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

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ClinicalTrials.gov Identifier: NCT02048371
Recruitment Status : Recruiting
First Posted : January 29, 2014
Last Update Posted : August 10, 2021
Sponsor:
Information provided by (Responsible Party):
Sarcoma Alliance for Research through Collaboration

Tracking Information
First Submitted Date  ICMJE January 10, 2014
First Posted Date  ICMJE January 29, 2014
Last Update Posted Date August 10, 2021
Actual Study Start Date  ICMJE July 2014
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 8, 2020)
  • Progression-free survival (PFS). Cohort A [ Time Frame: up to 3 years ]
    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). PFS will be evaluated according to RECIST (Response Evaluation Criteria In Solid Tumors) 1.1.
  • Progression-free survival (PFS). Cohort B [ Time Frame: up to 3 years ]
    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 B (osteogenic sarcoma). PFS will be evaluated according to RECIST (Response Evaluation Criteria In Solid Tumors) 1.1.
  • Progression-free survival (PFS). Cohort C [ Time Frame: up to 16 weeks ]
    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.
  • Progression-free survival (PFS). Cohort D [ Time Frame: up to 16 weeks ]
    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 D (Rhabdomyosarcoma). PFS will be evaluated according to RECIST (Response Evaluation Criteria In Solid Tumors) 1.1.
  • Progression-free survival (PFS). Cohort E [ Time Frame: up to 16 weeks ]
    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 E (Mesenchymal Chondrosarcoma). PFS will be evaluated according to RECIST (Response Evaluation Criteria In Solid Tumors) 1.1.
Original Primary Outcome Measures  ICMJE
 (submitted: January 27, 2014)
  • The progression-free survival (PFS) [ Time Frame: up to 3 years ]
    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 (osteogenic sarcoma). PFS will be evaluated according to RECIST (Response Evaluation Criteria In Solid Tumors) 1.1
  • The progression-free survival (PFS) [ Time Frame: up to 16 weeks ]
    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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 30, 2020)
  • The incidence of reported CTCAE (Common Terminology Criteria for Adverse Events) version 4.03 adverse events. All cohorts. [ Time Frame: up to 3 years ]
    Common Toxicity Criteria, also referred to as the Common Terminology Criteria for Adverse Events (CTCAE), is a standardised classification of side effects used in assessing drugs for cancer therapy. Cohorts A, B, C, and D.
  • Overall response rate (ORR). All cohorts. [ Time Frame: up to 3 years ]
    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
  • Progression-free survival (PFS), Cohorts A and B, after crossover. [ Time Frame: up to 3 years ]
    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.
  • Response rate (RR), Cohorts A and B, after crossover. [ Time Frame: up to 3 years ]
    The response rate (RR) is the percentage of patients whose cancer shrinks or disappears after treatment.
  • Time to tumor progression (TTP), Cohorts A and B, after crossover. [ Time Frame: up to 3 years ]
    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.
  • overall survival (OS). Cohorts A and B, after crossover. [ Time Frame: up to 3 years ]
    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.
  • Disease Specific Survival (DSS). Cohorts A and B, after crossover. [ Time Frame: up to 3 years ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 27, 2014)
  • The incidence of reported CTCAE (Common Terminology Criteria for Adverse Events) version 4.0 [ Time Frame: up to 3 years ]
    Common Toxicity Criteria, also referred to as the Common Terminology Criteria for Adverse Events (CTCAE), is a standardised classification of side effects used in assessing drugs for cancer therapy. Cohorts A, B and C. PFS will be evaluated according to RECIST (Response Evaluation Criteria In Solid Tumors) 1.1
  • Overall response rate (ORR) [ Time Frame: up to 3 years ]
    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
  • Time to tumor progression (TTP) [ Time Frame: up to 3 years ]
    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. TTP will be evaluated according to RECIST (Response Evaluation Criteria In Solid Tumors) 1.1
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE SARC024: A Blanket Protocol to Study Oral Regorafenib in Patients With Selected Sarcoma Subtypes
Official Title  ICMJE SARC024: A Blanket Protocol to Study Oral Regorafenib in Patients With Selected Sarcoma Subtypes
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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Liposarcoma
  • Osteogenic Sarcoma
  • Ewing/Ewing-like Sarcoma
  • Rhabdomyosarcoma
  • Mesenchymal Chondrosarcoma
Intervention  ICMJE
  • Drug: Regorafenib
    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
  • Drug: Placebo
    21 days on and 7 days off
Study Arms  ICMJE
  • Active Comparator: Cohort A: Liposarcoma

    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: Drug: Regorafenib
  • Placebo Comparator: Cohort A: Liposarcoma, Placebo

    21 days on and 7 days off

    Placebo

    Intervention: Drug: Placebo
  • Active Comparator: Cohort B: Osteosarcoma

    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: Drug: Regorafenib
  • Placebo Comparator: Cohort B: Osteosarcoma, placebo

    21 days on and 7 days off

    Placebo

    Intervention: Drug: Placebo
  • Active Comparator: Cohort C: Ewing sarcoma

    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: Drug: Regorafenib
  • Active Comparator: Cohort D: Rhabdomyosarcoma

    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: Drug: Regorafenib
  • Active Comparator: Cohort E: Mesenchymal Chondrosarcoma

    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: Drug: Regorafenib
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 19, 2018)
150
Original Enrollment  ICMJE Not Provided
Estimated Study Completion Date  ICMJE February 2022
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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])
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 5 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: SARC Office 734-930-7600 sarc@sarctrials.org
Contact: SARC Office 734-930-7600 sarc024@sarctrials.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02048371
Other Study ID Numbers  ICMJE SARC024
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sarcoma Alliance for Research through Collaboration
Study Sponsor  ICMJE Sarcoma Alliance for Research through Collaboration
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Robert Maki, MD, PhD University of Pennsylvania
PRS Account Sarcoma Alliance for Research through Collaboration
Verification Date August 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP