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LiposarcomaPhase 2NCT02048371

SARC024: A Blanket Protocol to Study Oral Regorafenib in Patients With Selected Sarcoma Subtypes

A Phase 2 study testing Regorafenib in people with Liposarcoma and Osteogenic Sarcoma, run by Sarcoma Alliance for Research through Collaboration at 18 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Although regorafenib was approved for use in patients who had progressive GIST despite imatinib and/or sunitinib on the basis of phase II and phase III data, it has not been examined in a systematic fashion in patients with other forms of sarcoma. Read more about this study

Who is it for?
Ages 5 years and older
What is being tested?
Regorafenib
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
131 participants
Where
18 sitesUnited States
Study dates
Jul 2014to May 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 5 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Age ≥ 10 year for Liposarcoma, Osteosarcoma, Ewing sarcoma and Mesenchymal Chondrosarcoma; Age ≥ 5 years for Rhabdomyosarcoma cohorts
  • Weight ≥ 15 kg (33 lb)
  • Patients must have histologically or cytologically confirmed advanced/metastatic liposarcoma, osteogenic sarcoma, Ewing/Ewing-like sarcoma of soft tissue or bone, fusion-positive alveolar rhabdomyosarcoma or embryonal rhabdomyosarcoma/fusion-negative alveolar rhabdomyosarcoma , or mesenchymal chondrosarcoma
  • WHO Performance Status 0, 1 or 2. A maximum of 1/3 of patients in cohorts A \& B may be WHO performance status 2
  • At least one prior line of systemic therapy for the sarcoma diagnosis (neoadjuvant, adjuvant or metastatic disease)
  • All acute toxic effects of any prior treatment have resolved to NCI-CTCAE v 4.0 Grade 1 or less (except alopecia) at the time of signing the Informed Consent Form (ICF)
Show all 13Show fewer
  • Subject must be able to swallow and retain oral medication
  • At least one site of measurable disease on x-ray/CT/MRI scan as defined by RECIST 1.1
  • Adequate organ function within 14 days of registration
  • Written, voluntary informed consent
  • Fertile men and women of childbearing potential must agree to use an effective method of birth control from Day 1 of study and for 3 months after last study drug administration in both sexes, as assessed by the investigator. Women of childbearing potential include pre-menopausal women and women within the first 2 years of the onset of menopause. Women of childbearing potential must have a negative pregnancy test less than or equal to seven days prior to Day 1 of study. The definition of adequate contraception will be based on the judgement of the investigator.
  • Evidence of progression of disease as defined by RECIST 1.1 (i.e. new disease sites or 20% growth of index lesions) within 6 months of registration
  • Patients with central nervous system disease are eligible for enrollment if they have received prior radiotherapy or surgery to sites of CNS (central nervous system) metastatic disease and are without evidence of clinical progression for at least 12 weeks after therapy

Who cannot join

  • Patients with documentation of well differentiated liposarcoma only (of the well differentiated/dedifferentiated liposarcoma family) are specifically excluded, owing to its characteristically slow growth. If high grade areas are suspected (dedifferentiation), but not proved by pathology analysis (e.g. after primary resection of a well-differentiated liposarcoma), a biopsy must be performed to demonstrate the high-grade dedifferentiated disease
  • Prior systemic therapy with a small molecule oral kinase inhibitor, including but not limited to: pazopanib, sunitinib, sorafenib, everolimus, sirolimus, vemurafenib, dasatinib and trametinib
  • Previous assignment to treatment during this study. Subjects permanently withdrawn from study participation will not be allowed to re-enter study. Patients who progress on placebo are specifically allowed to enroll on the treatment arm of the study if they meet all other entry criteria
  • Concurrent, clinically significant, active malignancies within 12 months of study enrollment
  • Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol
  • Major surgery within 28 days prior to study registration or those patients who have not recovered adequately from prior surgery
Show all 29Show fewer
  • Patients who have received wide field radiotherapy ≤ 28 days (defined as > 50% of volume of pelvis bones or equivalent) or limited field radiation for palliation < 14 days prior to study registration or those patients who have not recovered adequately from side effects of such therapy
  • Patients who have received prior systemic therapy < 14 days prior to study registration or have not recovered adequately from toxicities to CTCAE v. 4.03 grade 1 or less; prior investigational therapy may not have been given < 5 half-lives of last dose of treatment, or < 14 days, whichever is greater
  • Patients who have had prior autologous, or allogeneic bone marrow transplant
  • Uncontrolled hypertension (systolic pressure >140 mm Hg or diastolic pressure > 90 mm Hg [NCI-CTCAE v 4.0] on repeated measurement) despite optimal medical management
  • Active or clinically significant cardiac disease including: Congestive heart failure-New York Heart Association (NYHA) > class II, Active coronary artery disease, Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin, Unstable angina (anginal symptoms at rest), new onset angina within 3 months before randomization, or myocardial infarction within 6 months before randomization
  • Evidence or history of bleeding diathesis
  • Any hemorrhage or bleeding event ≥ NCI CTCAE Grade 3 within 4 weeks prior to study registration
  • Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks) deep vein thrombosis or pulmonary embolism within 6 months of start of study treatment
  • Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy.
  • Ongoing infection > Grade 2 NCI-CTCAE v 4.03
  • Presence of a non-healing wound, non-healing ulcer, or benign bone fracture (patients with stress insufficiency fractures e.g. from osteoporosis or pathological fracture from tumor are eligible for study)
  • Patients with seizure disorder requiring medication
  • Proteinuria > 100 mg/dl on urine analysis
  • Interstitial lung disease with ongoing signs and symptoms at the time of informed consent
  • Pleural effusion or ascites that causes respiratory compromise (≥ NCI-CTCAE version 4.03 Grade 2 dyspnea)
  • History of organ allograft (including corneal transplant).
  • Known or suspected allergy or hypersensitivity to regorafenib, or excipients of the formulations given during the course of this trial
  • Any malabsorption condition.
  • Women who are pregnant or breast-feeding.
  • Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation
  • Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results
  • Inability to comply with protocol required procedures
  • Use of any herbal remedy (e.g. St. John wort [Hypericum perforatum])

Trial locations and contacts

18 sites in 1 country.

18 sites in 1 country

United States18 sites

  • Dana Farber/Partners Cancer Care

    Boston, Massachusetts, 02215

  • Carolinas Healthcare System

    Charlotte, North Carolina, 28203

  • Northwestern University

    Chicago, Illinois, 60611

  • Ohio State University

    Columbus, Ohio, 43202

  • City of Hope National Medical Center

    Duarte, California, 91010

  • Duke University

    Durham, North Carolina, 27705

  • Texas Children's Hospital

    Houston, Texas, 77030

  • Indiana University

    Indianapolis, Indiana, 46202

  • Mayo Clinic - Florida

    Jacksonville, Florida, 32224

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • Vanderbilt University

    Nashville, Tennessee, 37232

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Mayo Clinic - Minnesota

    Rochester, Minnesota, 55905

  • Huntsman Cancer Institute

    Salt Lake City, Utah, 84112

  • Sarcoma Oncology Research Center

    Santa Monica, California, 90403

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98109

  • Stanford University

    Stanford, California, 94305

  • H. Lee Moffitt

    Tampa, Florida, 33612

Other trials in United States

About this study

Although regorafenib was approved for use in patients who had progressive GIST despite imatinib and/or sunitinib on the basis of phase II and phase III data, it has not been examined in a systematic fashion in patients with other forms of sarcoma.

Given the activity of sorafenib, sunitinib and pazopanib in soft tissue sarcomas, and evidence of activity of sorafenib in osteogenic sarcoma and possibly Ewing/Ewing-like sarcoma, there is precedent to examine SMOKIs (small molecule oral kinase inhibitors) such as regorafenib in sarcomas other than GIST. It is also recognized that SMOKIs (small molecule oral kinase inhibitors)such as regorafenib, sorafenib, pazopanib, and sunitinib have overlapping panels of kinases that are inhibited simultaneously. While not equivalent, most of these SMOKIs (small molecule oral kinase inhibitors) block vascular endothelial growth factor and platelet derived growth factors receptors (VEGFRs and PDGFRs), speaking to a common mechanism of action of several of these agents.

Read the detailed description

Although regorafenib was approved for use in patients who had progressive GIST despite imatinib and/or sunitinib on the basis of phase II and phase III data, it has not been examined in a systematic fashion in patients with other forms of sarcoma.

Given the activity of sorafenib, sunitinib and pazopanib in soft tissue sarcomas, and evidence of activity of sorafenib in osteogenic sarcoma and possibly Ewing/Ewing-like sarcoma, there is precedent to examine SMOKIs (small molecule oral kinase inhibitors) such as regorafenib in sarcomas other than GIST. It is also recognized that SMOKIs (small molecule oral kinase inhibitors)such as regorafenib, sorafenib, pazopanib, and sunitinib have overlapping panels of kinases that are inhibited simultaneously. While not equivalent, most of these SMOKIs (small molecule oral kinase inhibitors) block vascular endothelial growth factor and platelet derived growth factors receptors (VEGFRs and PDGFRs), speaking to a common mechanism of action of several of these agents

Being tested
Regorafenib, Placebo
Medical subject headings
Liposarcoma, Osteosarcoma, Rhabdomyosarcoma, Chondrosarcoma, Mesenchymal

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RegorafenibDrug

    Adults: 160 mg daily; 21 days on and 7 days off Pediatrics: 82mg/m2 (rounding to the nearest 20mg) daily; 21 days on and 7 days off

  • PlaceboDrug

    21 days on and 7 days off

Study groups in NCT02048371
Study groupRoleWhat they receive
Cohort A: LiposarcomaActive comparatorAdults: 160 mg daily; 21 days on and 7 days off Pediatrics: 82mg/m2 (rounding to the nearest 20mg) daily; 21 days on and 7 days off Regorafenib
Receives: Drug: Regorafenib
Cohort A: Liposarcoma, PlaceboPlacebo comparator21 days on and 7 days off Placebo
Receives: Drug: Placebo
Cohort B: OsteosarcomaActive comparatorAdults: 160 mg daily; 21 days on and 7 days off Pediatrics: 82mg/m2 (rounding to the nearest 20mg) daily; 21 days on and 7 days off Regorafenib
Receives: Drug: Regorafenib
Cohort B: Osteosarcoma, placeboPlacebo comparator21 days on and 7 days off Placebo
Receives: Drug: Placebo
Cohort C: Ewing sarcomaActive comparatorAdults: 160 mg daily; 21 days on and 7 days off Pediatrics: 82mg/m2 (rounding to the nearest 20mg) daily; 21 days on and 7 days off Regorafenib
Receives: Drug: Regorafenib
Cohort D: RhabdomyosarcomaActive comparatorAdults: 160 mg daily; 21 days on and 7 days off Pediatrics: 82mg/m2 (rounding to the nearest 20mg) daily; 21 days on and 7 days off Regorafenib
Receives: Drug: Regorafenib
Cohort E: Mesenchymal ChondrosarcomaActive comparatorAdults: 160 mg daily; 21 days on and 7 days off Pediatrics: 82mg/m2 (rounding to the nearest 20mg) daily; 21 days on and 7 days off Regorafenib
Receives: Drug: Regorafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival (PFS). Cohort A and Cohort B

    The progression-free survival is the length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse. Cohort A (liposarcoma) and Cohort B (osteosarcoma). PFS will be evaluated according to RECIST (Response Evaluation Criteria In Solid Tumors) 1.1, where a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

    Measured: up to 3 years

  2. Progression-free Survival (PFS). Cohort C, Cohort D, and Cohort E

    The progression-free survival is the length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse. Cohort C (Ewing/Ewing-like sarcoma). PFS will be evaluated according to RECIST (Response Evaluation Criteria In Solid Tumors) 1.1.

    Measured: up to 16 weeks

Secondary outcomes (7)

  1. The Number of Participants With Reported CTCAE (Common Terminology Criteria for Adverse Events) Version 4.03 Adverse Events. All Cohorts.

    Common Toxicity Criteria, also referred to as the Common Terminology Criteria for Adverse Events (CTCAE), is a standardized classification of side effects used in assessing drugs for cancer therapy. Cohorts A, B, C, and D.

    Measured: up to 3 years

  2. Overall Response Rate (ORR). All Cohorts.

    The overall response rate (ORR) is the percentage of patients whose cancer shrinks or disappears after treatment. ORR will be evaluated according to RECIST (Response Evaluation Criteria In Solid Tumors) 1.1

    Measured: up to 3 years

  3. Progression-free Survival (PFS), Cohorts A and B, After Crossover.

    The progression-free survival is the length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse.

    Measured: up to 3 years

  4. Response Rate (RR), Cohorts A and B, After Crossover.

    The response rate (RR) is the percentage of patients whose cancer shrinks or disappears after treatment.

    Measured: up to 3 years

  5. Time to Tumor Progression (TTP), Cohorts A and B, After Crossover.

    Time to tumor progression (TTP) is the length of time from the date of diagnosis or the start of treatment for a disease until the disease starts to get worse or spread to other parts of the body.

    Measured: up to 3 years

  6. Overall Survival (OS). Cohorts A and B, After Crossover.

    Overall survival (OS) is the length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, that patients diagnosed with the disease are still alive.

    Measured: up to 3 years

  7. Disease Specific Survival (DSS). Cohorts A and B, After Crossover.

    Disease-specific survival refers to the percentage of people in a study or treatment group who have not died from a specific disease in a defined period of time.

    Measured: up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jan 2014 (estimated)
  2. Study startJul 2014
  3. Primary completionMay 2022
  4. Study completionMay 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
131 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02048371
Sponsor's protocol ID
SARC024
Status last verified
Oct 2023
First submitted
10 Jan 2014
Last updated
7 Nov 2023
Data monitoring committee
Yes

Publications

  • Riedel RF, Ballman KV, Lu Y, Attia S, Loggers ET, Ganjoo KN, Livingston MB, Chow W, Wright J, Ward JH, Rushing D, Okuno SH, Reed DR, Liebner DA, Keedy VL, Mascarenhas L, Davis LE, Ryan C, Reinke DK, Maki RG. A Randomized, Double-Blind, Placebo-Controlled, Phase II Study of Regorafenib Versus Placebo in Advanced/Metastatic, Treatment-Refractory Liposarcoma: Results from the SARC024 Study. Oncologist. 2020 Nov;25(11):e1655-e1662. doi: 10.1634/theoncologist.2020-0679. Epub 2020 Aug 20.

    PubMed 32701199

  • Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.

    PubMed 31401903

  • Davis LE, Bolejack V, Ryan CW, Ganjoo KN, Loggers ET, Chawla S, Agulnik M, Livingston MB, Reed D, Keedy V, Rushing D, Okuno S, Reinke DK, Riedel RF, Attia S, Mascarenhas L, Maki RG. Randomized Double-Blind Phase II Study of Regorafenib in Patients With Metastatic Osteosarcoma. J Clin Oncol. 2019 Jun 1;37(16):1424-1431. doi: 10.1200/JCO.18.02374. Epub 2019 Apr 23.

    PubMed 31013172

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Regorafenib in people with Liposarcoma and Osteogenic Sarcoma, run by Sarcoma Alliance for Research through Collaboration at 18 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (PFS). Cohort A and Cohort B (time frame: up to 3 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02048371, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Nov 2023.

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