Efficacy of Regorafenib Combined With Best Supportive Care as Maintenance Treatment in High Grade Bone Sarcomas Patients
- Conditions
- OsteosarcomaBone Sarcoma
- Interventions
- Drug: Treatment by regorafenib and best supportive care
- Registration Number
- NCT04698785
- Lead Sponsor
- Centre Leon Berard
- Brief Summary
This is a randomized, double-blinded, 2 arms study concerning patients with high-grade bone sarcoma (HGBS) without complete remission after standard treatment at diagnosis or first relapse.
In the first arm, patients will be treated with regorafenib + best supportive care (BSC) for a maximum of 12 months as maintenance therapy after standard line therapy completion, whereas in the second arm, patients will be treated with placebo + BSC (standard of care).
The comparison between this two arms will allow to determine whether or not regorafenib and BSC is efficient for disease control, in terms of Progression-Free Survival improvement.
- Detailed Description
This is a randomized, placebo-controlled, double-blinded, prospective, comparative, multicentre phase II study.
Patients with measurable unresectable residual disease will be accrued after they completed standard of care, consisting of:
* At diagnosis: multimodal treatment with neoadjuvant chemotherapy, surgery and adjuvant chemotherapy
* At relapse: chemotherapy
Patients who meet the eligibility criteria will be randomly assigned (1:1) into one of the following treatment groups:
* Experimental arm: regorafenib + best supportive care (BSC) maintenance (12 months maximum)
* Standard arm: placebo + BSC (12 months maximum)
A randomization procedure (centralized implementation of concealed random permuted blocks) will be used to obtain a balanced distribution of the setting of the disease (stratification factor): residual disease at diagnosis or at relapse after standard multimodal treatment.
After their eligibility has been confirmed, patients will receive regorafenib or its matching placebo until disease progression, or for a maximum of 12 months, or unacceptable toxicity or willingness to stop, whichever occurs first.
In case of radiological disease progression during treatment period, patients from the standard arm (placebo) who have unresectable disease will be allow to switch to experimental arm (regorafenib). After the switch, patients will be treated with regorafenib until disease progression or unacceptable toxicity or willingness to stop which occurs first.
After the completion of the maintenance therapy (12 months) patients will be followed-up until the first radiological disease progression, unless a premature disease progression occurred. All patients will be followed-up until the data cut-off (12 months after the last randomization).
The vital status will be updated once for all patients at the end of the study, based on patient's medical file.
The end of the study will be 24 months after the last randomisation or at the end of treatment of the last patient under treatment (either blinded or open label) whichever occurs last.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 60
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Regorafenib and best supportive care Treatment by regorafenib and best supportive care Treatment will be divided in 28 days cycles, including a 21-day period of treatment by regorafenib and best supportive care 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).
- Primary Outcome Measures
Name Time Method Progression-Free Rate at 4 months (4m-PFR) Up to 16 weeks after the date of regorafenib + BSC treatment initiation The Progression-Free Rate at 4 months (4m-PFR) will be defined as the proportion of patients with a complete response, a partial response or stable disease, confirmed on tumour assessments according to the RECIST V1.1 at 4 months (16 weeks) after the date of regorafenib + BSC treatment initiation.
Patients with a non-progressive disease at 16 ± 2 weeks after the date of regorafenib + BSC treatment initiation will be considered as "success" patients.
Patients with a progressive disease and patients who died from any cause at 16 ± 2 weeks after the date of regorafenib + BSC treatment initiation will be considered as "failure" patients.
At the time of analysis, if at least 18 "successes" are observed among the 36 analyzed patients, the regorafenib + BSC treatment will be considered as interesting for further investigations in this indication.
- Secondary Outcome Measures
Name Time Method Progression-Free Survival (PFS) Up to 3 years PFS will be described from date of regorafenib + BSC treatment initiation to the date first documented disease progression according to RECIST V1.1 or the date of death due to any cause.
Patients alive without progression at the time of data cut-off will be censored at the time of latest tumour evaluation.Objective Response Rate (ORR) Up to 3 years The Objective Response Rate (ORR) will be defined as the proportion of patients with a best overall response of Complete Response (CR) or Partial Response (PR) (RECIST V1.1)
Disease Control Rate (DCR) at 2 months 2 months The Disease Control Rate (DCR) will be defined as the proportion of patients with a best overall response of CR, PR or Stable Disease (SD) (RECIST V1.1) 2 months after randomization
Disease Control Rate (DCR) at 4 months 4 months The Disease Control Rate (DCR) will be defined as the proportion of patients with a best overall response of CR, PR or Stable Disease (SD) (RECIST V1.1) 4 months after randomization
Overall Survival (OS) Up to 3 years The Overall Survival (OS) will be defined as the time from date of regorafenib +BSC treatment initiation to the date of death, from any cause. Patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive.
Quality of Life (QoL) Up to 1 year The patient's Quality of Life (QoL) will be assessed using the EORTC Quality Of Life Questionnaire (QLQ)-C30 file. Scores will be calculated at each time point according to the scoring manuals. Descriptive statistics will be used to evaluate baseline scores and evolution of scores from baseline to each time point. Data will be compared between arms using the Student's t-test. The QoL data will also be presented graphically if deemed relevant.
Tolerance profile of treatment Up to 3 years The safety will be described mainly on the frequency of adverse events (AE) coded using the common toxicity criteria (NCI-CTCAE v5.0) grade. Descriptive statistics will be provided for characterizing and assessing patient tolerance to treatment. AE will be coded according to the MedDRA®.
Trial Locations
- Locations (16)
Chu Besancon
🇫🇷Besançon, France
Institut Bergonie
🇫🇷Bordeaux, France
Centre Georges Francois Leclerc
🇫🇷Dijon, France
Centre Oscar Lambret
🇫🇷Lille, France
Centre Leon Berard
🇫🇷Lyon, France
Hopital de La Timone
🇫🇷Marseille, France
Icm Val D'Aurelle
🇫🇷Montpellier, France
Hotel Dieu Nantes
🇫🇷Nantes, France
Institut Curie
🇫🇷Paris, France
Hôpital COCHIN
🇫🇷Paris, France
Ico Rene Gauducheau
🇫🇷Saint-Herblain, France
Chu Saint-Etienne
🇫🇷Saint-Priest-en-Jarez, France
CHRU Hôpital Hautepierre
🇫🇷Strasbourg, France
ICANS
🇫🇷Strasbourg, France
Iuct Oncopole
🇫🇷Toulouse, France
Institut Gustave Roussy
🇫🇷Villejuif, France