Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

SARC024: A Blanket Protocol to Study Oral Regorafenib in Patients With Refractory Liposarcoma, Osteogenic Sarcoma, and Ewing Sarcomas

Protocol: OSU-14056

Full Title

SARC024: A blanket protocol to study oral regorafenib in patients with refractory liposarcoma, osteogenic sarcoma, and Ewing/Ewing like sarcomas

Purpose

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 Objective

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

Are you eligible?

Inclusion Criteria:

Patients 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.

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. Baseline imaging must be performed within 28 days of Day 1 of study.

Adequate organ function within 14 days of registration INR (International Normalized

Ratio) : patients with no prior evidence of underlying abnormality in coagulation

parameters exists, according to the written documentation of the treating physician

Evidence of progression of disease as defined by RECIST 1.1 (i.e. new disease sites

or 30% 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.

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. 4.0 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.

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

randomization3.2.11

Evidence or history of bleeding diathesis or coagulopathy

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 4.0

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

Persistent proteinuria: Grade 3 NCI-CTCAE v 4.0 (> 3.5 g/24 h, measured by urine

protein:creatinine ratio on a random urine sample)

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

4.0 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]).