Avidination for RadionuclideTHerapy in Nonpalpable Breast Cancer (ARTHE)

Avidination for Radionuclide THerapy (A.R.THE.) in Nonpalpable Breast Cancer

This is an interventional, open-label, non comparative phase 2 trial enrolling patients with nonpalpable breast cancer

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Avidin-biotin-Dota-90Y

Detailed Description

Nonpalpable breast lesions (NPBLs) represent approximately 30% of the overall tumoral breast lesions undergoing surgery. The Vacuum-Assisted Breast Biopsy (VABB) is a device for needle breast biopsy usefully applied in NPBL. The procedure is highly effective for the diagnosis of NPBLs, with minimal negative effects. The specimen volume obtained through this procedure is great enough to replace the diagnostic surgical excisional biopsy and frozen section intraoperative examination. Biopsies obtained through this method sometimes allow the complete excision of the lesion, representing a valid alternative to the excisional biopsy in case of benign lesion less than 15 mm in size.

After VABB procedure about 10-30% of patients have a complete removal of the neoplastic lesion. About 30% of patients are disease free after surgery because the lesion has been totally removed through diagnostic VABB procedure. The rationale of this project is to treat residual microscopic disease through a radionuclide therapy. Our idea is to administer, following VABB procedure, an avidin-biotin-DOTA-90Y (where DOTA stands for 1,4,7,10-tetra-azacyclododecane-N,N',N'',N'''-tetraacetic acid and Y stands for yttrium) compound into the lesion site in order to eliminate residual tumour cells. The ARTHE approach should increase the rate of disease free cases after excisional biopsy.

The primary objective of this open-label phase I trial is to evaluate the safety of avidin-biotin-DOTA-90Y combination in patients with nonpalpable breast cancer undergoing Vacuum-Assisted- Breast- Biopsy (VABB). The co-primary objective is the evaluation of the preliminary anti-tumor activity of the treatment. The secondary objective is to evaluate the dosimetry and biodistribution of avidin-biotin-DOTA-90Y after loco-regional injection under ultrasound guidance.

ARTHE procedure consists of the ultrasound guided injection of Avidin into the breast tissue corresponding to VABB site followed by an injection of Biotin-DOTA-90Y. The injected Biotin-DOTA-90Y will be in a range 28-126 MBq (megabecquerel) (0.2- 0.3 mL, specific activity of 3.7 GBq/mg) (gigabequerel/milligrams). The investigators will inject 6-10 mg of avidin in a volume of 0.3-0.5 mL, followed by biotin-DOTA-90Y immediately after avidin injection.

The hypothesis that a treatment with avidin-biotin-DOTA-90Y is able to destroy residual cancer cells after VABB will be verified by surgery.

The duration of ARTHE procedure is 3 days, including dosimetry evaluation. Patients will receive conservative surgical treatment (4-7 weeks from ARTHE treatment).

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Oriana Nanni; Phone Number: 0543739266; Email: oriana.nanni@irst.emr.it
• Study Contact Backup: Name: Bernadette Vertogen; Phone Number: 0544286058; Email: bernadette.vertogen@irst.emr.it

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients must have diagnosis of occult breast cancer on the basis of mammography (BIRADS's score 4 - 5)/ultrasound (SCORE 4-5).
2. Pathological diagnosis of in situ or infiltrating breast carcinoma (any histotype)
3. Tumor size >5 and ≤15 mm (at least 13 mm from the skin surface)
4. Female, 18≤age≤75.
5. ECOG (Eastern Cooperative Oncology Group) performance status <2
6. Patients scheduled to receive conservative surgical treatment
7. The effects of investigational medicinal product (IMP) on the developing human fetus are unknown. For this reason and because IMP in this trial is known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 4 months after completion. See Appendix E for the "Recommendations related to contraception and pregnancy testing in clinical trials". Should a woman become pregnant or suspect she is pregnant, she should inform her treating physician immediately.
8. Participant is willing and able to give informed consent for participation in the study.

Exclusion Criteria:

1. Histotype different from carcinoma
2. Paget carcinoma
3. Lesions located near to axilla region or skin <13 mm
4. Ongoing pregnancy or breastfeeding
5. Previous treatment with avidin
6. Referred allergy to eggs or latex
7. Patients with metastases should be excluded from this clinical trial.
8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
9. Patients with previous radiotherapy and/or operation on the same breast, with diffuse microcalcifications will be excluded.
10. Patients with known BRCA (BReast CAncer gene), PALB2 (Partner and Localizer of BRCA2) and CHECK2 (Checkpoint Kinase 2) mutations, grade 3 risk profile or indication to perform a test for germline mutations based on disease characteristics
11. Multifocal tumors are not eligible for the study.
12. History of malignancy within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS (overall survival) rate >90%).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: Avidin-biotin-Dota-90Y; The total planned enrollment for this study is up to approximately 52 patients for Part 1 (dose-escalation) and Part 2 (dose expansion). Up to 18 patients will be enrolled in Part 1 (depending on dose-escalation) and 40 patients in dose expansion in Part 2. The 6 patients evaluated for dosimetry in Part 1 will also be evaluated in part 2.	Drug: Avidin-biotin-Dota-90Y; Within 7-8 days after the VABB procedure, 6-10 mg avidin in 1 ml saline will be administered at the site of the occult carcinoma. Subsequently, 90Y DOTA-biotin in the range of 28-57-126 MBq (3 activity levels investigated) will be injected locally immediately after avidin injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of avidin-biotin-Dota-90Y	The primary endpoint is the systemic toxicity evaluated according to NCI-CTCAE (The U.S. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events) Version 5.0	4-7 weeks
Anti-tumor activity of avidin-biotin-Dota-90Y	The co-primary endpoint is the evaluation of the complete pathological response rate, defined as the absence of residual invasive and in situ cancer or DCIS (ductal carcinoma in situ), on hematoxylin and eosin evaluation of the complete resected breast specimen and of all sampled regional lymph nodes (i.e., ypT0 ypN0 in the current AJCC staging system).	4-7 weeks
Safety of avidin-biotin-Dota-90Y	The primary endpoint is the local toxicity evaluated according to Radiation Therapy Oncology Group (RTOG) scale. According to the RTOG scale grades range from 0 to 5, where 0 represents no change over baseline and 5 represents any toxicity which causes death.	4-7 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-response	Serial PET (positron emission computed tomography)/CT (computerized tomography) scan will be performed at defined time intervals after radiopharmaceutical administration. The number of PET/CT scans depends on the presence of wash-out documented by the whole body image acquired with SPECT/CT scanner. A dedicated software will be used to segment the region of interest, to quantify the activity inside the target region, and to estimate the number of disintegrations, that is the input data for absorbed dose calculation. For the tumor absorbed dose calculation, the spherical volume approximation is used with a uniform activity distribution. The tumor mass is estimated from the CT scan. From the computed data, a detailed report relative to absorbed dose to the tumor and neighboring organs treated with avidin-biotin-DOTA-90Y will be prepared, in order to provide a dose-response relationship for toxicity avoidance.	48-72 hours after injection
Biodistribution	The whole-body image will be used to evaluate 90Y biodistribution in the body and to verify that the injected activity is really localized in the breast tissue. In this case, the treatment can be considered as locoregional, with the uptake concentrated in a limited region of the breast, without the involvement of other organs. To evaluate the assumption of a localized uptake in the tumor lesion, the patients will undergo just one PET/ CT scan.	1-3 hours after injection

Collaborators and Investigators

• Sponsor: Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
• Investigators: Principal Investigator: Federica Matteucci, Irccs Irst

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: April 17, 2024
• First Submitted That Met QC Criteria: April 26, 2024
• First Posted (Actual): April 30, 2024

Study Record Updates

• Last Update Posted (Actual): May 6, 2024
• Last Update Submitted That Met QC Criteria: May 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: non-palpable breast lesions; infiltrating breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Biotin
• Other Study ID Numbers: IRST174.14

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