- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04469127
A Phase I/II Multicenter, Open-Label Study of Lu-177-DOTAGA-IAC, for the Treatment of Angiogenic Breast Cancer Patients. (Heroine01)
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Stanley Satz, Ph.D.
- Phone Number: 561-561 286-6842
- Email: ssatz@advancedimagingprojects.com
Study Contact Backup
- Name: Rose Satz
- Phone Number: 5617578666
- Email: rsatz@advancedimagingprojects.com
Study Locations
-
-
-
Chandigarh, India, 160 012
- Postgraduate Institute of Medical and Research
-
Contact:
- Br Mittal, M.D./Ph.D.
- Phone Number: +911722756722
- Email: brmittal@yahoo.com
-
-
-
-
-
Johannesburg, South Africa, 2193
- CM Johannesburg Academic Hospital, University of the Witwatersrand
-
Contact:
- Mboyo-Di-Tamba Vangu, M.D./Ph.D.
- Phone Number: +271120483608
- Email: mboyo-ditamba.vangu@wits.ac.za
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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).
- Baseline LVEF ≥40% measured using echocardiogram or equilibrium isotopic ventriculography
Exclusion Criteria:
- 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.
Additional inclusion criterion for measure human dosimetry
- Unable to comply with the requirements of the dosimetry imaging protocol
- Due to potential radiation safety issues, patients with urinary drainage or diversion (e.g., in-dwelling Foley™ catheter, ureteroileostomy, etc.) will not be enrolled.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm 1
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. |
Study participants be administered therapeutic doses of Lutetium-177-DOTAGA-IAC up to three treatments spaced 4 weeks apart.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Specific Aims 5
Time Frame: 6 months
|
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
|
Specific Aim 2
Time Frame: 6 months
|
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
Time Frame: 6 months
|
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
Time Frame: 6 months
|
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 Aim 1
Time Frame: 6 months
|
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
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Specific Aim 1
Time Frame: 6-12 Months
|
To determine the Objective Response Rate (ORR) of fractionated administration of Lu-177-DOTAGA-IAC.Percentage of subjects still alive.
Percentage of subjects who achieved a best overall response of Complete Response [CR] or Partial Response [PR] according to RECIST 5.0 Criteria.
|
6-12 Months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Stanley Satz, Ph.D., Advanced Imaging Projects
Publications and helpful links
General Publications
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 145358
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Breast Cancer Stage IV
-
University of Colorado, DenverActive, not recruitingStage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast CancerUnited States
-
Albert Einstein College of MedicineNational Cancer Institute (NCI)Active, not recruitingStage IV Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage IIIC Breast CancerUnited States
-
University of California, San FranciscoMerck Sharp & Dohme LLCTerminatedAnatomic Stage IV Breast Cancer AJCC v8 | Prognostic Stage IV Breast Cancer AJCC v8United States
-
NSABP Foundation IncCompletedBreast Cancer | Stage IV Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IIB Breast Cancer | Locally AdvancedUnited States
-
Wake Forest University Health SciencesCompletedStage I Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IIIC Breast CancerUnited States
-
University of WashingtonNational Cancer Institute (NCI)CompletedHER2-positive Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-positive Breast CancerUnited States
-
Eske Corporation S.A.CTerminatedBreast Cancer Stage IV | Breast Cancer Stage IIIA | Breast Cancer, Stage IIIBPeru
-
Indiana University School of MedicineBreast Cancer Research FoundationCompletedQuantitation of Endothelial Progenitor Cells as Markers of Tumor Angiogenesis in Breast Cancer (EPC)Breast Cancer Stage IV | Breast Cancer Stage I | Breast Cancer Stage IIUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)TerminatedHER2-positive Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast CancerUnited States
-
Roswell Park Cancer InstituteRecruitingAnatomic Stage IV Breast Cancer AJCC v8 | Prognostic Stage IV Breast Cancer AJCC v8 | Metastatic Breast CarcinomaUnited States
Clinical Trials on Lutetium-177-DOTAGA-IAC
-
OHSU Knight Cancer InstituteNovartis; Oregon Health and Science UniversityNot yet recruitingAnatomic Stage IV Breast Cancer AJCC v8 | Prognostic Stage IV Breast Cancer AJCC v8 | Recurrent Breast Carcinoma | Metastatic Breast CarcinomaUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)WithdrawnMetastatic Adrenal Gland Pheochromocytoma | Stage III Thyroid Gland Medullary Carcinoma AJCC v8 | Stage IV Thyroid Gland Medullary Carcinoma AJCC v8 | Locally Advanced Adrenal Gland Pheochromocytoma | Locally Advanced Paraganglioma | Metastatic Paraganglioma | Metastatic Parathyroid Gland Carcinoma and other conditionsUnited States
-
Radboud University Medical CenterDutch Cancer SocietyCompletedAdenoid Cystic Carcinoma | Salivary Gland Cancer | Salivary Duct CarcinomaNetherlands
-
Bivision Pharmaceuticals, Inc.Recruiting
-
Novartis PharmaceuticalsCompletedNeuroendocrine TumorUnited States
-
Peter MacCallum Cancer Centre, AustraliaRecruitingProstate Cancer | Metastatic Castration-resistant Prostate Cancer | mCRPCAustralia
-
Ralph NULL SalloumChildren's Hospital Medical Center, CincinnatiRecruitingHigh Grade Glioma | Medulloblastoma | Meningioma | Anaplastic Ependymoma | Recurrent Malignant Glioma | Recurrent Medulloblastoma | Refractory Malignant Glioma | Refractory Medulloblastoma | Recurrent Diffuse Intrinsic Pontine Glioma | Recurrent Primary Central Nervous System Neoplasm | Refractory Primary... and other conditionsUnited States
-
University Health Network, TorontoCancer Care Ontario; Ozmosis Research Inc.; Canadian Molecular Imaging Probe...Active, not recruitingNeuroendocrine TumorsCanada
-
Lawson Health Research InstituteActive, not recruiting
-
Marnix LamCompletedNeuroendocrine Tumors | Liver MetastasesNetherlands