MT2004-30: Tomotherapy for Solid Tumors

NCT00623077 | Terminated Phase 1 DMC

• 3 other identifiers: 2005LS023UMN-MT2004-300504M69306
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of tomotherapy up to 12 Gy

  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%.

  Day 42

Secondary Outcomes (6)

• Percent of patients who had PET scans and "spot radiation" to PET-positive lesions after transplantation

  Day 60 Post Transplant

• Change in bone mineral density

  Baseline, 6 and 12 Months Post Transplantation

• Rate of Treatment Related Mortality in Non-TMI Treated Patients

  Day 100 Post Transplant

• Rate of Primary Neutrophil Engraftment

  Day 42

• Overall Survival

  From date of enrollment to date of death or censored at the date of last documented contact

Study Arms (1)

Total Marrow Irradiation (MTI) with Tomotherapy

EXPERIMENTAL

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; 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

Interventions

filgrastim BIOLOGICAL

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.

Also known as: G-CSF, Sargramostim

Total Marrow Irradiation (MTI) with Tomotherapy

busulfan DRUG

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.

Also known as: Busulfex, Myleran

Total Marrow Irradiation (MTI) with Tomotherapy

etoposide DRUG

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.

Also known as: Eposin, VP-16

Total Marrow Irradiation (MTI) with Tomotherapy

ifosfamide DRUG

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.

Also known as: Mitoxana, Ifex

Total Marrow Irradiation (MTI) with Tomotherapy

melphalan DRUG

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

Also known as: Alkeran

Total Marrow Irradiation (MTI) with Tomotherapy

thiotepa DRUG

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

Total Marrow Irradiation (MTI) with Tomotherapy

stem cell transplantation PROCEDURE

Regardless of whether the patient will be receiving peripheral cells or bone marrow, infusion will be intravenous on day 0, immediately after thawing.

Also known as: HPC infusion

Total Marrow Irradiation (MTI) with Tomotherapy

tomotherapy RADIATION

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).

Total Marrow Irradiation (MTI) with Tomotherapy

total marrow irradiation RADIATION

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.

Total Marrow Irradiation (MTI) with Tomotherapy

Mesna DRUG

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.

Also known as: Uromitexan®, Mesnex

Total Marrow Irradiation (MTI) with Tomotherapy

Whole lung radiation RADIATION

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

Total Marrow Irradiation (MTI) with Tomotherapy

Eligibility Criteria

• Age: Up to 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Kidney Neoplasms; Liver Neoplasms; Retinoblastoma; Sarcoma; Neuroectodermal Tumors, Primitive, Peripheral; Hepatoblastoma; Carcinoma, Hepatocellular; Wilms Tumor; Carcinoma, Renal Cell; Astrocytoma; Familial ependymoma; Medulloblastoma; Optic Nerve Glioma; Rhabdoid Tumor

Interventions

Filgrastim; Granulocyte Colony-Stimulating Factor; sargramostim; Busulfan; Etoposide; Ifosfamide; Melphalan; Thiotepa; Stem Cell Transplantation; Radiotherapy, Intensity-Modulated; Mesna

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Retinal Neoplasms; Eye Neoplasms; Eye Diseases, Hereditary; Eye Diseases; Retinal Diseases; Neoplasms, Connective and Soft Tissue; Neuroectodermal Tumors, Primitive; Neoplasms, Complex and Mixed; Adenocarcinoma; Carcinoma; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Glioma; Optic Nerve Neoplasms; Cranial Nerve Neoplasms; Peripheral Nervous System Neoplasms; Cranial Nerve Diseases; Optic Nerve Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Triethylenephosphoramide; Aziridines; Azirines; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Sulfhydryl Compounds

Study Officials

• Michael R. Verneris, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2008
• First Posted: February 25, 2008
• Study Start: August 1, 2005
• Primary Completion: July 1, 2012
• Study Completion: October 1, 2016
• Last Updated: December 5, 2017

Record last verified: 2017-12

Locations

US (1)