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Phase II Study of Regorafenib in Metastatic Soft Tissue Sarcoma (REGO-SARC)

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ClinicalTrials.gov Identifier: NCT01900743
Recruitment Status : Active, not recruiting
First Posted : July 16, 2013
Last Update Posted : April 3, 2018
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Centre Oscar Lambret

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.


Condition or disease Intervention/treatment Phase
Sarcoma Drug: Regorafenib Drug: Placebo Phase 2

Detailed Description:

The standard of care for metastatic soft tissue sarcoma is doxorubicin +/- ifosfamide. After failure or intolerance to doxorubicin, there is no standard of care. In Europe, two are currently approved for the treatment of soft tissue sarcoma after failure/intolerance to doxorubicin: trabectedin (Yondelis®) for all histological subtype and pazopanib (Votrient ®) for all subtypes excluding liposarcomas. Nevertheless, none of these drugs improve the overall survival over placebo.

The study is composed of 3 periods:

  1. A Screening Period,
  2. A Treatment Period,
  3. And a Survival Follow-up Period. Patients randomized to be treated with regorafenib will receive the treatment orally for 3 weeks of every 4 week (28 days) cycle (ie, 3 weeks on/1 week off).

Patients randomized to the placebo arm will be treated for 3 weeks of every 4 weeks cycle (ie, 3 weeks on/1 week off).

In addition to the regorafenib and placebo treatments, patients will receive best supportive care. Best supportive care includes any method to preserve the comfort and dignity of the patients and excludes any disease-specific anti-neoplastic therapy such as any kinase inhibitor,chemotherapy, radiation therapy, or surgical intervention.

Patients receiving placebo, who experience disease progression may be offered open-label regorafenib(cross-over option).


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 219 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Activity and Safety of Regorafenib in Patients With Metastatic Soft Tissue Sarcoma Previously Treated With Anthracycline-based Chemotherapy : a Multinational, Randomized, Phase II, Placebo-controlled Trial
Actual Study Start Date : June 5, 2013
Estimated Primary Completion Date : February 2019
Estimated Study Completion Date : March 31, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Regorafenib

Arm Intervention/treatment
Experimental: Arm A
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
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.
Other Name: stivarga

Placebo Comparator: Arm B
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
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




Primary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: Up to 2 years ]

    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



Secondary Outcome Measures :
  1. Growth modulation index [ Time Frame: Up to 2 years ]
    Growth modulation index in patients receiving regorafenib after randomization

  2. Toxicity according to NCI-CTC AE V4.0. [ Time Frame: Baseline, every 4 weeks, up to the end of study ]
    The monitoring of the toxicity of the regorafenib which can have a liver toxicity for exemple.

  3. Progression-free rate at 3 and 6 months (PFR-3 and PFR-6) [ Time Frame: At month 3 and at month 6 ]
    According to the RECIST 1.1

  4. Time to progression [ Time Frame: Up to 2 years ]
    According to the RECIST 1.1 Every 4 weeks, Up to 2 years

  5. Overall survival [ Time Frame: Up to 2 years ]
    Time from the date of randomization to the date of death from any cause

  6. Response rate [ Time Frame: Up to 2 years ]
    the proportion of patients with the best overall tumor response of partial response (PR) or complete response (CR) according to RECIST 1.1 guidelines that is achieved during treatment or within 30 days after termination of study medication.

  7. Duration of response [ Time Frame: Up to 2 years ]
    the number of days from the date of first documented objective response of PR or CR, whichever is noted earlier, to first disease progression or death before progression. Patients without progression or death before progression at the time of analysis will be censored at the date of their last tumor assessment.


Other Outcome Measures:
  1. Potential predictive factors for regorafenib response. [ Time Frame: Up to 2 years ]
    The monitoring of the factors which can induce a regorafenib response (Formalin fixed, paraffin embedded (FFPE) or fresh frozen tissue samples collected either from the primary tumor or from metastatic sites, or both will be analyzed)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • Evidence or history of bleeding diathesis. Any hemorrhage or bleeding event > Grade 3 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, including lactose
  • Interstitial lung disease with ongoing signs and symptoms at the time of informed consent
  • Inability to swallow, malabsorption condition
  • Pleural effusion or ascites that causes respiratory compromise (Grade 2 dyspnea)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01900743


Locations
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Austria
Medizinische Universität Graz
Graz, Austria, 8036
Universitätsklinik für Innere Medizin I
Innsbruck, Austria, 6020
LKH
Klagenfurt, Austria
Krankenhaus der Barmherzigen Schwestern Linz
Linz, Austria, 4010
AKH-Wien
Wien, Austria, 1090
France
Hôpital St Jacques
Besancon, France, 25000
Institut Bergonié
Bordeaux, France, 33076
Centre François Baclesse
Caen, France, 14076
Centre GF Leclercq
Dijon, France, 21079
Centre Oscar Lambret
Lille, France, 59020
Centre Léon Bérard
Lyon, France, 69373
Institut Paoli Calmettes
Marseille, France, 13273
Hôpital de La Timone
Marseille, France, 13354
Centre René Gauducheau
Nantes, France, 44805
Centre Antoine Lacassagne
Nice, France, 06189
Institut Curie
Paris, France, 75005
Hôpital Saint Louis
Paris, France, 75010
Hôpital Cochin
Paris, France, 75014
Centre Eugène Marquis
Rennes, France, 35042
Centre Henri Becquerel
Rouen, France, 76038
Institut Curie - Hôpital René Huguenin
Saint Cloud, France, 92210
Institut de Cancérologie Lucien Neuwirth (ICL)
St Priest En Jarez, France, 42270
Institut Claudius Regaud
Toulouse, France, 32052
Centre Alexis Vautrin
Vandoeuvre Les Nancy, France, 54519
Institut Gustave Roussy
Villejuif, France, 94800
Sponsors and Collaborators
Centre Oscar Lambret
Bayer
Investigators
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Study Director: PENEL Nicolas, MD, PhD Centre Oscar Lambret - France
Principal Investigator: Thomas BRODOWICZ, MD, PhD AKH-Wien - Austria

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Centre Oscar Lambret
ClinicalTrials.gov Identifier: NCT01900743     History of Changes
Other Study ID Numbers: REGO-SARC-1214
2012-005743-24 ( EudraCT Number )
First Posted: July 16, 2013    Key Record Dates
Last Update Posted: April 3, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Centre Oscar Lambret:
Sarcoma
Metastatic
Regorafenib
Additional relevant MeSH terms:
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Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms