Trial record 1 of 1 for:
aews1221
Combination Chemotherapy With or Without Ganitumab in Treating Patients With Newly Diagnosed Metastatic Ewing Sarcoma
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| ClinicalTrials.gov Identifier: NCT02306161 |
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Recruitment Status :
Active, not recruiting
First Posted : December 3, 2014
Results First Posted : July 1, 2022
Last Update Posted : May 23, 2023
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Sponsor:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
National Cancer Institute (NCI)
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Brief Summary:
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. Treatment with drugs that block the IGF-1R pathway, such as ganitumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as vincristine, doxorubicin, 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 adding ganitumab to combination chemotherapy is more effective in treating patients with newly diagnosed metastatic Ewing sarcoma.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Metastatic Ewing Sarcoma Metastatic Malignant Neoplasm in the Bone Metastatic Malignant Neoplasm in the Bone Marrow Metastatic Malignant Neoplasm in the Lung Metastatic Peripheral Primitive Neuroectodermal Tumor of Bone Peripheral Primitive Neuroectodermal Tumor of Soft Tissues | Drug: Cyclophosphamide Drug: Doxorubicin Drug: Doxorubicin Hydrochloride Drug: Etoposide Drug: Etoposide Phosphate Radiation: External Beam Radiation Therapy Biological: Ganitumab Drug: Ifosfamide Radiation: Stereotactic Radiosurgery Procedure: Therapeutic Surgical Procedure Drug: Vincristine Drug: Vincristine Sulfate | Phase 3 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 312 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | 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 |
| Actual Study Start Date : | December 8, 2014 |
| Actual Primary Completion Date : | March 31, 2021 |
| Estimated Study Completion Date : | December 21, 2023 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Ewing sarcoma
MedlinePlus related topics:
Soft Tissue Sarcoma
| Arm | Intervention/treatment |
|---|---|
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Experimental: Regimen A (VDC/IE)
See Design Details.
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Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Doxorubicin Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Drug: Etoposide Given IV
Other Names:
Drug: Etoposide Phosphate Given IV
Other Name: Etopophos Radiation: External Beam Radiation Therapy Undergo EBRT
Other Names:
Drug: Ifosfamide Given IV
Other Names:
Radiation: Stereotactic Radiosurgery Undergo SBRT
Other Names:
Procedure: Therapeutic Surgical Procedure Undergo surgery Drug: Vincristine Given IV
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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Experimental: Regimen B (VDC/IE + ganitumab)
INDUCTION THERAPY: Patients receive Induction therapy as in Regimen A and receive ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 of weeks 1, 3, 5, 7, 9, and 11. LOCAL CONTROL THERAPY: Between weeks 13-18, patients undergo surgery and/or radiation therapy. CONSOLIDATION THERAPY: Patients receive Consolidation therapy as in Regimen A and receive ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 of weeks 7, 9, 11, 13, and 15. METASTATIC SITE IRRADIATION: Patients with lung metastases undergo whole lung radiation and patients with bone metastases undergo definitive SBRT or EBRT. MAINTENANCE: Patients receive ganitumab IV over 30-60 minutes or 60-120 minutes every 3 weeks for 8 cycles. |
Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Doxorubicin Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Drug: Etoposide Given IV
Other Names:
Drug: Etoposide Phosphate Given IV
Other Name: Etopophos Radiation: External Beam Radiation Therapy Undergo EBRT
Other Names:
Biological: Ganitumab Given IV
Other Names:
Drug: Ifosfamide Given IV
Other Names:
Radiation: Stereotactic Radiosurgery Undergo SBRT
Other Names:
Procedure: Therapeutic Surgical Procedure Undergo surgery Drug: Vincristine Given IV
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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Primary Outcome Measures :
- Event-free Survival [ Time Frame: 5 years after enrollment ]Estimated 5-year EFS where EFS is calculated as the time from study enrollment to disease progression, disease relapse, occurrence of a second malignant neoplasm, death from any cause or last follow-up whichever occurs first. Kaplan-Meier method is used for estimation. Patients without an event are censored at last contact.
Secondary Outcome Measures :
- Overall Survival [ Time Frame: 5 years after enrollment ]Time from study enrollment to death or last patient contact.
- Frequency of Toxicity-events [ Time Frame: Up to 202 days ]The number of induction or consolidation reporting periods in which a CTC version 4 codeable grade 4 or greater non-hematological adverse event, grade 3 or greater left ventricular systolic dysfunction or the reporting period is terminated because of a CTC codeable event.
Other Outcome Measures:
- Serum IGF Pathway Component and Tissue Protein, Deoxyribonucleic Acid (DNA), and Ribonucleic Acid Markers [ Time Frame: Up to 10 years ]In addition to the log rank test the modeling approach will be used for the primary study comparison. Linear trend in EFS-risk will be investigated by segregating the marker level according to quartiles. For bone marrow response rate analyses, Fisher's exact test will be used to compare the objective bone marrow response rate (complete response vs. incomplete response) at start of local control between patients with biomarker levels above and below the group median.
- Tumor Cell Surface IGF-1R Expression [ Time Frame: Up to 307 days ]Extent of tumor cell IGF-1R co-expression will also be reported. Change in tumor cell IGF-1R co-expression in patients treated with and without ganitumab will be reported descriptively.
- Germline Polymorphisms in EGFR [ Time Frame: Up to 10 years ]EFS will be compared between patients with and without the presence of the minor allele using the log rank test, both for the entire patient population and for patients randomized to ganitumab.
- EWS Translocation [ Time Frame: Up to 10 years ]The institutional result of EWS tumor testing will be categorized as translocation detected (yes v. no) and the type of translocation detected will also be recorded. The proportion of patients with a particular EWS translocation variant will be tabulated.
- Circulating Tumor DNA (ctDNA) Testing [ Time Frame: Up to 202 days ]Will report the proportion of patients that have a change in translocation result associated with ctDNA testing across time periods.
- Serial Genomic Profiling [ Time Frame: Up to 307 days ]Will be identified by flow cytometry. Profiles will be presented graphically, and samples obtained from different sites of tumor within the same individual will also be presented.
- Occurrence of Sinusoidal Obstructive Disease (SOS) Associated With the Addition of Ganitumab to VDC/IE [ Time Frame: Up to 202 days ]The number of induction and maintenance cycles received by patients randomized to the experimental therapy where SOS is observed. Only patients who receive all reporting period therapy or experience SOS will contribute to this outcome measure.
- Frequency of Resolution of Bone Marrow Metastases [ Time Frame: Up to 84 days ]The number of patients who are enrolled with bone marrow metastases whose bone marrow disease is not detected after evaluation at the time of of first local control measure or the end of the Induction reporting period, whichever comes first. Only eligible patients who receive at least one dose of randomized treatment assignment will be considered for this measure.
- Frequency of Toxicity Events During Ganitumab Maintenance [ Time Frame: Up to 307 days ]The number of induction or consolidation reporting periods in which a CTC version 4 codeable non-hematological adverse event, grade 3 left ventricular systolic dysfunction or the reporting period is terminated because of a CTC codeable event.
- Trough Levels of Serum Ganitumab [ Time Frame: Up to 15 days ]Trough levels of serum ganitumab prior to the second dose of ganitumab during induction obtained will be categorized as less than 10 micrograms per milliliter or greater than or equal to 10 micrograms per milliliter. This analysis will be conducted for the first 10 eligible patients who receive ganitumab.
- Proportion of Patients Who Successfully Receive Planned Stereotactic Body Radiotherapy (SBRT) [ Time Frame: 202 days ]A patient who has SBRT planned for at least one metastatic site and receives successful SBRT treatment to at least 85% of metastatic sites in the treatment plan. Successful treatment is determined by IROC review criteria. Only eligible patients start the metastatic site radiation reporting period will be considered for this outcome measure.
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| Ages Eligible for Study: | up to 50 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
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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
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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
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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
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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 (performed within 7 days prior to enrollment):
- 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 (performed within 7 days prior to enrollment), and
- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 3 x upper limit of normal (ULN) for age (performed within 7 days prior to enrollment) (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 (e.g. 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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02306161
Locations
Show 317 study locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Steven G DuBois | Children's Oncology Group |
Study Documents (Full-Text)
Documents provided by National Cancer Institute (NCI):
Documents provided by National Cancer Institute (NCI):
Study Protocol and Statistical Analysis Plan [PDF] May 1, 2019
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT02306161 |
| Other Study ID Numbers: |
NCI-2014-02380 NCI-2014-02380 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) AEWS1221 s15-00442 AEWS1221 ( Other Identifier: Children's Oncology Group ) AEWS1221 ( Other Identifier: CTEP ) U10CA180886 ( U.S. NIH Grant/Contract ) U10CA098543 ( U.S. NIH Grant/Contract ) |
| First Posted: | December 3, 2014 Key Record Dates |
| Results First Posted: | July 1, 2022 |
| Last Update Posted: | May 23, 2023 |
| Last Verified: | December 2022 |
Additional relevant MeSH terms:
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Neoplasms Sarcoma Sarcoma, Ewing Neuroectodermal Tumors Neuroectodermal Tumors, Primitive Neoplasms, Second Primary Neuroectodermal Tumors, Primitive, Peripheral Bone Neoplasms Neoplasm Metastasis Soft Tissue Neoplasms Bone Marrow Diseases Neoplasms, Connective and Soft Tissue Neoplasms by Histologic Type Osteosarcoma Neoplasms, Bone Tissue |
Neoplasms, Connective Tissue Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Neoplasms, Glandular and Epithelial Neoplasms by Site Bone Diseases Musculoskeletal Diseases Hematologic Diseases Neoplastic Processes Pathologic Processes Cyclophosphamide Ifosfamide Isophosphamide mustard Doxorubicin |