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MT2004-30: Tomotherapy for Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00623077
Recruitment Status : Terminated (Replaced by another study)
First Posted : February 25, 2008
Last Update Posted : December 5, 2017
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Brief Summary:

RATIONALE: A peripheral blood stem cell transplant or bone marrow transplant using stem cells from the patient may be able to replace immune cells that were destroyed by chemotherapy and image-guided intensity-modulated radiation therapy used to kill tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of bone marrow radiation therapy followed by an autologous stem cell transplant in treating patients with high-risk or relapsed solid tumors.

Condition or disease Intervention/treatment Phase
Brain and Central Nervous System Tumors Kidney Cancer Liver Cancer Retinoblastoma Sarcoma Biological: filgrastim Drug: busulfan Drug: etoposide Drug: ifosfamide Drug: melphalan Drug: thiotepa Procedure: stem cell transplantation Radiation: tomotherapy Radiation: total marrow irradiation Drug: Mesna Radiation: Whole lung radiation Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Dose Escalation of Total Marrow Irradiation Added to an Alkylator-Intense Conditioning Regimen for Patients With High Risk or Relapsed Solid Tumors
Study Start Date : August 2005
Actual Primary Completion Date : July 2012
Actual Study Completion Date : October 2016

Arm Intervention/treatment
Experimental: Total Marrow Irradiation (MTI) with Tomotherapy
TMI given prior to alkylator intensive conditioning regimen (Busulfan 9.6 mg/kg intravenously (IV) (>4 yrs of age) or 13.2 mg/kg IV (< 4 years of age), Melphalan 100 mg/m^2, Thiotepa 500 mg/m^2 for high risk solid tumor patients, Whole lung radiation 1500cGy in 10 fractions by Day 60, stem cell transplantation on day 0. Ifosfamide, etoposide, and mesna are given Days 0-4 followed by filgrastim for 3 doses. Cohorts of patients (n=3) will be treated with increasing doses of TMI (600, 1000, 1200 cGy) directed toward the bones.
Biological: filgrastim

Beginning 24 hours after chemotherapy end: 10 microgram/kg/day subcutaneously (SQ) or intravenously (IV) until absolute neutrophile count (ANC) > 1,000/mm^2.

Starting that day, increase dose to 15 microgram/kg/day SQ or IV given as a single injection for 3 doses.

Other Names:
  • G-CSF
  • Sargramostim

Drug: busulfan
Part of pre-transplant conditioning chemotherapy: Administered as Busulfan 9.6 mg/kg IV (>4 yrs of age) or 13.2 mg/kg IV (< 4 years of age),every 6 hours on Days -8 through -6.
Other Names:
  • Busulfex
  • Myleran

Drug: etoposide
Part of Mobilization chemotherapy and Peripheral blood progenitor cell collections (day -100 to -30): Given as 100 mg/m^2/day intravenous (IV) over 1 hour for 5 days.
Other Names:
  • Eposin
  • VP-16

Drug: ifosfamide
Part of Mobilization chemotherapy and Peripheral blood progenitor cell collections (day -100 to -30): Given as 1.8 g/m^2/day intravenous (IV) over 1 hour on for 5 days.
Other Names:
  • Mitoxana
  • Ifex

Drug: melphalan
Part of pre-transplant conditioning chemotherapy: Administered as 100 mg/m^2 intravenous (IV) over 30 min on Days -5 through -4.
Other Name: Alkeran

Drug: thiotepa
Part of pre-transplant conditioning chemotherapy: Administered as 500 mg/m^2 intravenously (IV) over 2 hrs on Days -3 through -2.

Procedure: stem cell transplantation
Regardless of whether the patient will be receiving peripheral cells or bone marrow, infusion will be intravenous on day 0, immediately after thawing.
Other Name: HPC infusion

Radiation: tomotherapy

We plan to deliver the total marrow irradiation (TMI) to the upper half of the body using Tomotherapy TMI as explained in this protocol. However the lower part of the body will be treated with Anterior/Posterior linac based radiation treatment. Tomotherapy will then be delivered at a dose rate so as to keep the total treatment time to no more than 30 minutes. We anticipate that the dose rate will be around 400 cGy

/minute (instantaneous dose rate).

Radiation: total marrow irradiation
TMI will be delivered to all bony sites as part of the conditioning. Additional "spot" therapy to PET positive lesions, primary disease (if not previously irradiated to maximum tolerated dose), and lungs will be performed on Day +60. Cohorts of 3 patients will be treated at a total dose of 600 cGy, 900 cGy or 1200 cGy on Days -11 through -9.

Drug: Mesna
Part of Mobilization chemotherapy and Peripheral blood progenitor cell collections (day -100 to -30): Given as 1.8 g/m^2/day divided in every 6 hrs dosing for 5 days.
Other Names:
  • Uromitexan®
  • Mesnex

Radiation: Whole lung radiation
At Day 60, patients with prior lung metastasis should receive whole lung irradiation (1500cGy in 10 fractions).

Primary Outcome Measures :
  1. Maximum tolerated dose of tomotherapy up to 12 Gy [ Time Frame: Day 42 ]
    is a state-of-the- art means of delivering highly conformal radiation to tumors of targeted volume with high therapeutic gain. Tomotherapy offers unique advantages over total body irridiation and is expected to improve clinical outcome. The MTD is defined as the highest dose studied for which the incidence of dose limiting toxicity is less than 33%.

Secondary Outcome Measures :
  1. Percent of patients who had PET scans and "spot radiation" to PET-positive lesions after transplantation [ Time Frame: Day 60 Post Transplant ]
    PET-CT scan is done prior to and after transplant. Radiation is given before and after transplant.

  2. Change in bone mineral density [ Time Frame: Baseline, 6 and 12 Months Post Transplantation ]
    the change in bone density and turnover in patients exposed to alkylator intensive conditioning regimen followed by tomographic total marrow irradiation (TMI).

  3. Rate of Treatment Related Mortality in Non-TMI Treated Patients [ Time Frame: Day 100 Post Transplant ]
    Determined in patients who were not treated with total marrow irradiation; all deaths without previous relapse or progression are usually considered as related to transplantation.

  4. Rate of Primary Neutrophil Engraftment [ Time Frame: Day 42 ]
    Neutrophil engraftment is defined as the first day of three consecutive days where the neutrophil count (absolute neutrophil count) is 500 cells/mm3 (0.5 x 109/L) or greater.

  5. Overall Survival [ Time Frame: From date of enrollment to date of death or censored at the date of last documented contact ]
    Determined in patients not receiving total marrow irradiation. The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. Also called survival rate.

  6. Disease-Free Survival [ Time Frame: 1 Year ]
    In patients not receiving total marrow irradiation, the length of time after treatment ends that a patient survives without any signs or symptoms of that cancer or any other type of cancer. In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works.

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis Patients must have had histologic verification of malignancy at original diagnosis. Diseases included are:

    • Ewing's Family Tumors (ES/PNET/DSRCT): metastatic at the time of diagnosis and/or relapsed after therapy
    • Renal tumors: relapsed (all histology-Wilm's tumor) or at diagnosis (clear cell sarcoma and Rhabdoid tumor),
    • Hepatoblastoma: metastatic at the time of diagnosis and/or relapsed after therapy
    • Rhabdomyosarcoma: metastatic at the time of diagnosis and/or relapsed after therapy
    • Soft tissue sarcomas: chemotherapy responsive metastatic disease or chemotherapy responsive relapsed disease
    • Primary Malignant Brain Neoplasms at diagnosis and/or relapse
    • Retinoblastoma: disseminated at diagnosis and/or relapsed
    • Other High Risk Metastatic or Relapsed Solid Tumors: To be approved by two or more physicians on the study committee
  • Disease Status: Patients must have either: 1) no evidence of disease or 2) stable, non-progressive disease (defined as non-progressive abnormalities on physical exam or computated tomography (CT) and/or magnetic resonance imaging [MRI]) within 4 weeks of study entry.
  • Age: Patients must be 0-70 years of age at the time of study entry.
  • Performance Level: Karnofsky > or = 50% for patients > 10 years of age and Lansky > or = 50% for patients < or = 10 years of age. Note: Neurologic deficits in patients with central nervous system (CNS) tumors must be stable for a minimum of 1 week prior to study entry.
  • Organ Function:

    • Hematologic: prior to receiving total marrow irradiation (TMI) patients should have a hemoglobin of >10 gm/dl and a platelet count > 20,000/μl. Patients may receive transfusions as necessary.
    • Renal: glomerular flow rate (GFR) ≥ 50 ml/min/1.73m^2 or serum creatinine ≤ 2.5 x upper limit of normal (ULN) for age
    • Hepatic: aspartate aminotransferase/alanine aminotransferase (AST or ALT) ≤ 5 x ULN and bilirubin ≤ 5 x ULN
    • Cardiac: ejection fraction > 45% or no clinical evidence of heart failure
    • Pulmonary: oxygen saturation > 92% at rest (on room air)

Exclusion Criteria:

  • Disease Status: patients with progressive, non-therapy responsive disease will not be eligible.
  • Infection: patients who have active, uncontrolled infections or those who are HIV+.
  • Pregnancy or Breast-Feeding: pregnant or breast-feeding women will not be entered on this study.
  • Prior Radiation Therapy: patients must be eligible to receive TMI via tomographic radiation therapy (as determined by radiation oncology staff). If not eligible (due to extensive prior radiation or other circumstances), patients can be treated on study but will not receive radiation and will be analyzed on a separate arm.

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 identifier (NCT number): NCT00623077

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United States, Minnesota
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
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Principal Investigator: Michael R. Verneris, MD Masonic Cancer Center, University of Minnesota
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Responsible Party: Masonic Cancer Center, University of Minnesota Identifier: NCT00623077    
Other Study ID Numbers: 2005LS023
UMN-MT2004-30 ( Other Identifier: Blood and Marrow Transplantation Program )
0504M69306 ( Other Identifier: IRB, University of Minnesota )
First Posted: February 25, 2008    Key Record Dates
Last Update Posted: December 5, 2017
Last Verified: December 2017
Keywords provided by Masonic Cancer Center, University of Minnesota:
metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor
recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor
childhood hepatoblastoma
recurrent childhood liver cancer
stage IV childhood liver cancer
adult primary liver cancer
previously treated childhood rhabdomyosarcoma
recurrent childhood rhabdomyosarcoma
previously untreated childhood rhabdomyosarcoma
metastatic childhood soft tissue sarcoma
recurrent childhood soft tissue sarcoma
recurrent adult soft tissue sarcoma
stage IV adult soft tissue sarcoma
recurrent Wilms tumor and other childhood kidney tumors
stage IV Wilms tumor
stage V Wilms tumor
rhabdoid tumor of the kidney
stage IV renal cell cancer
childhood mixed glioma
recurrent childhood cerebellar astrocytoma
recurrent childhood cerebral astrocytoma
recurrent childhood ependymoma
recurrent childhood medulloblastoma
recurrent childhood pineoblastoma
recurrent childhood supratentorial primitive neuroectodermal tumor
recurrent childhood visual pathway glioma
untreated childhood brain stem glioma
untreated childhood cerebellar astrocytoma
childhood infratentorial ependymoma
childhood supratentorial ependymoma
Additional relevant MeSH terms:
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Liver Neoplasms
Kidney Neoplasms
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Neoplasms, Glandular and Epithelial
Nervous System Diseases
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Retinal Neoplasms
Eye Neoplasms
Eye Diseases, Hereditary
Eye Diseases
Retinal Diseases