Clinical Trial 17904

Cancer Type: Sarcoma
Interventions:BAY 73-4506 (Regorafenib); Placebo; Regorafenib

Study Type: Treatment
Phase of Study: Phase II
Investigators:


    Overview

    Study Title

    SARC024: A Blanket Protocol to Study Oral Regorafenib in Patients with Refractory Liposarcoma, Osteogenic Sarcoma, and Ewing/Ewing-Like Sarcomas

    Summary

    The purpose of this study is to find out if an investigational drug called regorafenib can help people with sarcoma. Regorafenib is approved in the United States to treat colon cancer and one form of sarcoma (GIST), but we do not know if regorafenib is useful to treat people with liposarcoma, osteosarcoma, and Ewing / Ewing-like sarcomas.

    Objective

    Primary Objective: A. Cohort A (liposarcoma): To compare the progression-free survival (PFS) of eligible subjects treated with regorafenib or placebo according to modified RECIST version 1.1. B. Cohort B (osteogenic sarcoma): To compare the progression-free survival (PFS) of eligible subjects treated with regorafenib or placebo according to RECIST version 1.1. C. Cohort C (Ewing/Ewing-like sarcoma): To estimate the RECIST 1.1 PFS rate of eligible subjects treated with regorafenib at 8 and 16 weeks. Secondary Objectives: A. All cohorts: Calculate the incidence of reported CTCAE v 4.0 adverse events and abnormal laboratory test results. B. All cohorts: Estimate the overall response rate (ORR) per RECIST version 1.1, time to tumor progression (TTP), PFS (12 weeks), overall survival (OS), disease specific survival (DSS). C. Cohort A & B, after crossover: Assess PFS, RR, TTP, OS, and DSS following administration of regorafenib in the open label portion of the study. Exploratory Objectives: A. Assess PFS and RR in these populations by Choi criteria. B. Growth modulation index for treatment with regorafenib vs. prior line of therapy, defined as TTPregorafenib/TTPprior.

    Inclusion Criteria

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  • Must have histologically or cytologically confirmed advanced/metastatic liposarcoma, osteogenic sarcoma, or Ewing/Ewing-like sarcoma of soft tissue or bone. This study will accept the diagnosis made at the investigator's center.
  • Age 18 years or older.
  • World Health Organization (WHO) Performance Status 0, 1 or 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 4.03 Grade 1 or less (except alopecia, Grade 0-2 permitted, and anemia, grade 0-2 permitted) at the time of signing the Informed Consent Form (ICF).
  • 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. Baseline imaging must be performed within 28 days of first study drug administration.
  • Adequate organ function within 14 days of registration.
  • Evidence of progression of disease as defined by RECIST 1.1 (i.e. new disease sites or 20% growth of target 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

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  • 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).
  • Prior systemic therapy with a small molecule oral kinase inhibitor.
  • Previous assignment to treatment during this study. Participants 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.
  • 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.
  • Have received wide field radiotherapy ≤ 28 days or limited field radiation for palliation > Have received prior systemic therapy > Uncontrolled hypertension.
  • Active or clinically significant cardiac disease.
  • Evidence or history of bleeding diathesis. Patients on warfarin, heparinoids, or factor X inhibitors are permitted on study.
  • Any hemorrhage or bleeding event ≥ NCI CTCAE Grade 3 within 4 weeks prior to study registration.
  • Potential participants 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).
  • Seizure disorder requiring medication.
  • No 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 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]).