Whole-Body Radiation Therapy, Systemic Chemotherapy, and High-Dose Chemotherapy Followed By Stem Cell Rescue in Treating Patients With Poor-Risk Ewing Sarcoma

NCT01795430 | Withdrawn DMC

• 2 other identifiers: 12391NCI-2013-00439
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot clinical trial studies whole-body radiation therapy, systemic chemotherapy, and high-dose chemotherapy followed by stem cell rescue in treating patients with poor-risk Ewing sarcoma. Giving chemotherapy and radiation therapy before a peripheral blood stem cell or bone marrow transplant stops the growth of tumor cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy is given to prepare the bone marrow for stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy

Conditions

Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Ewing Sarcoma of Bone; Extraosseous Ewing Sarcoma; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor

Outcome Measures

Primary Outcomes (1)

• Percentage of patients who experience grade 4-5 non-hematologic toxicities assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

  Toxicities will be summarized as type, severity, date of onset, duration, reversibility, and attribution.

  Up to day 100 of Block II

Secondary Outcomes (4)

• Overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST)

  Up to 5 years

• Progression-free survival (PFS)

  Time from stem cell infusion to the first observation of disease progression or death from any cause, whichever occurs first, assessed up to 5 years

• Overall survival (OS)

  Time from stem cell infusion to death from any cause, assessed up to 5 years

• Non-relapse mortality (NRM)

  Time from stem cell infusion to death event where the cause of death is not attributable to the underlying disease, assessed up to 5 years

Study Arms (1)

Treatment (radiation therapy/chemotherapy, stem cell infusion)

EXPERIMENTAL

BLOCK I: Patients receive etoposide IV over 1-2 hours and ifosfamide IV over 1 hour on days 1-5. Patients also undergo WB-MRI-guided intensity-modulated radiation therapy BID, 5 days a week, for approximately 4 weeks. Patients may also undergo 4 fractions of SRT QOD, 3-8 fractions of SBRT QOD, or 10 fractions of 3D RT daily to sites of metastatic disease. BLOCK II: Patients receive high-dose chemotherapy comprising topotecan hydrochloride IV continuously over 24 hours on days -8 to -4, busulfan IV over 2 hours every 6 hours on days -8 to -4, and melphalan IV over 30 minutes on days -3 and -2. Patients undergo autologous peripheral blood or bone marrow stem cell infusion on day 0.

Drug: etoposide; Drug: ifosfamide; Radiation: intensity-modulated radiation therapy; Drug: topotecan hydrochloride; Drug: busulfan; Drug: melphalan; Procedure: autologous hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Procedure: autologous bone marrow transplantation

Interventions

etoposide DRUG

Given IV

Also known as: EPEG, VP-16, VP-16-213

Treatment (radiation therapy/chemotherapy, stem cell infusion)

ifosfamide DRUG

Given IV

Also known as: Cyfos, Holoxan, IFF, IFX, IPP

Treatment (radiation therapy/chemotherapy, stem cell infusion)

intensity-modulated radiation therapy RADIATION

Undergo WB-MRI-guided IMRT

Also known as: IMRT

Treatment (radiation therapy/chemotherapy, stem cell infusion)

topotecan hydrochloride DRUG

Given IV

Also known as: hycamptamine, Hycamtin, SKF S-104864-A, TOPO

Treatment (radiation therapy/chemotherapy, stem cell infusion)

busulfan DRUG

Given IV

Also known as: BSF, BU, Misulfan, Mitosan, Myeloleukon

Treatment (radiation therapy/chemotherapy, stem cell infusion)

melphalan DRUG

Given IV

Also known as: Alkeran, CB-3025, L-PAM, L-phenylalanine mustard, L-Sarcolysin

Treatment (radiation therapy/chemotherapy, stem cell infusion)

autologous hematopoietic stem cell transplantation PROCEDURE

Undergo autologous peripheral blood stem cell or bone marrow transplant

Treatment (radiation therapy/chemotherapy, stem cell infusion)

peripheral blood stem cell transplantation PROCEDURE

Undergo autologous peripheral blood stem cell transplant

Also known as: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell

Treatment (radiation therapy/chemotherapy, stem cell infusion)

autologous bone marrow transplantation PROCEDURE

Undergo autologous bone marrow transplant

Also known as: ABMT, bone marrow transplantation, autologous, transplantation, autologous bone marrow

Treatment (radiation therapy/chemotherapy, stem cell infusion)

Eligibility Criteria

• Age: 6 Months - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients with relapsed Ewing's sarcoma or primitive neuroectodermal tumor (PNET) with bony/soft tissue metastasis who achieved at least partial response (PR) to chemotherapy, surgery or radiotherapy
• Newly diagnosed patients with metastatic disease to the bones: patients with metastatic Ewing's or metastatic PNET who achieved at least partial response (PR) to chemotherapy, surgery or radiotherapy are eligible
• Ewing's sarcoma/PNET histology confirmed by Anatomic Pathology Department; histological confirmation of relapse is highly recommended but not mandatory
• Patients must have documented at least partial response (PR) to previous therapy regimens; previous modalities may include surgery, chemotherapy, or radiation therapy; radiation must not include lung fields; only patients in CR or PR at the primary site will be eligible
• Patients must have metastatic/recurrent disease identified by WB-MRI at the time of study entry; intensity-modulated radiation therapy (IMRT) can be delivered per protocol guidelines to at least one but not more than five primary/metastatic sites
• Patients must have Karnofsky performance status \> 60% OR Lansky performance status \> 50% for patients younger than 16 years old
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
• Adequate number of autologous stem cells collected and cryopreserved prior to starting the study treatment
• Creatinine clearance (12 or 24 hour urine collection) or glomerular filtration rate (GFR) \> 60 ml/min/1.73 m\^2
• Ejection fraction \> 50% by echocardiogram or multiple gated acquisition (MUGA)
• Bilirubin \< 2 x upper limit of normal
• Serum glutamic oxalo-acetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) \< 5 x upper limit of normal
• Platelet count \> 50,000/ul
• Absolute granulocyte count \>= 750/ul
• Forced expiratory volume in one second (FEV1) \> 2 liters adults (older than 16 years)

You may not qualify if:

• Patients should not have any uncontrolled illness including ongoing or active infection
• Patients may not be receiving any other investigational agents, concurrent biological agents, or chemotherapy
• Patients must not have received prior chemotherapy or radiation within 2 weeks before study enrollment, and those who have not recovered from the adverse events due to agents administered more than 2 weeks earlier are excluded
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated on this study
• Patients with other active malignancies are ineligible for this study
• Patients with prior treatment with myeloablative therapy are excluded
• Karnofsky performance status \< 60% or Lansky performance status \< 50% for patients younger than 16 years old
• Patients who require irradiation to more than 5 disease sites are excluded
• Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Neuroectodermal Tumors, Primitive, Peripheral

Interventions

Etoposide; Ifosfamide; indolepropanol phosphate; Radiotherapy, Intensity-Modulated; Topotecan; trioctyl phosphine oxide; Busulfan; Melphalan; Peripheral Blood Stem Cell Transplantation; Bone Marrow Transplantation; Transplantation

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Camptothecin; Alkaloids; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Surgical Procedures, Operative; Tissue Transplantation

Study Officials

• Anna Pawlowska

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2013
• First Posted: February 20, 2013
• Study Start: July 1, 2013
• Primary Completion: March 1, 2018
• Last Updated: January 9, 2015

Record last verified: 2015-01

Locations

US (1)