PET Imaging With Tc-94m Sestamibi to Assess Resistance to Chemotherapy

NCT00082368 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 04017704-C-0177
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Cancer

Keywords

Tariquidar; PET; Sestamibi; Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  Sestamibi is a Pgp substrate that may be a surrogate for measuring drug efflux from tumors. Significant increase in the SUV in tumor is +25% over baseline.

  3 days

Secondary Outcomes (1)

• Number of Participants With Adverse Events

  69 months

Study Arms (1)

PET (positron emission imaging) Imaging with Tc-94m Sestamibi

EXPERIMENTAL

PET sestamibi scans followed by tariquidar and repeat imaging

Drug: Tariquidar; Drug: Tc-94m Sestamibi

Interventions

Tariquidar DRUG

3 days after initial PET patients will receive tariquidar and repeat imaging.

PET (positron emission imaging) Imaging with Tc-94m Sestamibi

Tc-94m Sestamibi DRUG

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 will undergo a PET sestamibi scan

PET (positron emission imaging) Imaging with Tc-94m Sestamibi

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (6)

• Advani R, Saba HI, Tallman MS, Rowe JM, Wiernik PH, Ramek J, Dugan K, Lum B, Villena J, Davis E, Paietta E, Litchman M, Sikic BI, Greenberg PL. Treatment of refractory and relapsed acute myelogenous leukemia with combination chemotherapy plus the multidrug resistance modulator PSC 833 (Valspodar). Blood. 1999 Feb 1;93(3):787-95.

  PMID: 9920827 BACKGROUND

• Agrawal M, Abraham J, Balis FM, Edgerly M, Stein WD, Bates S, Fojo T, Chen CC. Increased 99mTc-sestamibi accumulation in normal liver and drug-resistant tumors after the administration of the glycoprotein inhibitor, XR9576. Clin Cancer Res. 2003 Feb;9(2):650-6.

  PMID: 12576431 BACKGROUND

• Bakker M, van der Graaf WT, Piers DA, Franssen EJ, Groen HJ, Smit EF, Kool W, Hollema H, Muller EA, De Vries EG. 99mTc-Sestamibi scanning with SDZ PSC 833 as a functional detection method for resistance modulation in patients with solid tumours. Anticancer Res. 1999 May-Jun;19(3B):2349-53.

  PMID: 10472354 BACKGROUND

• Chen CC, Meadows B, Regis J, Kalafsky G, Fojo T, Carrasquillo JA, Bates SE. Detection of in vivo P-glycoprotein inhibition by PSC 833 using Tc-99m sestamibi. Clin Cancer Res. 1997 Apr;3(4):545-52.

  PMID: 9815718 BACKGROUND

• Bates SE, Bakke S, Kang M, Robey RW, Zhai S, Thambi P, Chen CC, Patil S, Smith T, Steinberg SM, Merino M, Goldspiel B, Meadows B, Stein WD, Choyke P, Balis F, Figg WD, Fojo T. A phase I/II study of infusional vinblastine with the P-glycoprotein antagonist valspodar (PSC 833) in renal cell carcinoma. Clin Cancer Res. 2004 Jul 15;10(14):4724-33. doi: 10.1158/1078-0432.CCR-0829-03.

  PMID: 15269145 BACKGROUND

• 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.

  PMID: 22416063 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Neoplasms

Interventions

tariquidar

Limitations and Caveats

The lack of flexibility around patient chemotherapy schedules made the protocol difficult to conduct. Future studies should make imaging integral to the treatment protocol .

Results Point of Contact

• Title: Dr. Peter Choyke
• Organization: National Cancer Institute

peter_choyke@nih.gov

301-402-8409

Study Officials

• Peter Choyke, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 7, 2006
• First Posted: May 6, 2004
• Study Start: May 16, 2004
• Primary Completion: April 14, 2014
• Study Completion: April 14, 2014
• Last Updated: August 17, 2017
• Results First Posted: May 4, 2015

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)