AEWS1221: Randomized Phase 3 Trial Evaluating the Addition of the IGF-1R Monoclonal Antibody Ganitumab (AMG 479, NSC# 750008) to Multiagent Chemotherapy for Patients With Newly Diagnosed Metastatic Ewing Sarcoma

Investigator: Julio Barredo

Institutional Protocol #: 20170458

National Clinical Trials Identifier: NCT02306161

Funding Agency/Sponsor: COG

Division: Cancer Center

Therapeutic Area: Pediatric Cancer

Phase: Phase III

Enrolling Sites: University of Miami Medical Group, University of Miami Hospital & Clinics, Jackson Memorial Hospital

Enrolling Since: 9/1/2017


Purpose/Abstract:


This randomized phase III trial studies how well combination chemotherapy with or without
ganitumab works in treating patients with newly diagnosed Ewing sarcoma that has spread to
other parts of the body. Monoclonal antibodies, such as ganitumab, may block tumor growth in
different ways by targeting certain cells. Drugs used in chemotherapy, such as vincristine
sulfate, doxorubicin hydrochloride, cyclophosphamide, ifosfamide, and etoposide, work in
different ways to stop the growth of tumor cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. It is not yet known whether
combination chemotherapy is more effective with or without ganitumab in treating patients
with newly diagnosed Ewing sarcoma.




Eligibility Criteria:


Inclusion Criteria:

- Patients with histologic diagnosis (by institutional pathologist) of newly diagnosed
Ewing sarcoma or peripheral primitive neuroectodermal tumor (PNET) arising from bone
or soft tissue and with metastatic disease involving lung, bone, bone marrow, or other
metastatic site

- For the purpose of this study metastatic disease is defined as one or more of the
following:

- Lesions which are discontinuous from the primary tumor, are not regional lymph
nodes, and do not share a bone or body cavity with the primary tumor; skip
lesions in the same bone as the primary tumor do not constitute metastatic
disease; skip lesions in an adjacent bone are considered bone metastases; if
there is any doubt whether lesions are metastatic, a biopsy of those lesions
should be performed

- Contralateral pleural effusion and/or contralateral pleural nodules

- Distant lymph node involvement

- Patients with pulmonary nodules are considered to have metastatic disease if the
patient has:

- Solitary nodule >= 0.5 cm or multiple nodules of >= 0.3 cm unless lesion is
biopsied and negative for tumor

- Patients with solitary nodule < 0.5 cm or multiple nodules < 0.3 cm are not
considered to have lung metastasis unless biopsy documents tumor

- Bone marrow metastatic disease is based on morphologic evidence of Ewing sarcoma
based on hematoxylin and eosin (H&E) stains; in the absence of morphologic
evidence of marrow involvement on H&E, patients with bone marrow involvement
detected ONLY by flow cytometry, reverse-transcriptase (RT)-polymerase chain
reaction (PCR), fluorescence in situ hybridization (FISH), or
immunohistochemistry will NOT be considered to have clinical bone marrow
involvement for the purposes of this study

- This study requires bilateral bone marrow biopsies at study entry; the
suggested approach for patients with large pelvic tumors in which a
posterior iliac crest bone marrow biopsy would track through the tumor is to
instead undergo 2 marrow biopsies on the contralateral side (either 2
posterior biopsies or one posterior and one anterior biopsy)

- Bone metastasis: This study utilizes whole body FDG-PET scans to screen patients
for bone metastases; areas suspicious for bone metastasis based on FDG-PET scans
require confirmatory anatomic imaging with either MRI or computed tomography (CT)
(whole body FDG-PET/CT or FDG-PET/magnetic resonance [MR] scan acceptable); whole
body technetium bone scans may be performed at the discretion of the investigator
and are not required; for patients without other sites of metastatic disease
whose sole metastatic site to qualify for study entry is a single area suspicious
for bone metastasis identified by FDG-PET, confirmatory biopsy or anatomic
imaging evidence of an associated soft tissue mass at that site is required for
study entry

- Patients must have adequate tumor tissue to meet the minimum requirement for
submission

- Enrolling institutions are reminded that submission of pre-treatment serum, tumor
tissue and whole blood is required

- Patients should only have had a biopsy of the primary tumor without an attempt at
complete or partial resection; patients will still be eligible if excision was
attempted or accomplished as long as adequate anatomic imaging (MRI for most primary
tumor sites) was obtained prior to surgery

- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

- Age < 6 months: Maximum serum creatinine (mg/dL): 0.4 for males and females

- Age 6 months to < 1 year: Maximum serum creatinine (mg/dL): 0.5 for males and
females

- Age 1 to < 2 years: Maximum serum creatinine (mg/dL): 0.6 for males and females

- Age 2 to < 6 years: Maximum serum creatinine (mg/dL): 0.8 for males and females

- Age 6 to < 10 years: Maximum serum creatinine (mg/dL): 1 for males and females

- Age 10 to < 13 years: Maximum serum creatinine (mg/dL): 1.2 for males and females

- Age 13 to < 16 years: Maximum serum creatinine (mg/dL): 1.5 for males and 1.4 for
females

- Age >= 16 years: Maximum serum creatinine (mg/dL): 1.7 for males and 1.4 for
females

- Total bilirubin =< 1.5 x upper limit of normal (ULN) for age, and

- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 3 x
upper limit of normal (ULN) for age (except for patients with liver metastasis who may
enroll if ALT < 5 times ULN for age)

- Shortening fraction of >= 27% or

- Ejection fraction of >= 50%

- Patients must have a normal blood sugar level for age to participate; if an initial
random draw (ie. non-fasting) blood glucose value is out of range, it is acceptable to
repeat this test as a fasting draw

- All patients and/or their parents or legal guardians must sign a written informed
consent

- All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met

Exclusion Criteria:

- Patients with regional node involvement as their only site of disease beyond the
primary tumor will not be eligible

- Patients whose primary tumors arise in the intra-dural soft tissue (eg. brain and
spinal cord) are not eligible

- Patients who have received prior chemotherapy or radiation therapy are not eligible

- Female patients of childbearing potential are not eligible unless a negative pregnancy
test result has been obtained; lactating females are not eligible unless they have
agreed not to breastfeed their infants for the duration of protocol therapy; sexually
active patients of reproductive potential are not eligible unless they have agreed to
use an effective contraceptive method for the duration of protocol therapy

- Patients with known pre-existing diabetes mellitus will be excluded from study

- Patients receiving chronic pharmacologic doses of corticosteroids are not eligible;
for the purposes of eligibility, chronic exposure is defined as anticipated exposure
of > 3 weeks, including the sum of both pre-enrollment and anticipated post-enrollment
dosing; patients on acute corticosteroid therapy (=< 3 weeks of total planned
exposure) must still meet the normal blood glucose requirement; patients receiving
chronic inhaled corticosteroids or chronic physiologic replacement doses of
corticosteroids are eligible


Gender: All

Minimum Age: N/A

Maximum Age: 50 Years

Accepts healthy volunteers: No

Please note that this is written for scientific review, and if there are any questions or clarifications needed, please contact

Cancer Center Studies
1-866-574-5124

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