Clinical trial NCT00082368: PET Imaging With Tc-94m Sestamibi to Assess Resistance to Chemotherapy
Official title: A Pilot Study of Tc-94m Sestamibi PET MDR Imaging
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cancer
Keywords: Tariquidar
PET
Sestamibi
Cancer
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2004-05-06
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: Background:

* Tc-94m sestamibi is a radioactive imaging drug approved by the Food and Drug Administration to help photograph and study bodily functions.
* Tc-94m sestamibi accumulates in tumor cells and is eliminated from them in much the same way that some chemotherapy drugs are eliminated from cancer cells in patients with drug resistance.
* P-glycoprotein is a protein found on the surface of some cancer cells. The protein causes the cells to pump out, or reject, some types of chemotherapy drugs. P-glycoprotein also makes the cells reject sestamibi.
* Some drugs, including a drug called tariquidar, may block the pumping action of P-glycoprotein, giving the chemotherapy more time to work. Tariquidar can also help sestamibi stay in the cells longer.

Objectives:

-To evaluate the use of sestamibi for determining if chemotherapy is being rejected and if enough of the blocking drugs are present to stop the rejection.

Eligibility:

-Patients18 years of age and older with a tumor 2 cm or larger who are enrolled in or are eligible for enrollment in an active National Cancer Institute treatment protocol.

Design:

* Patients have two scans, one before receiving any drugs and a second 1-2 hours after receiving tariquidar. The second scan is done 72 or more hours after the first. For both scans, Tc-94m sestamibi is injected into a vein and a series of pictures are taken with an imaging camera called a PET (positron emission tomography) scanner. The pictures show where the sestamibi distributes in the body and monitors the effects of tariquidar on drug resistance. Blood samples are collected during the scan to examine the effect of tariquidar on P-glycoprotein in normal cells.
* Some patients may be asked to undergo a tumor biopsy to test for the presence of the P-glycoprotein on their cancer cells. This will be requested only in patients whose tumor is easily accessible and in whom a biopsy can be done with minimal risk.

Detailed description: Background:

* A pilot study of PET imaging with Tc-94m sestamibi to assess activity of the multidrug transporter, MDR-1 (Multi Drug Resistance Protein 1)/P-glycoprotein, an ATP (adenosine 5'-triphosphate)-binding cassette protein that transports drug out of the cell, thereby reducing intracellular drug accumulation.
* Tariquidar is a safe, nontoxic antagonist of P-glycoprotein. Previous studies demonstrated that tariquidar increased retention of the radioimaging agent, Tc99 sestamibi in normal liver and in a subset of tumors. These studies were limited by the semiquantitative nature of total body imaging by conventional radionuclide scintigraphy
* In collaboration with the Clinical Center Nuclear Medicine Department, a PET imaging agent has been developed, Tc-94m sestamibi, and the FDA (Food and Drug Administration) has granted approval for its use in humans.

Objectives:

-To evaluate the feasibility of Tc-94m sestamibi as a PET imaging agent, which should allow greater resolution and quantitation and thereby make possible direct quantitative comparisons of tumor uptake before and after treatment with a P-glycoprotein antagonist.

Eligibility:

* Patients over 18 years of age, who are eligible for, or have completed enrollment in an active NCI (National Cancer Institute) protocol for treatment of cancer.
* Negative pregnancy test within 24 hrs of Tc-94m injection.
* An index lesion greater than 2cm will be required to optimize the PET images.
* Prior treatment with a P-glycoprotein antagonist is allowed.

Design:

* Designed as a feasibility study. Patients meeting the eligibility criteria and signing informed consent will undergo a PET sestamibi imaging scan in the Department of Nuclear Medicine. Seventy-two hours later, a dose of tariquidar will be administered before a repeat imaging study.
* Blood will be obtained for analysis of the pharmacokinetics of Tc-94m sestamibi, and for isolation of peripheral blood mononuclear cells to assay P-glycoprotein inhibition in circulating CD56+ cells. These assessments are needed to confirm the impact of tariquidar on P-glycoprotein in normal cells - for example, those involved in drug excretion and in circulating mononuclear cells. These results will then be used to inform the findings in the PET imaging study.
* Fifteen patients will be enrolled and pairwise comparisons will be made between the sestamibi residence times in tumor, normal liver, kidney, and heart. All comparisons are noted to be exploratory.

Eligibility criteria: * INCLUSION CRITERIA:

Patients must be eligible for enrollment in an active NCI (National Cancer Institute) protocol for treatment of cancer.

Patients greater than or equal to 18 years old.

Performance Status ECOG (Eastern Cooperative Oncology Group) 0 - 2.

Patients must be able to give informed consent.

Women of childbearing potential must have a negative pregnancy test within 24 hrs of Tc-94m injection.

Patients who have previously received tariquidar will be eligible, since no study has systematically shown loss of MDR-1 (Multi Drug Resistance Protein 1)/Pgp expression in tumors following exposure to both tariquidar and an anticancer agent.

An index lesion greater than 1.5 cm will be required to optimize the PET (positron emission imaging) images.

EXCLUSION CRITERIA:

Patients who are pregnant or breast-feeding will not be enrolled in order to prevent radiation exposure in the developing fetus or infant.

Patients weighing greater than 136 kg (the weight limit for the scanner table).

Patients having only tumor sizes less than 1.5 cm will be excluded.

HIV (human immunodeficiency virus) positive patients will be excluded to prevent potential drug interactions between tariquidar and antiretroviral agents.

Primary outcomes:
measure: Percent Change in Tc-94m Sestamibi Body Weight Standardized Uptake Value (SUV) Maximum in Tumor Tissue Before and After Administration of Tariquidar, a P-glycoprotein Antagonist.
timeFrame: 3 days
Secondary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: 69 months
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center, 9000 Rockville Pike
state: Maryland
Study officials:
affiliation: National Cancer Institute (NCI)
name: Peter Choyke, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Kelly RJ, Robey RW, Chen CC, Draper D, Luchenko V, Barnett D, Oldham RK, Caluag Z, Frye AR, Steinberg SM, Fojo T, Bates SE. A pharmacodynamic study of the P-glycoprotein antagonist CBT-1(R) in combination with paclitaxel in solid tumors. Oncologist. 2012;17(4):512. doi: 10.1634/theoncologist.2012-0080. Epub 2012 Mar 13.