Evaluation of Somatostatin Receptor Expression in PET 68Ga-DOTATOC in Patients Followed for Metastatic Breast Cancer (DOTABREAST)

DOTABREAST: Evaluation of Somatostatin Receptor Expression in PET 68Ga-DOTATOC in Patients Followed for Metastatic Breast Cancer

This is a prospective, monocentric, non-controlled, non-randomized, open-label, interventional study.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer Metastatic
• Intervention / Treatment: Drug: 68Ga-DOTATOC

Detailed Description

In women, breast cancer is the 1st largest cancer and accounted for 31% of new cancer cases in women in 2017. With 11,913 deaths in 2015, breast cancer is the 1st largest cancer death in women (19%) and the 3rd largest cancer death (men and women included) after lung and colorectal cancer. At initial diagnosis at any stage, approximately 31% of patients have regional lymph node involvement and 5 to 10% present metastatic involvement from the outset. Progression to a metastatic form occurs in about 20% of cases. The risk of metastatic evolution is variable depending on the histological subtype and is a major prognostic event directly impacting overall survival. DOTATOC-68Ga PET scans allows in vivo evaluation of SST2 somatostatin receptor expression. Its use is widely validated in clinical practice for the assessment of extension of neuroendocrine tumors. It is also being used to evaluate the feasibility of SST2-targeted internal radiotherapy therapy with Lutathera (177Lu-Oxodotreotide) in patients with metastatic small intestine neuroendocrine tumours.

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Marine Faure; Phone Number: 0476766872; Email: MFaure6@chu-grenoble.fr
• Study Contact Backup: Name: Pierre PITTET; Phone Number: 0476766872; Email: ppittet@chu-grenoble.fr

Study Locations

• France
  • Grenoble, France, 38043
    • Recruiting
    • Chu Grenoble Alpes
    • Contact: Loic DJAILEB, MD, PHD; Phone Number: 0476765455; Email: ldjaileb@chu-grenoble.fr
    • Contact: Emmanuelle JACQUET, MD, PHD; Phone Number: 0476765451; Email: ejacquet1@chu-grenoble.fr
    • Contact: Loic DJAILEB, MD, PHD
    • Contact: Emmanuelle JACQUET, MD, PHD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age over 18
• Patients with metastatic breast cancer who have completed at least one first line of systemic therapy for metastatic breast cancer
• Patient labeled on the primary lesion ER+HER2- (20)
• Presence of metastatic liver and bone lesions identifiable with 18F-FDG PET-Scan
• Presence of at least 10 identifiable secondary lesions in 18F-FDG PET-Scan
• No therapeutic change between 18F-FDG PET-Scan and 68Ga-DOTATOC PET-Scan.
• Performing the PET scan with 68Ga-DOTATOC within a maximum of 21 days after the 18F-FDG PET-Scan
• Person affiliated to or benefiting from social security
• Person who has given written informed consent

Exclusion Criteria:

• Patients followed or with history of other active neoplastic pathology (including neuroendocrine tumor)
• Known allergy to 68Ga-DOTATOC or its excipients
• Subject refusing to sign the consent to participate
• Minor subject
• Subject excluded from another study
• Persons referred to Articles L1121-5 to L1121-8 of the Public Health Code (CSP)
• Subject cannot be contacted in case of emergency

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Performing a 68Ga-Dotatoc PET scan in patients followed for metastatic breast cancer.; Prescreening of the patient followed for metastatic breast cancer during the routine care; V1 Selection: Patient's selection in the Nuclear Medicin or Oncology department; V2 Inclusion: The day of the 68Ga-Dotatoc PET scan in the Nuclear Medicin department; V3 End of study visit, the same day after the 68Ga-Dotatoc PET scan.

Drug: 68Ga-DOTATOC; Slow direct intravenous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of lesions expressing SST2 receptors in 68Ga-DOTATOC in patients followed for metastatic breast cancer	Krenning Score >2	Baseline (during the PET examination)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distribution of SST2 receptor overexpression by 68Ga-DOTATOC PET compared to 18F-FDG PET lesions.	Lesion-by-lesion analysis of lesion fixation intensity on 68Ga-DOTATOC PET (Krenning score (requires comparison to the liver and spleen (or kidney if not applicable) and calculated between 0 and 4) and PET quantification parameters).	Baseline (during the PET examination)
Disease proportion with SST2 receptor overexpression by 68Ga-DOTATOC PET compared to known metastatic disease by 18F-FDG PET	Disease volume per patient with overexpression of SST2 receptors in 68Ga-DOTATOC PET compared to metabolic volume in 18F-FDG PET	Baseline (during the PET examination)
Expression of SST2 receptors of lesions as a function of different metastatic sites, via the Krenning score	Krenning Score (from 0 to 4, 0 is none and 4 is greater than that of spleen, lesion with very low or no DOTATOC uptake (Score 0 or 1) are consider as a negative lesion, lesion with DOTATOC uptake ≥ 2 are consider as a positive lesion)	Baseline (during the PET examination)
Expression of SST2 receptors of lesions as a function of different metastatic sites, via the PET quantification parameters.	PET quantification parameters (SUV max and SUV mean)	Baseline (during the PET examination)
Correlation between the metabolic activity of 18F-FDG PET lesions and the expression of SST2 receptors in 68Ga-DOTATOC PET per lesion and per patient.	Comparison between 68Ga-DOTATOC PET and 18F-FDG PET (Krenning score and PET quantification parameter) per lesion and per patient.	Baseline (during the PET examination)
Clinica predictors of overexpression of SST2 receptors in 68Ga-DOTATOC PET per patient	Clinical data prior to PET at 68Ga-DOTATOC per patient	Baseline (during the PET examination)
Biological predictors of overexpression of SST2 receptors in 68Ga-DOTATOC PET per patient	Biological data prior to PET at 68Ga-DOTATOC per patient	Baseline (during the PET examination)
Histological predictors of overexpression of SST2 receptors in 68Ga-DOTATOC PET per patient	Histological data prior to PET at 68Ga-DOTATOC per patient	Baseline (during the PET examination)
Imaging predictors of overexpression of SST2 receptors in 68Ga-DOTATOC PET per patient	Imaging data prior to PET at 68Ga-DOTATOC per patient	Baseline (during the PET examination)
Clinical predictors of overexpression of SST2 receptors in 68Ga-DOTATOC PET by lesion	Clinical data prior to PET at 68Ga-DOTATOC per lesion	Baseline (during the PET examination)
Biological predictors of overexpression of SST2 receptors in 68Ga-DOTATOC PET by lesion	Biological data prior to PET at 68Ga-DOTATOC per lesion	Baseline (during the PET examination)
Histological predictors of overexpression of SST2 receptors in 68Ga-DOTATOC PET by lesion	Histological data prior to PET at 68Ga-DOTATOC per lesion	Baseline (during the PET examination)
Imaging predictors of overexpression of SST2 receptors in 68Ga-DOTATOC PET by lesion	Imaging data prior to PET at 68Ga-DOTATOC per lesion	Baseline (during the PET examination)

Collaborators and Investigators

• Sponsor: University Hospital, Grenoble
• Investigators: Principal Investigator: Loic DJAILEB, Chu Grenoble Alpes

Publications and helpful links

General Publications

• Virgolini I, Ambrosini V, Bomanji JB, Baum RP, Fanti S, Gabriel M, Papathanasiou ND, Pepe G, Oyen W, De Cristoforo C, Chiti A. Procedure guidelines for PET/CT tumour imaging with 68Ga-DOTA-conjugated peptides: 68Ga-DOTA-TOC, 68Ga-DOTA-NOC, 68Ga-DOTA-TATE. Eur J Nucl Med Mol Imaging. 2010 Oct;37(10):2004-10. doi: 10.1007/s00259-010-1512-3.
• Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, Mittra E, Kunz PL, Kulke MH, Jacene H, Bushnell D, O'Dorisio TM, Baum RP, Kulkarni HR, Caplin M, Lebtahi R, Hobday T, Delpassand E, Van Cutsem E, Benson A, Srirajaskanthan R, Pavel M, Mora J, Berlin J, Grande E, Reed N, Seregni E, Oberg K, Lopera Sierra M, Santoro P, Thevenet T, Erion JL, Ruszniewski P, Kwekkeboom D, Krenning E; NETTER-1 Trial Investigators. Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors. N Engl J Med. 2017 Jan 12;376(2):125-135. doi: 10.1056/NEJMoa1607427.
• Frati A, Rouzier R, Lesieur B, Werkoff G, Antoine M, Rodenas A, Darai E, Chereau E. Expression of somatostatin type-2 and -4 receptor and correlation with histological type in breast cancer. Anticancer Res. 2014 Aug;34(8):3997-4003.
• Dude I, Zhang Z, Rousseau J, Hundal-Jabal N, Colpo N, Merkens H, Lin KS, Benard F. Evaluation of agonist and antagonist radioligands for somatostatin receptor imaging of breast cancer using positron emission tomography. EJNMMI Radiopharm Chem. 2017;2(1):4. doi: 10.1186/s41181-017-0023-y. Epub 2017 Apr 17.
• Sollini M, Erba PA, Fraternali A, Casali M, Di Paolo ML, Froio A, Frasoldati A, Versari A. PET and PET/CT with 68gallium-labeled somatostatin analogues in Non GEP-NETs Tumors. ScientificWorldJournal. 2014 Feb 13;2014:194123. doi: 10.1155/2014/194123. eCollection 2014.
• Dalm SU, Haeck J, Doeswijk GN, de Blois E, de Jong M, van Deurzen CHM. SSTR-Mediated Imaging in Breast Cancer: Is There a Role for Radiolabeled Somatostatin Receptor Antagonists? J Nucl Med. 2017 Oct;58(10):1609-1614. doi: 10.2967/jnumed.116.189035. Epub 2017 Apr 27.
• Dalm SU, Schrijver WA, Sieuwerts AM, Look MP, Ziel-van der Made AC, de Weerd V, Martens JW, van Diest PJ, de Jong M, van Deurzen CH. Prospects of Targeting the Gastrin Releasing Peptide Receptor and Somatostatin Receptor 2 for Nuclear Imaging and Therapy in Metastatic Breast Cancer. PLoS One. 2017 Jan 20;12(1):e0170536. doi: 10.1371/journal.pone.0170536. eCollection 2017.
• Hope TA, Bergsland EK, Bozkurt MF, Graham M, Heaney AP, Herrmann K, Howe JR, Kulke MH, Kunz PL, Mailman J, May L, Metz DC, Millo C, O'Dorisio S, Reidy-Lagunes DL, Soulen MC, Strosberg JR. Appropriate Use Criteria for Somatostatin Receptor PET Imaging in Neuroendocrine Tumors. J Nucl Med. 2018 Jan;59(1):66-74. doi: 10.2967/jnumed.117.202275. Epub 2017 Oct 12. No abstract available.
• Ozelius L, Kramer PL, Moskowitz CB, Kwiatkowski DJ, Brin MF, Bressman SB, Schuback DE, Falk CT, Risch N, de Leon D, et al. Human gene for torsion dystonia located on chromosome 9q32-q34. Neuron. 1989 May;2(5):1427-34. doi: 10.1016/0896-6273(89)90188-8.

Helpful Links

• Fiche info - SOMAKIT TOC 40 microgrammes, trousse pour préparation radiopharmaceutique - Base de données publique des médicaments.
• 111In-Pentetreotide Scintigraphy Versus 68Ga-DOTATATE PET: Impact on Krenning Scores and Effect of Tumor Burden

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2025
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: April 20, 2023
• First Submitted That Met QC Criteria: September 20, 2024
• First Posted (Actual): September 25, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 27, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: DOTATOC; 68Ga-DOTATOC; Breast Cancer Metastatic; PET-SCAN; Somatostatin Receptor Expression; Nuclear Oncology; 177-Lu-Oxodotreotide
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Edotreotide
• Other Study ID Numbers: 38RC21.0432

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No