Phase II Study of Regorafenib as Maintenance Therapy

NCT03793361 | Completed Phase 2 DMC

• 3 other identifiers: EREMISS-1801PHRC-K18-1582018-001574-22
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 20

Brief Summary

Multicenter double-blind placebo-controlled randomized Phase II study comparing regorafenib® to placebo, as maintenance therapy in metastatic soft-tissue non-adipocytic sarcomas experiencing stable disease or response after 6 cycles of doxorubicin-based chemotherapy as 1st line chemotherapy.

Conditions

Metastatic Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (1)

• To assess the efficacy of regorafenib compared to placebo

  Progression-Free Survival will be measured from the date of randomization until the date of radiological progression (according to RECIST 1.1 criteria) or death (if death occurs before progression).

  from the date of randomization to the date of first observed disease progression (according to RECIST 1.1 criteria) or death from any cause, up to 12 months after the beginning of the treatment

Secondary Outcomes (5)

• To assess the efficacy of regorafenib compared to placebo

  from the date of randomization to the date of death from any cause

• To assess the efficacy of regorafenib compared to placebo

  from the date of randomization to the date of first observed disease progression (according to RECIST 1.1) or death from any cause, up to 12 months after the beginning of the treatment

• To assess the efficacy of regorafenib compared to placebo

  from the date of randomization to the date of death from any cause, up to 12 months after the beginning of the treatment

• To assess the safety of regorafenib

  Baseline, every 4 weeks, up to 12 months after the beginning of the treatment

• To assess the relative benefit/risk ratio

  up to 12 months

Other Outcomes (1)

• assessment of the predictive value of SUMSCAN signature

  up to 12 months

Study Arms (2)

Arm A

EXPERIMENTAL

Regorafenib

Drug: Regorafenib

Arm B

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Regorafenib DRUG

Oral Drug in the form of 40 mg tablets - Regorafenib (120 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. Provided by BAYER

Also known as: stivarga

Arm A

Placebo DRUG

Oral tablets - 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 Provided by BAYER

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
• Histologically proven soft tissue sarcoma including leiomyosarcoma, synovial sarcoma and other sarcomas
• Patients in partial response or stable disease after 6 cycles of doxorubicin-based first-line chemotherapy for metastatic/locally advanced soft tissue sarcoma
• Metastatic/locally advanced disease not amenable to surgical resection with curative intent
• Eastern Cooperative Oncology Group (ECOG) Performance Status =0 or 1
• Measurable disease, defined as at least 1 unidimensionally measurable lesion on a CT scan as defined by RECIST 1.1.
• Available tumor tissue for translational research program
• Adequate bone marrow, renal, and hepatic function, as evidenced by the following within 7 days of study treatment initiation:
• Absolute neutrophil count (ANC) ≥1,500/mm3
• Platelets ≥100,000/mm3
• Hemoglobin ≥9.0 g/dL
• Serum creatinine ≤1.5 x upper limit of normal (ULN)
• Glomerular filtration rate (GFR) ≥30 ml/min/1.73m2
• AST and ALT ≤2.5 x ULN ( ≤5.0 × ULN for patients with liver involvement of their cancer)
• Bilirubin ≤1.5 X ULN

You may not qualify if:

• Prior adjuvant or neoadjuvant chemotherapy not allowing at least 6 cycles of doxorubicin-based chemotherapy at metastatic stage
• Complete response to 1st line chemotherapy for metastatic/locally advanced soft tissue sarcoma
• Disease progression during the 1st line of chemotherapy
• Time interval between the last cycle of doxorubicin-based chemotherapy superior to 8 weeks
• Primary bone sarcoma
• All forms of liposarcoma
• Some particular histologic types, i.e., PNET/Ewing, alveolar or embryonal rhabdomyosarcoma, Perivascular epithelioid cell sarcoma (PECoMA), low grade endometrial stromal tumor, desmoid tumor
• Prior treatment with tyrosine kinase inhibitor
• 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 a maximum of 7 days before start of treatment
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of Day 1 of treatment
• Active cardiac disease including any of the following: Congestive heart failure (New York Heart Association \[NYHA\]) ≥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 (Systolic blood pressure \>150 mmHg or diastolic pressure \>90 mmHg despite optimal medical management)
• Arterial or venous thrombotic or embolic events such as myocardial infarction, cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within 6 months of starting on study drug
• Any hemorrhage or bleeding event \> Grade 4 within 4 weeks of start of treatment

Sponsors & Collaborators

• Centre Oscar Lambret: lead

Study Sites (20)

CHRU Besançon

Besançon, 25000, France

Location

Institut Bergonié

Bordeaux, 33076, France

Location

Centre François Baclesse

Caen, 14076, France

Location

Centre Georges-François LECLERC

Dijon, 21079, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

Hôpital La Timone

Marseille, 13005, France

Location

Institut Paoli-Calmettes

Marseille, 13273, France

Location

Institut régional du Cancer de Montpellier

Montpellier, 34298, France

Location

Centre René Gauducheau

Nantes, 44805, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Institut Curie

Paris, 75005, France

Location

Chu Poitiers

Poitiers, 86000, France

Location

Institut Godinot

Reims, 51100, France

Location

Centre Eugène Marquis

Rennes, 35042, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

Institut de Cancérologie Lucien Neuwirth

Saint-Priest-en-Jarez, 42270, France

Location

Hôpitaux universitaires de Strasbourg

Strasbourg, 67000, France

Location

Institut Claudius Regaud

Toulouse, 31059, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

MeSH Terms

Conditions

Sarcoma

Interventions

regorafenib

Condition Hierarchy (Ancestors)

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

Study Officials

• Nicolas PENEL, PhD

  Centre Oscar Lambret

  STUDY DIRECTOR

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: December 28, 2018
• First Posted: January 4, 2019
• Study Start: May 15, 2019
• Primary Completion: March 15, 2024
• Study Completion: September 26, 2024
• Last Updated: March 18, 2026

Record last verified: 2024-06

Locations

FR (20)