NCT00623077

MT2004-30: Tomotherapy for Solid Tumors

Dose Escalation of Total Marrow Irradiation Added to an Alkylator-Intense Conditioning Regimen for Patients With High Risk or Relapsed Solid Tumors

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 23 (actual)
• Sponsor: Masonic Cancer Center, University of Minnesota · Academic / Other
• Sex: All
• Age: 70 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Brain and Central Nervous System Tumors
• Kidney Cancer
• Liver Cancer
• Retinoblastoma
• Sarcoma

Interventions

Type	Name	Description
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.
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.
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.
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.
DRUG	melphalan	Part of pre-transplant conditioning chemotherapy: Administered as 100 mg/m\^2 intravenous (IV) over 30 min on Days -5 through -4.
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.
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.
RADIATION	Whole lung radiation	At Day 60, patients with prior lung metastasis should receive whole lung irradiation (1500cGy in 10 fractions).

Timeline

• Start date: 2005-08-01
• Primary completion: 2012-07-01
• Completion: 2016-10-01
• First posted: 2008-02-25
• Last updated: 2017-12-05

Locations

1 site across 1 country: United States