Breast Cancer Stage IVPhase 1/2Heroine01NCT04469127
A Phase I/II Multicenter, Open-Label Study of Lu-177-DOTAGA-IAC, for the Treatment of Angiogenic Breast Cancer Patients.
A Phase 1/2 study testing Lutetium-177-DOTAGA-IAC in people with Breast Cancer Stage IV, run by Advanced Imaging Projects, LLC at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Breast Cancer Stage IV
- What is being tested?
- Lutetium-177-DOTAGA-IAC
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 30 Sep 2024to 30 Aug 2025
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
India1 site
Postgraduate Institute of Medical and Research
Chandigarh, 160 012
Br Mittal, M.D./Ph.D., +911722756722, brmittal@yahoo.com
South Africa1 site
CM Johannesburg Academic Hospital, University of the Witwatersrand
Johannesburg, 2193
Mboyo-Di-Tamba Vangu, M.D./Ph.D., +271120483608, mboyo-ditamba.vangu@wits.ac.za
About this study
Official title: 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.
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.
Read the detailed description
This is a prospective, Phase I/II multi-center, interventional open-label study in a total of up to 100 subjects with angiogenic breast cancer. Phase I is to assess the safety and adequacy of a dose of HurlutinTM Lu-177 for up to three cycles, at 4-week intervals. It will include a dose expansion cohort of up to 20 patients. Phase II is to demonstrate the safety, dose adequacy, anti-tumor activity and efficacy of tumor targeted therapy using Lutetium-177-DOTAGA-IAC , as a second- or third-line treatment to extend survival and improve the quality of life of patients with angiogenic breast cancer.
- Conditions
- Breast Cancer Stage IV
- Being tested
- Lutetium-177-DOTAGA-IAC
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lutetium-177-DOTAGA-IACDrug
Study participants be administered therapeutic doses of Lutetium-177-DOTAGA-IAC up to three treatments spaced 4 weeks apart.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Lutetium-177-DOTAGA-IAC |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 6 months
Secondary outcomes (1)
Specific Aim 1
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.
Measured: 6-12 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2020
- Study start30 Sep 2024 (estimated)
- Primary completion30 Aug 2025 (estimated)
- Study completion30 Aug 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast Cancer Stage IVStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Advanced Imaging Projects, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University of Witwatersrand, South Africa, Postgraduate Institute of Medical and Research
- Responsible party
- Sponsor
- Investigators
- Stanley Satz, Ph.D., Study director, Advanced Imaging Projects
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04469127
- Sponsor's protocol ID
- 145358
- Acronym
- Heroine01
- Status last verified
- Apr 2024
- First submitted
- 30 Jun 2020
- Last updated
- 10 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD is to be shared with researchers
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.
PubMed 25945808Kim 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.
PubMed 22853992
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT04469127
- Acronym / sponsor ID
- Heroine01 / 145358
- Conditions
- Breast Cancer Stage IV
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Advanced Imaging Projects, LLCIndustry (pharma, biotech, devices)
- Collaborators
- University of Witwatersrand, South Africa, Postgraduate Institute of Medical and Research
- Study start
- 30 Sep 2024 (estimated)
- Primary completion
- 30 Aug 2025 (estimated)
- Study completion
- 30 Aug 2025 (estimated)
- First posted
- 13 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a prospective, Phase I/II multi-center, interventional open-label study in a total of up to 100 subjects with angiogenic breast cancer. Phase I is to assess the safety and adequacy of a dose of HurlutinTM Lu-177 for up to three cycles, at 4-week intervals. It will include a dose expansion cohort of up to 20 patients. Phase II is to demonstrate the safety, dose adequacy, anti-tumor activity and efficacy of tumor targeted therapy using Lutetium-177-DOTAGA-IAC , as a second- or third-line treatment to extend survival and improve the quality of life of patients with angiogenic breast cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: Lutetium-177-DOTAGA-IACSingle 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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.
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lutetium-177-DOTAGA-IACStudy participants be administered therapeutic doses of Lutetium-177-DOTAGA-IAC up to three treatments spaced 4 weeks apart. | Drug | Arm 1 |
Primary outcome
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.
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
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.
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.
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.
1 secondary outcome
Specific Aim 1
Time frame: 6-12 Months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2024.
- Results publication: PubMed 25945808Baum 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.
- Results publication: PubMed 22853992Kim 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.
- Individual participant dataSharing planned: Yes. IPD is to be shared with researchers
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stanley Satz, Ph.D. study director
Advanced Imaging Projects
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Lutetium-177-DOTAGA-IAC in people with Breast Cancer Stage IV, run by Advanced Imaging Projects, LLC at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in India, South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Stanley Satz, Ph.D. (561-561 286-6842, ssatz@advancedimagingprojects.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Specific Aim 1 (time frame: 6 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04469127, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Apr 2024.