Clinical trial NCT01099228: Combination Targeted Radiotherapy in Neuroendocrine Tumors
Official title: Combination Targeted Radiotherapy in Neuroendocrine Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Neuroendocrine Tumors
Keywords: Neuroendocrine Tumor
Imaging
Lead sponsor: University of Iowa
Sponsor class: OTHER
Collaborators: name: VA Office of Research and Development
First posted: 2010-04-06
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Dosimetry Results
timeFrame: 1 week after scan
Secondary outcomes:
measure: Maximum Radiation Dose
timeFrame: 3 months
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Iowa City
country: United States
facility: Department of Veteran Affairs Medical Center
state: Iowa
Study officials:
affiliation: University of Iowa; Veteran Affairs
name: David Bushnell, M.D.
role: PRINCIPAL_INVESTIGATOR
References: