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NCT02048371 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE2
Status at capture
COMPLETED
Registry last update
2023-11-07

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

Overall Response Rate (ORR). All Cohorts.

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
Inclusion Criteria: * 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) * 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 Exclusion Criteria: * 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 * 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 \[Hypericum perforatum\])
healthy Volunteers
false
minimum Age
5 Years
sex
ALL
std Ages
  1. CHILD
  2. ADULT
  3. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    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 Regorafenib
    intervention Names
    1. Drug: Regorafenib
    label
    Cohort A: Liposarcoma
    type
    ACTIVE_COMPARATOR
  2. description
    21 days on and 7 days off Placebo
    intervention Names
    1. Drug: Placebo
    label
    Cohort A: Liposarcoma, Placebo
    type
    PLACEBO_COMPARATOR
  3. description
    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 Regorafenib
    intervention Names
    1. Drug: Regorafenib
    label
    Cohort B: Osteosarcoma
    type
    ACTIVE_COMPARATOR
  4. description
    21 days on and 7 days off Placebo
    intervention Names
    1. Drug: Placebo
    label
    Cohort B: Osteosarcoma, placebo
    type
    PLACEBO_COMPARATOR
  5. description
    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 Regorafenib
    intervention Names
    1. Drug: Regorafenib
    label
    Cohort C: Ewing sarcoma
    type
    ACTIVE_COMPARATOR
  6. description
    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 Regorafenib
    intervention Names
    1. Drug: Regorafenib
    label
    Cohort D: Rhabdomyosarcoma
    type
    ACTIVE_COMPARATOR
  7. description
    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 Regorafenib
    intervention Names
    1. Drug: Regorafenib
    label
    Cohort E: Mesenchymal Chondrosarcoma
    type
    ACTIVE_COMPARATOR
interventions
  1. arm Group Labels
    1. Cohort A: Liposarcoma
    2. Cohort B: Osteosarcoma
    3. Cohort C: Ewing sarcoma
    4. Cohort D: Rhabdomyosarcoma
    5. Cohort E: Mesenchymal Chondrosarcoma
    description
    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
    name
    Regorafenib
    type
    DRUG
  2. arm Group Labels
    1. Cohort A: Liposarcoma, Placebo
    2. Cohort B: Osteosarcoma, placebo
    description
    21 days on and 7 days off
    name
    Placebo
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
CROSSOVER
masking Info
masking
TRIPLE
who Masked
  1. PARTICIPANT
  2. CARE_PROVIDER
  3. INVESTIGATOR
primary Purpose
TREATMENT
Enrollment
count
131
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    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.
    measure
    Progression-free Survival (PFS). Cohort A and Cohort B
    time Frame
    up to 3 years
  2. description
    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.
    measure
    Progression-free Survival (PFS). Cohort C, Cohort D, and Cohort E
    time Frame
    up to 16 weeks
secondary Outcomes
  1. description
    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.
    measure
    The Number of Participants With Reported CTCAE (Common Terminology Criteria for Adverse Events) Version 4.03 Adverse Events. All Cohorts.
    time Frame
    up to 3 years
  2. description
    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
    measure
    Overall Response Rate (ORR). All Cohorts.
    time Frame
    up to 3 years
  3. description
    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.
    measure
    Progression-free Survival (PFS), Cohorts A and B, After Crossover.
    time Frame
    up to 3 years
  4. description
    The response rate (RR) is the percentage of patients whose cancer shrinks or disappears after treatment.
    measure
    Response Rate (RR), Cohorts A and B, After Crossover.
    time Frame
    up to 3 years
  5. description
    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.
    measure
    Time to Tumor Progression (TTP), Cohorts A and B, After Crossover.
    time Frame
    up to 3 years
  6. description
    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.
    measure
    Overall Survival (OS). Cohorts A and B, After Crossover.
    time Frame
    up to 3 years
  7. description
    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.
    measure
    Disease Specific Survival (DSS). Cohorts A and B, After Crossover.
    time Frame
    up to 3 years
Full study description
brief 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. 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.
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
Source references
references
  1. citation
    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.
    pmid
    32701199
    type
    DERIVED
  2. citation
    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.
    pmid
    31401903
    type
    DERIVED
  3. citation
    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.
    pmid
    31013172
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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      occurrences
      1. context exact
        kinase inhibitors.</strong> <div class="pdq-content-list"><ul id="_2481"><li><strong>Regorafenib:</strong> A phase II study (<a href="/clinicaltrials/NCT02048371">SARC024 [NCT02048371]</a>) evaluated regorafenib monotherapy in 30 patients with metastatic recurrent Ewing sarcoma and other translocation-positive tumors,
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      2. context exact
        rong> <div class="pdq-content-list"><ul id="_2481"><li><strong>Regorafenib:</strong> A phase II study (<a href="/clinicaltrials/NCT02048371">SARC024 [NCT02048371]</a>) evaluated regorafenib monotherapy in 30 patients with metastatic recurrent Ewing sarcoma and other translocation-positive tumors, including <em class="g
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      source title
      Ewing Sarcoma and Undifferentiated Small Round Cell Sarcomas of Bone and Soft Tissue Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: November 27, 2024
        datetime
        2024-11-27T12:00:00Z
        display
        November 27, 2024

    Preserved source evidence · Not medical advice