Phase II Study of Regorafenib as Maintenance Therapy

NCT ID: NCT03793361

Last Updated: 2024-12-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

127 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-05-15

Study Completion Date

2024-09-26

Brief Summary

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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.

Detailed Description

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Patients will be randomized 1:1 using a centralized randomization software, assuring concealment, with a minimization program controlling for the following factors:

* Histological subgroups: leiomyosarcoma versus synovial sarcoma versus other histological subtype
* Response to doxorubicin-based chemotherapy: partial response versus stable disease
* Centers

The treatment will be administrated as long as it appears beneficial. Evaluations will be made every 8 weeks until 6 months and then every 3 months

Conditions

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Metastatic Soft Tissue Sarcoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Arm A

Regorafenib

Group Type EXPERIMENTAL

Regorafenib

Intervention Type 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

Arm B

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type 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

Interventions

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Regorafenib

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

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Other Intervention Names

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stivarga

Eligibility Criteria

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Inclusion Criteria

* 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
* Alkaline phosphatase ≤2.5 x ULN (≤5 x ULN with liver involvement of their cancer)
* Lipase ≤1.5 x ULN
* Spot urine must not show 1+ or more protein in urine or the patient will require a repeat urine analysis. If repeat urinanalysis shows 1+ protein or more, a 24-hour urine collection will be required and must show total protein excretion \<1000 mg/24 hours
* 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 of at least weekly evaluations will be performed until INR/PTT is stable based on a measurement that is pre-dose as defined by the local standard of care.)
* Women of childbearing potential and male subjects must agree to use adequate contraception for the duration of study participation and up to 3 months following completion of therapy. Adequate contraception is defined as any medically recommended method (or combination of methods) as per standard of care.
* Recovery to National Cancer Institute-Common Terminology Criteria for Adverse Events (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, patients are able to comply with study requirements
* Signed, IRB-approved written informed consent
* Patient covered by the French "Social Security" regime

Exclusion Criteria

* 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
* Ongoing infection \>Grade 2 according to NCI Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v. 5.0)
* 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
* Evidence or history of bleeding diathesis. Any hemorrhage or bleeding event \> Grade 4 within 4 weeks of start of treatment
* Non-healing wound, ulcer, or bone fracture
* Renal failure requiring hemo- or peritoneal dialysis
* Dehydration according to NCI-CTC v 4.0 Grade \>1
* Substance abuse, medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
* Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation
* Interstitial lung disease with ongoing signs and symptoms at the time of informed consent
* Inability to swallow oral medications, Any mal-absorption condition
* Pleural effusion or ascites that causes respiratory compromise (Grade 2 dyspnea)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Centre Oscar Lambret

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Nicolas PENEL, PhD

Role: STUDY_DIRECTOR

Centre Oscar Lambret

Locations

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CHRU Besançon

Besançon, , France

Site Status

Institut Bergonié

Bordeaux, , France

Site Status

Centre François Baclesse

Caen, , France

Site Status

Centre Georges-François LECLERC

Dijon, , France

Site Status

Centre Oscar Lambret

Lille, , France

Site Status

Centre Léon Bérard

Lyon, , France

Site Status

Hôpital La Timone

Marseille, , France

Site Status

Institut Paoli-Calmettes

Marseille, , France

Site Status

Institut régional du Cancer de Montpellier

Montpellier, , France

Site Status

Centre René Gauducheau

Nantes, , France

Site Status

Centre Antoine Lacassagne

Nice, , France

Site Status

Institut Curie

Paris, , France

Site Status

Chu Poitiers

Poitiers, , France

Site Status

Institut Godinot

Reims, , France

Site Status

Centre Eugène Marquis

Rennes, , France

Site Status

Centre Henri Becquerel

Rouen, , France

Site Status

Institut de Cancérologie Lucien Neuwirth

Saint-Priest-en-Jarez, , France

Site Status

Hôpitaux universitaires de Strasbourg

Strasbourg, , France

Site Status

Institut Claudius Regaud

Toulouse, , France

Site Status

Institut Gustave Roussy

Villejuif, , France

Site Status

Countries

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France

Other Identifiers

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EREMISS

Identifier Type: -

Identifier Source: org_study_id