; Neoplasms, Vascular Tissue; Patient Acceptance of Health Care; Treatment Adherence and Compliance; Health Behavior; Behavior; Disease Progression; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Jean-Yves BLAY

  Centre Léon Bérard, Lyon

  PRINCIPAL INVESTIGATOR

• Florence DUFFAUD

  Hôpital de la Timone (MARSEILLE)

  PRINCIPAL INVESTIGATOR

• Sophie PIPERNO-NEUMANN

  Institut Curie Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Julien GAUTIER

CONTACT

+33 426 55 68 29; julien.gautier@lyon.unicancer.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2019
• First Posted: August 13, 2019
• Study Start: March 3, 2020
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: February 17, 2026

Record last verified: 2026-02

Locations

FR (16)