Phase II Study of Regorafenib in Metastatic Soft Tissue Sarcoma

NCT01900743 | Completed Phase 2 DMC

• 2 other identifiers: REGO-SARC-12142012-005743-24
• Study Type: interventional
• Target: 219
• Locations: 2 countries
• Sites: 25

Brief Summary

This is an international (France, Austria and Germany), randomized, double-blind, placebo-controlled, phase II study to evaluate the efficacy and safety of regorafenib in patients with histologically proven metastatic and/or unresectable Soft Tissue Sarcoma (STS) after failure or intolerance to doxorubicin (or other anthracycline). Five cohorts will be defined: Cohort A: Liposarcoma Cohort B: Leiomyosarcoma Cohort C: Synovial sarcoma Cohort D: other sarcomas (see Appendix C) Cohort E: Leiomyosarcoma, Synovial sarcoma and other sarcomas listed in Appendix C previously treated with pazopanib Approximately 226 patients who meet the eligibility criteria will be randomly assigned in a 1:1 ratio to one of the treatment groups.

Conditions

Sarcoma

Keywords

Sarcoma; Metastatic; Regorafenib

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  Progression-Free Survival will be measured from the date of randomization until the date of radiological progression or death (if death occurs before progression). Progression-free rate at 3 and 6 months (PFR-3 and PFR-6), time to progression, response rate and duration of response, overall survival according to RECIST 1.1 criteria

  Up to 2 years

Secondary Outcomes (7)

• Growth modulation index

  Up to 2 years

• Toxicity according to NCI-CTC AE V4.0.

  Baseline, every 4 weeks, up to the end of study

• Progression-free rate at 3 and 6 months (PFR-3 and PFR-6)

  At month 3 and at month 6

• Time to progression

  Up to 2 years

• Overall survival

  Up to 2 years

Other Outcomes (1)

• Potential predictive factors for regorafenib response.

  Up to 2 years

Study Arms (2)

Arm A

EXPERIMENTAL

Regorafenib (160 mg/d) once daily for 3 weeks on / 1 week off plus Best Supportive Care (BSC) until progression (according to RECIST 1.1), intolerance or consent withdrawal.

Drug: Regorafenib

Arm B

PLACEBO COMPARATOR

Placebo plus BSC until progression (according to RECIST 1.1) or unacceptable toxicity. Patients who have received placebo may be offered open-label regorafenib (cross-over option) after objective tumor progression

Drug: Placebo

Interventions

Regorafenib DRUG

Regorafenib (160 mg/d) once daily for three weeks on / one week off plus Best Supportive Care (BSC)until progression (according to RECIST 1.1), intolerance or consent withdrawal.

Also known as: stivarga

Arm A

Placebo DRUG

Placebo plus BSC until progression (according to RECIST 1.1) or unacceptable toxicity. Patients who have received placebo may be offered open-label regorafenib (cross-over option) after objective tumor progression

Arm B

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years
• Histological documentation of soft tissue sarcoma (including uterus)with available Formalin Fixed Paraffin Embedded (FFPE) blocks. Eligible soft tissue sarcomas are non-adipocytic soft tissue sarcomas
• Prior treatment with doxorubicin or other anthracycline. Moreover, patients eligible in the Cohort E must have received pazopanib
• Metastatic disease not amenable to surgical resection with curative intent
• Documentation of progression within the last 6 months
• Measurable disease, defined as at least 1 unidimensionally measurable lesion on a CT scan as defined by RECIST 1.1.
• Performance status ≤1(ECOG)
• Life expectancy ≤ 3 months
• Adequate bone marrow, renal, and hepatic function:
• INR/PTT ≤1.5 x ULN Patients who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists. Close monitoring will be performed until INR/PTT is stable.
• Women of childbearing potential and male patients must agree to use adequate contraception for the duration of study participation and up to 3 months following completion of therapy.
• Recovery to NCI-CTCAE v4.0 Grade 0 or 1 level or recovery to baseline preceding the prior treatment from any previous drug/procedure related toxicity (except alopecia, anemia, and hypothyroidism).
• In the assessment of the investigator, patient is able to comply with study requirements
• Signed, IRB-approved written informed consent

You may not qualify if:

• More than 3 lines of systemic treatment for metastatic sarcoma
• Histological subtypes listed in Appendix C (especially GIST, osseous sarcoma, embryonal or alveolar rhabdomyosarcoma). Patients with liposarcoma are not eligible in the cohort E
• Primary bone sarcoma
• Prior treatment with regorafenib
• Known history of or concomitant malignancy likely to affect life expectancy in the judgment of the investigator
• Pregnant or breastfeeding patients. Women of childbearing potential must have a pregnancy test performed before start of treatment
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of treatment
• Active cardiac disease including any of the following: Congestive heart failure (NYHA) ≥Class 2, Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months), Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
• Uncontrolled hypertension (SBP \>150 mmHg or diastolic pressure \>90 mmHg despite optimal medical management)
• 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)
• Ongoing infection \>Grade 2 according to NCI-CTCAE v4.0
• Known history of human immunodeficiency virus (HIV) infection
• Known history of chronic hepatitis B or C
• Patients with seizure disorder requiring medication
• History of organ allograft

Sponsors & Collaborators

• Centre Oscar Lambret: lead
• Bayer: collaborator

Study Sites (25)

Medizinische Universität Graz

Graz, 8036, Austria

Location

Universitätsklinik für Innere Medizin I

Innsbruck, 6020, Austria

Location

LKH

Klagenfurt, Austria

Location

Krankenhaus der Barmherzigen Schwestern Linz

Linz, 4010, Austria

Location

AKH-Wien

Vienna, 1090, Austria

Location

Hôpital St Jacques

Besançon, 25000, France

Location

Institut Bergonié

Bordeaux, 33076, France

Location

Centre François Baclesse

Caen, 14076, France

Location

Centre GF Leclercq

Dijon, 21079, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

Institut Paoli Calmettes

Marseille, 13273, France

Location

Hôpital de La Timone

Marseille, 13354, France

Location

Centre René Gauducheau

Nantes, 44805, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Institut Curie

Paris, 75005, France

Location

Hôpital Saint Louis

Paris, 75010, France

Location

Hôpital Cochin

Paris, 75014, France

Location

Centre Eugène Marquis

Rennes, 35042, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

Institut Curie - Hôpital René Huguenin

Saint-Cloud, 92210, France

Location

Institut de Cancérologie Lucien Neuwirth (ICL)

Saint-Priest-en-Jarez, 42270, France

Location

Institut Claudius Regaud

Toulouse, 32052, France

Location

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, 54519, France

Location

Institut Gustave Roussy

Villejuif, 94800, France

Location

Related Publications (5)

• Penel N, Mir O, Wallet J, Ray-Coquard I, Le Cesne A, Italiano A, Salas S, Delcambre C, Bompas E, Bertucci F, Saada-Bouzid E, Chaigneau L, Chevreau C, Brodowicz T, Decoupigny E, Vanseymortier M, Laroche L, Taieb S, Le Deley MC, Blay JY. A double-blind placebo-controlled randomized phase II trial assessing the activity and safety of regorafenib in non-adipocytic sarcoma patients previously treated with both chemotherapy and pazopanib. Eur J Cancer. 2020 Feb;126:45-55. doi: 10.1016/j.ejca.2019.12.001. Epub 2020 Jan 6.

  PMID: 31918233 DERIVED

• Longue M, Cabarrou B, Wallet J, Brodowicz T, Roche H, Boher JM, Delord JP, Penel N, Filleron T. The importance of jointly analyzing treatment administration and toxicity associated with targeted therapies: a case study of regorafenib in soft tissue sarcoma patients. Ann Oncol. 2018 Jul 1;29(7):1588-1593. doi: 10.1093/annonc/mdy168.

  PMID: 29722789 DERIVED

• Berry V, Basson L, Bogart E, Mir O, Blay JY, Italiano A, Bertucci F, Chevreau C, Clisant-Delaine S, Liegl-Antzager B, Tresch-Bruneel E, Wallet J, Taieb S, Decoupigny E, Le Cesne A, Brodowicz T, Penel N. REGOSARC: Regorafenib versus placebo in doxorubicin-refractory soft-tissue sarcoma-A quality-adjusted time without symptoms of progression or toxicity analysis. Cancer. 2017 Jun 15;123(12):2294-2302. doi: 10.1002/cncr.30661. Epub 2017 Mar 10.

  PMID: 28295221 DERIVED

• Mir O, Brodowicz T, Italiano A, Wallet J, Blay JY, Bertucci F, Chevreau C, Piperno-Neumann S, Bompas E, Salas S, Perrin C, Delcambre C, Liegl-Atzwanger B, Toulmonde M, Dumont S, Ray-Coquard I, Clisant S, Taieb S, Guillemet C, Rios M, Collard O, Bozec L, Cupissol D, Saada-Bouzid E, Lemaignan C, Eisterer W, Isambert N, Chaigneau L, Cesne AL, Penel N. Safety and efficacy of regorafenib in patients with advanced soft tissue sarcoma (REGOSARC): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1732-1742. doi: 10.1016/S1470-2045(16)30507-1. Epub 2016 Oct 14.

  PMID: 27751846 DERIVED

• Brodowicz T, Liegl-Atzwager B, Tresch E, Taieb S, Kramar A, Gruenwald V, Vanseymortier M, Clisant S, Blay JY, Le Cesne A, Penel N. Study protocol of REGOSARC trial: activity and safety of regorafenib in advanced soft tissue sarcoma: a multinational, randomized, placebo-controlled, phase II trial. BMC Cancer. 2015 Mar 14;15:127. doi: 10.1186/s12885-015-1143-y.

  PMID: 25884155 DERIVED

MeSH Terms

Conditions

Sarcoma; Neoplasm Metastasis

Interventions

regorafenib

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Nicolas PENEL, PhD

  Centre Oscar Lambret - France

  STUDY DIRECTOR

• Thomas BRODOWICZ, PhD

  AKH-Wien - Austria

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 9, 2013
• First Posted: July 16, 2013
• Study Start: June 5, 2013
• Primary Completion: September 16, 2020
• Study Completion: September 16, 2020
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (20); AU (5)