Clinical trial NCT00623077: MT2004-30: Tomotherapy for Solid Tumors
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Brain and Central Nervous System Tumors
Kidney Cancer
Liver Cancer
Retinoblastoma
Sarcoma
Keywords: 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
childhood high-grade cerebellar astrocytoma
childhood high-grade cerebral astrocytoma
childhood low-grade cerebellar astrocytoma
childhood low-grade cerebral astrocytoma
newly diagnosed childhood ependymoma
childhood atypical teratoid/rhabdoid tumor
recurrent retinoblastoma
extraocular retinoblastoma
intraocular retinoblastoma
childhood renal cell carcinoma
clear cell renal cell carcinoma
recurrent renal cell cancer
recurrent childhood visual pathway and hypothalamic glioma
unspecified adult solid tumor, protocol specific
unspecified childhood solid tumor, protocol specific
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2008-02-25
Enrollment: 23
Sex: ALL
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: OBJECTIVES:

Primary

* To determine the maximum tolerated dose of tomographic total marrow irradiation (TMI) when given prior to an alkylator-intensive conditioning regimen in patients with high-risk or relapsed solid tumors.

Secondary

* To determine the feasibility of performing positron emission tomography (PET) scans and spot radiation to PET-positive lesions after transplantation.
* To determine the change in bone mineral density and turnover in patients treated with an alkylator-intensive conditioning regimen and TMI.

OUTLINE:

* Mobilization chemotherapy and peripheral blood progenitor cell (PBPC) collection: Patients receive ifosfamide intravenously (IV) and etoposide IV on days -100 through -30.

Beginning 24 hours after completion of chemotherapy, patients receive filgrastim (G-CSF) subcutaneously (SC) or IV until blood counts recover. Patients then receive an increased dose of G-CSF SC or IV once daily for 3 consecutive days. Beginning on day -97, patients undergo up to 4 collections of PBPCs. Patients who do not yield an adequate number of cells undergo bone marrow harvest.

* Bone marrow harvest: Patients undergo bone marrow aspirate and biopsy 2 weeks after the last dose of G-CSF. If the aspirate or biopsy is morphologically free of tumor cells and demonstrates \> 20% cellularity, then patients receive sargramostim (GM-CSF) daily for 5 days followed by bone marrow harvest.
* Total marrow irradiation (TMI) with tomotherapy: Patients undergo escalating doses of TMI\* to all bony sites using helical tomotherapy image-guided intensity-modulated radiotherapy on days -11 to -9.

NOTE: \*Patients with primary CNS tumors do not receive TMI but are eligible to receive chemotherapy and hematopoietic progenitor cell rescue in accordance with the protocol.

* Conditioning regimen: Patients receive busulfan IV over 2 hours four times daily on days -8 to -6, high-dose melphalan IV over 30 minutes on days -5 to -4, and thiotepa IV over 2 hours on days -3 to -2.
* Autologous CD34+ hematopoietic progenitor cell transplantation: Patients undergo reinfusion of autologous G-CSF-mobilized peripheral blood or bone marrow progenitor cells on day 0. Patients also receive G-CSF support beginning on day 0 and continuing until blood counts recover for 2 consecutive days.
* Post-transplantation radiotherapy: Patients may receive additional radiotherapy to areas of known metastatic disease, PET-positive lesions, primary disease (if not previously irradiated to maximum tolerated dose), and lungs beginning on day 60 post transplantation. Patients with prior lung metastasis may receive up to 10 fractions of whole-lung irradiation.

Patients may also receive additional radiotherapy to primary disease if maximum tolerated dose has not yet been reached.

Patients undergo bone mineral density studies at baseline and at days 60, 120, and 180 post transplantation. Patients also undergo blood sample collection periodically during study for pharmacokinetic analysis of busulfan.

Patients undergo PET scans at baseline and on day 60.

After completion of study therapy, patients are followed at days 180 and 365 and then periodically thereafter.

Eligibility criteria: 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.

Primary outcomes:
measure: Maximum tolerated dose of tomotherapy up to 12 Gy
timeFrame: Day 42
Secondary outcomes:
measure: Percent of patients who had PET scans and "spot radiation" to PET-positive lesions after transplantation
timeFrame: Day 60 Post Transplant
measure: Change in bone mineral density
timeFrame: Baseline, 6 and 12 Months Post Transplantation
measure: Rate of Treatment Related Mortality in Non-TMI Treated Patients
timeFrame: Day 100 Post Transplant
measure: Rate of Primary Neutrophil Engraftment
timeFrame: Day 42
measure: Overall Survival
timeFrame: From date of enrollment to date of death or censored at the date of last documented contact
measure: Disease-Free Survival
timeFrame: 1 Year
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center at University of Minnesota
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Michael R. Verneris, MD
role: PRINCIPAL_INVESTIGATOR
References: