Clinical Trials /

A Study of AIP-303 in HER2 Positive Breast Cancer and/or Metastatic Breast Cancer Patients

NCT04469127

Description:

The HEROINE-Breast01 study is a Phase I/II clinical study of a new investigational agent, AIP-303 to help patients with metastatic or unresectable HER2-positive breast cancer and for women with previously treated HER2 positive breast cancer who have gone through at least two prior lines of treatment and received other HER-2-targeted drugs, Trastuzumab or Ado-Trastuzumab and chemotherapy as part of earlier treatments and who have progressed on one or more available therapies. AIP-303 may help slow down tumor growth and this might improve outcomes and quality-of-life for these patients.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of AIP-303 in HER2 Positive Breast Cancer and/or Metastatic Breast Cancer Patients
  • Official Title: A Phase I/II Multicenter, Open-Label Study of AIP-303, for HER2-Positive Unresectable and/or Metastatic Breast Cancer Patients Resistant or Refractory to Trastuzumab or Ado-Trastuzumab and Chemotherapy (Heroine-Breast 01)

Clinical Trial IDs

  • ORG STUDY ID: 145358
  • NCT ID: NCT04469127

Conditions

  • HER2 Positive Breast Cancer

Interventions

DrugSynonymsArms
AIP-303Arm 1

Purpose

The HEROINE-Breast01 study is a Phase I/II clinical study of a new investigational agent, AIP-303 to help patients with metastatic or unresectable HER2-positive breast cancer and for women with previously treated HER2 positive breast cancer who have gone through at least two prior lines of treatment and received other HER-2-targeted drugs, Trastuzumab or Ado-Trastuzumab and chemotherapy as part of earlier treatments and who have progressed on one or more available therapies. AIP-303 may help slow down tumor growth and this might improve outcomes and quality-of-life for these patients.

Detailed Description

      This is a prospective, Phase I/II, multi-center, open-label study in a total of 150 subjects
      with HER2 Positive Breast cancer tumors. Eligible participants will undergo baseline
      assessments at enrollment. Study participants be administered therapeutic doses of AIP-303 up
      to four treatments spaced 8 weeks apart and a CT scan immediately after. An AIP 301 Ga-68
      PET/CT scan will be performed four weeks before and four weeks after the initial dose of the
      AIP-303. An IEC will review the protocol and any amendments and advertisements used for
      recruitment. The IEC will review the patient information sheet and the informed consent form,
      their updates (if any), and any written materials given to the patients. A list of all IECs
      to which the protocol has been submitted and the name of the committee chairmen will be
      included in the clinical trial report.
    

Trial Arms

NameTypeDescriptionInterventions
Arm 1ExperimentalSingle Arm study
  • AIP-303

Eligibility Criteria

        Inclusion Criteria:

          -  • Patients with HER2+ metastatic solid tumors (may be 3+ by immunohistochemistry or
             with evidence of gene amplification (>2.0) by fluorescence in situ hybridization
             (FISH))

               -  Currently experiencing tumor progression on active Trastuzumab,
                  Ado-Trastuzumab/Taxane and/or standard of care.

               -  At least 18 years of age

               -  The patient is able and willing to comply with the requirements of this trial
                  protocol.

               -  Able to provide informed consent. Karnofsky score greater than 50

               -  Females of childbearing potential must have a negative pregnancy test at
                  screening/ baseline

               -  AIP 301 positive scan define by SUV greater than 10.

               -  Adequate organ function, defined as:

                    1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L.

                    2. Hemoglobin (Hb) ≥9 g/dl (transfusion or use of EPO is permitted).

                    3. Platelets > 100,000/mm3

                    4. Creatinine ≤ 1.5 x normal value

                    5. AST or ALT ≤ 2.5 x ULN (or ≤5 x ULN in case of liver metastasis)

                    6. 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.

                    7. Total bilirubin ≤1.5 mg/dl (higher bilirubin levels are permitted if the
                       patient has Gilbert's syndrome).

               -  Baseline LVEF ≥50% measured using echocardiogram or equilibrium isotopic
                  ventriculography (MUGA).

        Exclusion Criteria:

          -  • Must not have HER2+ Brain Mets

               -  Serious underlying disease other than HER2+ breast cancer in the opinion of the
                  investigator.

               -  History of drug addiction within the last 1 year or current drug addiction or use
                  of illicit drugs.

               -  Any indication of the regular use of more than 40 grams of alcohol every day.

               -  Smokers who smoke more than 10 cigarettes per day.

               -  Known concurrent acute or chronic viral hepatitis B or C infection or human
                  immunodeficiency virus (HIV) infection.

               -  Presence or history of active tuberculosis (TB) or latent TB infection, defined
                  as 1) a positive QuantiFERON-TB Gold test at Screening, or 2) a positive T-spot
                  test within 4 weeks of visit 3 and evidence of current or previous pulmonary
                  tuberculosis by chest X-ray within 12 weeks of Visit 3.

               -  Positive immunoglobulin M antibody titers in the presence of negative
                  immunoglobulin G titers to Epstein-Barr virus (EBV).

               -  If clinical suspicion of cytomegalovirus (CMV), cytomegalovirus testing should be
                  undertaken. Subjects with intestinal mucosa biopsy positive for cytomegalovirus
                  at screening are to be excluded.

               -  Currently taking any medications other than those allowed per protocol
                  guidelines.

               -  Infections (including diverticulitis) requiring treatment with antibiotics,
                  antivirals, or antifungals within 14 days prior to Visit.

               -  Serum creatinine >3.0 mg/dL (270 μM/L)

               -  Known severe allergy or hypersensitivity to IV radiographic contrast.

               -  Use of any other investigational product or device within 30 days prior to dosing
                  or known requirement for any other investigational agent prior to completion of
                  all scheduled study assessments.

               -  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

               -  Inability to complete the needed investigational and standard-of-care imaging
                  examinations due to other reasons (severe claustrophobia, radiation phobia, etc.)

               -  Recognized concurrent active infection

               -  Previous Grade 3 or higher allergic reaction to Trastuzumab or Ado-Trastuzumab
                  that resulted in discontinuation of Trastuzumab or Ado-Trastuzumab therapy. Any
                  additional medical condition, serious intercurrent illness, or other extenuating
                  circumstance that, in the opinion of the Investigator, may significantly
                  interfere with study compliance.

               -  Moderate to severe anemia (hemoglobin <9 g/dL), or thrombocytopenia (platelet
                  count <75,000/μL), or serum creatinine >2 mg/dL.

               -  Primary or secondary immunodeficiency including neutropenia (absolute neutrophil
                  count <1500/μL); or lymphopenia (absolute lymphocyte count <500/μL).

               -  Hepatic enzyme levels more than 5 times upper limit of normal: Known clinically
                  relevant chronic liver disease.

        Impaired hepatic function in the absence of a diagnosis of primary sclerosing cholangitis
        (serum transaminases >2.5 x upper limit of normal [ULN], alkaline phosphatase >2.5 x ULN,
        or abnormalities in synthetic liver function tests judged by the investigator to be
        clinically significant), or a diagnosis of primary sclerosing cholangitis, serum
        transaminases >3 x ULN, alkaline phosphatase >3 x ULN, or abnormalities in synthetic liver
        function tests (total bilirubin >1.5 x ULN) judged by the investigator to be clinically
        significant.

          -  Received any live (attenuated) vaccines within 30 days prior to Visit.

          -  Recent 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.

          -  Peptide receptor radionuclide therapy (PRRT) at any time prior to enrolment in the
             study.

          -  Receipt of cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil within 30
             days prior to Visit.

          -  Treatment with therapeutic enema or suppository, other than required for endoscopy
             preparation, within 14 days prior to the screening endoscopy and during the remainder
             of the trial.

          -  Patients with any other significant medical, psychiatric, or surgical condition,
             currently uncontrolled by treatment, which may interfere with completion of the study
      
Maximum Eligible Age:80 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Specific Aim 1
Time Frame:6 Months
Safety Issue:
Description:Demonstrate safety, tolerability and side-effects of the standard dose of 7.4 GBq (200 mCi). (Phase Ib). 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.

Secondary Outcome Measures

Measure:Specific Aim 2
Time Frame:6 Months
Safety Issue:
Description:1. PFS (Phase Ib/II). Percentage of subjects still alive without disease getting worse or without progression (according to RECIST 5.0 Criteria).
Measure:Specific Aim 3
Time Frame:6 Months
Safety Issue:
Description:2. ORR (Phase II): Percentage of subjects still alive. Percentage of subjects who achieved a best overall response
Measure:Specific Aim 4
Time Frame:6 Months
Safety Issue:
Description:3. Demonstrate Time to Response: Time to response is defined as the time from the start of treatment until first documented evidence of PR or CR (whichever status is recorded first) (Phase Ib/II).
Measure:Specific Aim 5
Time Frame:6 Months
Safety Issue:
Description:4. Demonstrate Duration of Response: [Time Frame: From the first documented evidence of a CR or a PR until the first documented sign of disease progression or death, whichever occurred earlier (up to 180 Days).]
Measure:Specific Aim 6
Time Frame:6 Months
Safety Issue:
Description:5. OS (Phase Ib): Percentage of subjects still alive. Percentage of subjects who achieved best overall survival.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Advanced Imaging Projects, LLC

Last Updated

July 20, 2020