Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Combination Targeted Radiotherapy in Neuroendocrine 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.
ClinicalTrials.gov Identifier: NCT01099228
Recruitment Status : Completed
First Posted : April 6, 2010
Last Update Posted : July 21, 2016
Sponsor:
Collaborator:
VA Office of Research and Development
Information provided by (Responsible Party):
David Bushnell, University of Iowa

Brief Summary:
The primary aim of this project is to determine, what fraction of individuals with neuroendocrine tumors would show substantially improved tumor dosimetry with combined agent therapy compared to "best" single agent therapy and determine the magnitude of the potential tumor radiation dose increase.

Condition or disease Intervention/treatment Phase
Neuroendocrine Tumors Other: 131-I MIBG and 111-In pentetreotide Other: 131-I MIBG and In-111 DOTATATE Not Applicable

Detailed Description:

RESEARCH PLAN / BACKGROUND AND SIGNIFICANCE:

Tumors originating from the neuroendocrine system, although relatively rare, may be life threatening. In cases where the disease has metastasized, the 5 year survival is very poor. 131I meta-iodobenzylguanidine (MIBG)and 90Y DOTA-D-Phe1-Tyr3-Octreotide (DOTATOC) are two radiopharmaceuticals that have shown promise as therapeutic agents in patients with metastatic neuroendocrine tumors. However, delivering sufficient radiation dose to the tumor to obtain objective anti-tumor responses or cure with these radiopharmaceuticals is challenging because of the allowable dose limits imposed by radiation damage to normal tissues. Organ biodistribution and kinetics of 90Y DOTATOC and 131I MIBG are substantially different, which leads to different critical organs for these agents, the kidney for Y90Y DOTATOC and the red marrow for 131I MIBG. We propose to investigate a mechanism to increase the radiation dose delivered to tumors without exceeding "critical" radiation dose to normal organs by combining 90Y DOTATOC and 131I MIBG.

AIMS / OBJECTIVES:

The primary aim of this project is to determine, what fraction of individuals with neuroendocrine tumors would show substantially improved tumor dosimetry with combined agent therapy compared to "best" single agent therapy and determine the magnitude of the potential tumor radiation dose increase.

METHODS:

To achieve this, we plan to perform serial scintigraphic imaging procedures to measure patient specific bone marrow, kidney, and tumor biodistribution and kinetics for 111In Pentetreotide and 131I-MIBG in adults and children with neuroendocrine tumors. Then, using the program we have already developed, we will input the individual dosimetry measures for bone marrow, kidney and tumor to determine the optimal amounts of administered radioactivity for the combination of 131I MIBG plus 90Y DOTATOC or 131I MIBG alone.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Combination Targeted Radiotherapy in Neuroendocrine Tumors
Study Start Date : September 2006
Actual Primary Completion Date : April 2008
Actual Study Completion Date : July 2015


Arm Intervention/treatment
Active Comparator: 131-I MIBG and 111I-n pentetreotide
131-I MIBG and 111I-n pentetreotide
Other: 131-I MIBG and 111-In pentetreotide
Subjects will receive 131I MIBG and 111In pentetreotide(surrogate for Y90-DOTATOC)

Active Comparator: 131-I MIBG and In-111 DOTATATE
131-I MIBG and In-111 DOTATATE
Other: 131-I MIBG and In-111 DOTATATE
131I MIBG and In-111 DOTATATE (surrogate for 177Lu DOTATATE)




Primary Outcome Measures :
  1. Dosimetry Results [ Time Frame: 1 week after scan ]
    Determine the patient specific bone marrow, kidney and tumor dosimetry results for each subject from the 2 groups will be used to calculate the optimal combination of administered activities for 131I-MIBG plus 90Y-DOTATOC (group 1) 131I-MIBG plus 177Lu-DOTATATE (group 2) and the resultant dose delivery to tumor from each combination


Secondary Outcome Measures :
  1. Maximum Radiation Dose [ Time Frame: 3 months ]
    Calculate the optimal amount for either agent when administered individually along with corresponding tumor radiation dose to determine the amount of each product will give maximum tumor kill and not damage other vunerable organs..



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects with biopsy-proven metastatic (soft tissue) neuroendocrine tumors.
  • Subjects with a Southwest Oncology Group (SWOG) performance score of 0-2 and an expected median survival of at least 6 months.
  • The subject is able and willing to comply with study procedures and a signed and dated informed consent is obtained.
  • Subjects must be >18 years of age

Exclusion Criteria:

  • Subjects who use medications that are known to interfere with MIBG uptake and is unable to discontinue for medical reasons.
  • Prior chemotherapy, radiotherapy or any investigational drugs within 60 days prior admission into this study. Patients must have recovered from all therapy-related toxicities
  • Renal insufficiency with a serum creatinine 2 X ULN
  • Subjects unable to lie still for the imaging studies.
  • Subjects who because of their weight and body distribution do not fit into the imaging machine.
  • Subjects receiving Sandostatin LAR < 21 days prior to dosing or Sandostatin Immediate Release (IR) < 24 hours prior to dosing.
  • Female patients who are pregnant or breast feeding. Women of childbearing potential must have a negative serum/urine pregnancy test within 48 hours prior to administration of study treatment.

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 ClinicalTrials.gov identifier (NCT number): NCT01099228


Locations
Layout table for location information
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
Department of Veteran Affairs Medical Center
Iowa City, Iowa, United States, 52246
Sponsors and Collaborators
David Bushnell
VA Office of Research and Development
Investigators
Layout table for investigator information
Principal Investigator: David Bushnell, M.D. University of Iowa; Veteran Affairs

Layout table for additonal information
Responsible Party: David Bushnell, Professor, Radiology, University of Iowa
ClinicalTrials.gov Identifier: NCT01099228     History of Changes
Other Study ID Numbers: 200602763
First Posted: April 6, 2010    Key Record Dates
Last Update Posted: July 21, 2016
Last Verified: July 2016

Keywords provided by David Bushnell, University of Iowa:
Neuroendocrine Tumor
Imaging

Additional relevant MeSH terms:
Layout table for MeSH terms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
3-Iodobenzylguanidine
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Radiopharmaceuticals