A Phase I/II Multicenter, Open-Label Study of Lu-177-DOTAGA-IAC, for the Treatment of Angiogenic Breast Cancer Patients.

NCT04469127 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 145358
• Study Type: interventional
• Target: 100
• Locations: 2 countries
• Sites: 2

Brief Summary

This study is a Phase I/II clinical evaluation of a new investigational agent, Lutetium-177-DOTAGA-IAC (HurlutinTM Lu-177) to treat patients with unresectable angiogenic breast cancer who have previously been treated with at least one prior line of therapy.

Conditions

Breast Cancer Stage IV

Outcome Measures

Primary Outcomes (5)

• Specific Aim 1

  To determine the safety and tolerability of fractionated administrations of 3 cycles of Lu-177-DOTAGA-IAC administered with 4 weeks between cycles in patients with high-risk Angiogenic Breast Cancer who have progressed on, or do not tolerate, best standard-of-care treatment. Measurements used to assess the safety, tolerability and side-effects profile will include adverse events of any grade, grade 3 and 4 adverse events, withdrawals due to adverse events and dose reductions due to adverse events. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v.5.0) will be used to evaluate AE grade.

  6 months

• Specific Aim 2

  To determine the pharmacokinetics (PK) of Lu-177-DOTAGA-IAC. The area under the Time vs. Concentration curve for Lu-177-DOTAGA-IAC from injection to 72 h

  6 months

• Specific Aim 3

  To determine the whole-body biodistribution of Lu-177-DOTAGA-IAC. Percent injected dose per gram of tissue (%ID)/gm of Lu-177-DOTAGA-IAC.

  6 months

• Specific Aim 4

  To determine the radiation dosimetry of Lu-177-DOTAGA-IAC.Time points will be 0 and 120, 30 and 150, 60 and 180, or 90 and 210 min after injection.Time integrals of activity will be entered into the (Organ Level INternal Dose Assessment/ EXponential Modeling) OLINDA/EXM software.

  6 months

• Specific Aims 5

  To determine optimum cumulative fractionated administered dose. Increase dose range if a DLT (Dose Limiting Toxicity) develops or they do not have a T/B ratio \>1.

  6 months

Secondary Outcomes (1)

• Specific Aim 1

  6-12 Months

Study Arms (1)

Arm 1

EXPERIMENTAL

Single Arm study Lu-177-DOTAGA-IAC (intracutaneous) Dosage and Dose Escalation Frequency: Cohort 1: 75 mCi x 3 (maximum cumulative administered activity, 225mCi) + 100 μgr IAC Cohort 2: 150 mCi x 3 (maximum cumulative administered activity, 450mCi) + 100 μgr IAC Cohort 3: 200 mCi x 3 (maximum cumulative administered activity, 600mCi) + 100 μgr IAC Three cycles each 4 weeks apart.

Drug: Lutetium-177-DOTAGA-IAC

Interventions

Lutetium-177-DOTAGA-IAC DRUG

Study participants be administered therapeutic doses of Lutetium-177-DOTAGA-IAC up to three treatments spaced 4 weeks apart.

Arm 1

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Angiogenic breast tumor by immunohistochemistry confirmation.
• Positive scan with PET/CT imaging with 18F-FET PET/CT.
• Tumor progression resistant or refractory to at least one prior lines of standard chemotherapy which include trastuzumab and/or Ado-trastuzumab with or without chemotherapy agents.
• At least 18 years of age
• The patient is able and willing to provide informed consent and to comply with the requirements of this trial protocol.
• ECOG score ≤3
• Females of childbearing potential must have a negative serum pregnancy test or have had an intervention that renders pregnancy not possible
• Adequate organ function, defined as:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/mL.
• Hemoglobin (Hb) ≥10 g/dl (transfusion or use of EPO is permitted).
• Platelets \> 100,000/mm3
• Creatinine ≤ 1.5 x upper limit of normal (ULN)
• AST or ALT ≤ 2.5 x ULN (or ≤5 x ULN in case of liver metastasis)
• Alkaline phosphatase ≤2.5 x ULN. Alkaline phosphatase may be more than 2.5 x ULN only in the case of bone metastases, and AST and ALT less than 1.5 x ULN.
• Total bilirubin ≤1.5 mg/dl (higher bilirubin levels are permitted if the patient has Gilbert's syndrome).

You may not qualify if:

• Previously received external beam irradiation that includes more than 30% of bone marrow
• Previously received external beam irradiation to a field that one kidney.
• Previously received external beam irradiation to a field that includes the only known lesion.
• Any uncontrolled significant medical, psychiatric or surgical condition or laboratory finding that would pose a risk to subject safety or interfere with study participation or interpretation of individual subject results.
• Nephrectomy, renal transplant or concomitant nephrotoxic therapy putting the subject at high risk of renal toxicity during the study.
• eGFR ≤ 50.
• Bone metastases are the only known lesions.
• Patients with a body weight of 400 pounds or more or not able to enter the bore of the PET/CT scanner due to BMI, because of the compromise in image quality with CT, PET/CT and MRI that will result.
• Inability to lie still for the entire imaging time (e.g., cough, severe arthritis, etc.).
• Use of any other investigational therapeutic product within 30 days prior to dosing or known requirement for any other investigational agent prior to completion of all scheduled study assessments.
• Recognized concurrent active infection.
• Received any live (attenuated) vaccines within 30 days prior to Visit.
• Recent or chronic treatment with medium-to-high-dose intravenous corticosteroids (methylprednisolone 60 mg/day or hydrocortisone 300 mg/day) within 8 weeks prior to Visit or oral corticosteroids of more than 20 mg prednisone (or equivalent) within 30 days prior to Visit
• Any unresolved NCI-CTCAE Grade 2 or higher (except alopecia) from previous anti-tumour treatment and/or medical/surgical procedures/interventions.
• Unable to comply with the requirements of the dosimetry imaging protocol

Sponsors & Collaborators

• Advanced Imaging Projects, LLC: lead
• University of Witwatersrand, South Africa: collaborator
• Postgraduate Institute of Medical and Research: collaborator

Study Sites (2)

Postgraduate Institute of Medical and Research

Chandigarh, 160 012, India

Location

CM Johannesburg Academic Hospital, University of the Witwatersrand

Johannesburg, 2193, South Africa

Location

Related Publications (2)

• Baum RP, Kulkarni HR, Muller D, Satz S, Danthi N, Kim YS, Brechbiel MW. First-In-Human Study Demonstrating Tumor-Angiogenesis by PET/CT Imaging with (68)Ga-NODAGA-THERANOST, a High-Affinity Peptidomimetic for alphavbeta3 Integrin Receptor Targeting. Cancer Biother Radiopharm. 2015 May;30(4):152-9. doi: 10.1089/cbr.2014.1747.

  PMID: 25945808 RESULT

• Kim YS, Nwe K, Milenic DE, Brechbiel MW, Satz S, Baidoo KE. Synthesis and characterization of alphavbeta(3)-targeting peptidomimetic chelate conjugates for PET and SPECT imaging. Bioorg Med Chem Lett. 2012 Sep 1;22(17):5517-22. doi: 10.1016/j.bmcl.2012.07.024. Epub 2012 Jul 14.

  PMID: 22853992 RESULT

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Stanley Satz, Ph.D.

  Advanced Imaging Projects

  STUDY DIRECTOR

Central Study Contacts

Stanley Satz, Ph.D.

CONTACT

561-561 286-6842; ssatz@advancedimagingprojects.com

Rose Satz

CONTACT

5617578666; rsatz@advancedimagingprojects.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2020
• First Posted: July 13, 2020
• Study Start: September 30, 2024
• Primary Completion: August 30, 2025
• Study Completion: August 30, 2025
• Last Updated: April 10, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: 1 Yr.
• Access Criteria: Contact Sponsor

Locations

ZA (1); IN (1)