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

Plain English Summary

Combination Chemotherapy With or Without Ganitumab in Treating Patients With Newly Diagnosed Metastatic Ewing Sarcoma is a Phase 3 clinical trial sponsored by National Cancer Institute (NCI) studying 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. Tests the effectiveness of adding ganitumab to chemotherapy for treating newly diagnosed metastatic Ewing sarcoma. For patients with metastatic Ewing sarcoma, aged 1 month and older, who have not had prior treatment. Participation involves receiving chemotherapy and possibly ganitumab, with regular check-ups and tests. Alternative treatments include standard chemotherapy without ganitumab. The trial aims to enroll 312 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible patients are those with newly diagnosed metastatic Ewing sarcoma, aged 1 month and older, with adequate tumor tissue. Exclusions include patients with prior treatment for Ewing sarcoma, those with severe organ dysfunction, and those with certain blood sugar levels. Age: 1 month and older. Health: Good overall health, with specific criteria for kidney and liver function. This trial is studying 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, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures the event-free survival of patients, which means how long they can stay free from disease progression or recurrence. The specific primary outcome measures are: Event-free Survival (5 years after enrollment). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial aims to fill a treatment gap by evaluating a new drug that may improve outcomes for patients with metastatic Ewing sarcoma. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets 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, where improved treatment options are needed.

Investor Insight

The market size for pediatric oncology treatments is significant, with this trial potentially leading to a new standard of care. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor if you have any other health conditions that might affect your participation. Participation involves regular check-ups, blood tests, and imaging scans. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 312 participants

Interventions

• DRUG: Cyclophosphamide — Given IV
• DRUG: Doxorubicin — Given IV
• DRUG: Doxorubicin Hydrochloride — Given IV
• DRUG: Etoposide — Given IV
• DRUG: Etoposide Phosphate — Given IV

Primary Outcomes

• Event-free Survival (5 years after enrollment)

Secondary Outcomes

• Overall Survival (5 years after enrollment)
• Frequency of Toxicity-events (Up to 202 days)

Full 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 (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

Trial Locations

• Children's Hospital of Alabama, Birmingham, Alabama, United States
• USA Health Strada Patient Care Center, Mobile, Alabama, United States
• Providence Alaska Medical Center, Anchorage, Alaska, United States
• Banner Children's at Desert, Mesa, Arizona, United States
• Phoenix Childrens Hospital, Phoenix, Arizona, United States
• Banner University Medical Center - Tucson, Tucson, Arizona, United States
• Onvida Health Yuma Medical Center, Yuma, Arizona, United States
• CHI Saint Vincent Cancer Center Hot Springs, Hot Springs, Arkansas, United States
• Arkansas Children's Hospital, Little Rock, Arkansas, United States
• Kaiser Permanente Downey Medical Center, Downey, California, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Related conditions include other types of bone and soft tissue sarcomas.
• Therapeutic areas include oncology, specifically pediatric and adolescent oncology.

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