Gallium 68 Pentixafor in Patients With Neuroendocrine Tumors

• ClinicalTrials.gov Identifier: NCT03335670
• Recruitment Status: Recruiting
• First Posted: November 8, 2017
• Last Update Posted: April 4, 2019
• Sponsor: Yusuf Menda
• Collaborators: National Cancer Institute (NCI); National Institutes of Health (NIH); Holden Comprehensive Cancer Center
• Information provided by (Responsible Party): Yusuf Menda, University of Iowa

Study Description

Brief Summary:

This study will evaluate how Gallium-68 Pentixafor is distributed in neuroendocrine tumor patients and if that distribution is consistent through repeated scans. This is an RDRC study - as such, the images obtained for this study cannot be used clinically or shared with treating oncologists.

Condition or disease	Intervention/treatment	Phase
Neuroendocrine Tumors	Drug: [68Ga]Pentixafor	Early Phase 1

Detailed Description:

High grade neuroendocrine tumors often do not express somatostatin (sstr) receptors but often express the CXCR4 receptor. The CXCR4 receptor is a marker of poorly differentiated cells. Pentixafor is a peptide that targets these CXCR4 receptors. By combining it with gallium-68, a radionuclide, pentixafor can then be evaluated as an imaging agent to detect high-grade neuroendocrine tumors.

[68Ga]Pentixafor is a radio-labelled imaging agent used for positron emission tomography (PET). The dose is small, known as a tracer dose. It is designed to capture information about the body and how the body is working without interfering or causing an effect.

The goal of this study is to evaluate how the [68Ga]Pentixafor is distributed through the body after injection and how it is taken up by the organs of the body. The study will also examine if the imaging is reproducible to determine if the PET images show the same uptake of the study drug across different scans.

This study is an RDRC study - the equivalent to a phase 0 study. The [68Ga]Pentixafor has not been shown to target tumors; specificity and sensitivity have not been established. For this reason, images obtained for this study cannot be used clinically or shared with treating oncologists.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Biodistribution of Ga-68 Pentixafor in Patients With Neuroendocrine Tumors
• Actual Study Start Date: November 3, 2017
• Estimated Primary Completion Date: October 1, 2019
• Estimated Study Completion Date: December 31, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: [68Ga]Pentixafor PET scan; 4 mCi (range 3-5 mCi) of [68Ga]Pentixafor is administered intravenously over 1 minute using an infusion pump. PET imaging is performed from time of infusion for about 90 minutes. Approximately 12 blood samples (~ 1 tsp) will be taken for pharmacokinetic analysis.	Drug: [68Ga]Pentixafor; 68Ga Pentixafor is a radiolabeled cyclic pentapeptide with high affinity for CXCR4 receptor; Other Name: (68Ga)pentixafor

Outcome Measures

Primary Outcome Measures :

1. Determine biodistribution (pharmacokinetic parameters) of [68Ga]Pentixafor in patients with neuroendocrine tumors (NETs) [ Time Frame: Within 1 month of [68Ga]Pentixafor scan ]
   Biodistribution will be assessed through the radiotracer parameters standardized uptake value (SUV) and K-influx obtained from PET scan and blood samples.These values provide a pharmacokinetic profile of the investigational drug's biodistribution in the body.
2. Determine the repeatability of [68Ga]Pentixafor uptake in known neuroendocrine tumor lesions [ Time Frame: Within 1 month of the second [68Ga]Pentixafor scan ]
   Determine the difference, in any, of the biodistribution values between scans 1 and 2, for subjects who undergo 2 [68Ga]Pentixafor scans.

Secondary Outcome Measures :

1. Compare standardized uptake values of [68Ga]Pentixafor and [68Ga]DOTATATE in known neuroendocrine tumor lesions [ Time Frame: Within 6 months of [68Ga]Pentixafor scan ]
   The standardized uptake value (SUV) of known neuroendocrine tumors for the investigational agent [68Ga]Pentixafor will be compared to the SUV for [68Ga]DOTATATE (NetSpot).
2. Correlate the uptake of [68Ga]Pentixafor and [68Ga]DOTATATE (NetSpot) in known neuroendocrine tumor lesions with expression of receptors (CXCR4 and SSTR2) in biopsy tissue samples. [ Time Frame: Within 6 months of [68Ga]Pentixafor scan ]
   The standardized uptake value (SUV) of the gallium PET tracers ( [68Ga]Pentixafor and/or [68Ga]DOTATATE) will be compared to the receptor expression score (H-score)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Age ≥ 18 years
2. Histological diagnosis of neuroendocrine tumor (NET).
3. Had a prior 68Ga DOTATATE PET/CT scan (NetSpot) and a CT or MRI with or without contrast performed within 3 months before signing the consent, without interval treatment other than a somatostatin analog.
4. CT or MRI must demonstrate at least one lesion (primary or metastatic) present 1.5 cm or larger in any dimension on cross-sectional imaging (CT or MRI) obtained within 3 months of study enrollment.
5. Results of CXCR4 immunohistochemistry or slides from biopsy of primary tumor or metastatic lesions available for study analysis.
6. Participation in the Iowa Neuroendocrine Tumor Registry.

Exclusion Criteria:

1. Uncontrolled intercurrent illness including, but not limited to ongoing or active infection requiring hospitalization, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
2. Physical limitation that would limit compliance with the study requirements
3. Pregnant or lactating women. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A negative pregnancy test will be required for all female subjects with child bearing potential.
4. Planned administration of any NET therapy between scan 1 and 2, except for Somatostatin analog.

Contacts and Locations

Contacts

Contact: Veronica Howsare, AA, MA; (319) 384-6469; veronica-howsare@uiowa.edu

Contact: Kristin Gaimari-Varner, RN, BSN; (319) 384-5489; kristin-gaimari-varner@uiowa.edu

Locations

United States, Iowa

Holden Comprehensive Cancer Center; Recruiting

Iowa City, Iowa, United States, 52242

Contact: Veronica Howsare, AA, MA veronica-howsare@uiowa.edu

Contact: Kristin Gaimari-Varner, RN, BSN (319) 384-5489 kristin-gaimari-varner@uiowa.edu

Principal Investigator: Yusuf Menda, MD

Principal Investigator: M. S. O'Dorisio, MD, PhD

Sub-Investigator: Gideon Zamba, PhD

Sub-Investigator: Andrew Bellizzi, MD

Sub-Investigator: Daniel Berg, MD

Sub-Investigator: David Bushnell, MD

Sub-Investigator: Chandrikha Chandrasekharan, MD

Sub-Investigator: David Dick, PhD

Sub-Investigator: Joseph Dillon, MD

Sub-Investigator: Lisa Dunnwald, MPH

Sub-Investigator: Kristin Gaimari-Varner, RN, BSN

Sub-Investigator: Silvia Ghobrial, MD

Sub-Investigator: Michael M. Graham, MD, PhD

Sub-Investigator: Veronica Howsare, AA, MA

Sub-Investigator: Shannon Lehman, BA

Sub-Investigator: Thomas O'Dorisio, MD

Sub-Investigator: Janet Pollard, MD

Sub-Investigator: Laura Ponto, PhD

Sub-Investigator: Mary Schall, RN, BSN

Sub-Investigator: John Sunderland, PhD

Sponsors and Collaborators

Yusuf Menda

National Cancer Institute (NCI)

National Institutes of Health (NIH)

Holden Comprehensive Cancer Center

Investigators

• Principal Investigator: Yusuf Menda, MD; University of Iowa
• Principal Investigator: M. Sue O'Dorisio, MD, PhD; University of Iowa

More Information

Publications:

Lapa C, Lückerath K, Kleinlein I, Monoranu CM, Linsenmann T, Kessler AF, Rudelius M, Kropf S, Buck AK, Ernestus RI, Wester HJ, Löhr M, Herrmann K. (68)Ga-Pentixafor-PET/CT for Imaging of Chemokine Receptor 4 Expression in Glioblastoma. Theranostics. 2016 Jan 25;6(3):428-34. doi: 10.7150/thno.13986. eCollection 2016.

Bluemel C, Hahner S, Heinze B, Fassnacht M, Kroiss M, Bley TA, Wester HJ, Kropf S, Lapa C, Schirbel A, Buck AK, Herrmann K. Investigating the Chemokine Receptor 4 as Potential Theranostic Target in Adrenocortical Cancer Patients. Clin Nucl Med. 2017 Jan;42(1):e29-e34.

Herhaus P, Habringer S, Philipp-Abbrederis K, Vag T, Gerngross C, Schottelius M, Slotta-Huspenina J, Steiger K, Altmann T, Weißer T, Steidle S, Schick M, Jacobs L, Slawska J, Müller-Thomas C, Verbeek M, Subklewe M, Peschel C, Wester HJ, Schwaiger M, Götze K, Keller U. Targeted positron emission tomography imaging of CXCR4 expression in patients with acute myeloid leukemia. Haematologica. 2016 Aug;101(8):932-40. doi: 10.3324/haematol.2016.142976. Epub 2016 May 12.

• Responsible Party: Yusuf Menda, Associate Professor, University of Iowa
• ClinicalTrials.gov Identifier: NCT03335670 History of Changes
• Other Study ID Numbers: 201708705; P50CA174521 ( U.S. NIH Grant/Contract )
• First Posted: November 8, 2017
• Last Update Posted: April 4, 2019
• Last Verified: April 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Individual participant data will be shared upon request to the study's principal investigator. A signed usage agreement will need to be provided.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Time Frame: After the study has been completed.
• Access Criteria: Individual participant data will be shared upon request to the study's principal investigator. A signed usage agreement will need to be provided.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Yusuf Menda, University of Iowa:

68Ga-pentixafor; (68Ga)pentixafor; Gallium Radioisotopes; CXCR4

Additional relevant MeSH terms:

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue