Dynamic Observational Study With PET of 68Ga-HER2-affibody in Anti-HER2 Treatment

A Phase II, Single-center, Dynamic Observational Study With PET of 68Ga-HER2-affibody in Anti-HER2 Treatment

Dynamic observationaL study with PET of 68Ga-HER2-affibody in anti-HER2 treatment

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Docetaxel combined with Trastuzumab±Pertuzumab; Drug: T-DM1 or Capecitabine combined with Pyrotinib regimen.

Detailed Description

Participants participated in the screening period visit, and received HER2-PET and 18 F-FDG PET/CT examinations before receiving tumor treatment, after receiving 2 cycles of chemotherapy, and after disease progression. Patients of first-line received docetaxel combined with trastuzumab±pertuzumab regimen, and patients of second-line received T-DM1 monotherapy or capecitabine combined with pyrrotinib regimen.

• Study Type: Observational
• Enrollment (Anticipated): 50

Contacts and Locations

• Study Contact: Name: Xichun Hu, MD, PhD; Phone Number: 5006 64175590; Email: huxicun@gmail.com
• Study Contact Backup: Name: Jian Zhang, M.D.; Phone Number: 85000 64175590; Email: syner2000@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Xichun Hu, MD, PhD; Phone Number: 5006 64175590; Email: huxicun@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Patients with HER2 positive recurrent or metastatic breast cancer

Description

Inclusion Criteria:

1. Subjects voluntarily joined the study, signed informed consent, and had good compliance.
2. Female patients aged over 18 years (including cutoff value).
3. an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
4. Patients with HER2 positive recurrent or metastatic breast cancer confirmed by histopathology.
5. At least one extracranial measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1.
6. Previously received no more than 1 prior lines of systemic chemotherapy for metastatic breast cancer
7. Life expectancy ≥ 12 weeks.

8. Adequate function of major organs meets the following requirements (no blood components and cell growth factors have been used within 14 days before randomization):

   • Neutrophils ≥ 1.5×10^9/L
   • Platelets ≥ 75×10^9/L
   • Hemoglobin ≥ 80g/L
   • Total bilirubin≤ 1.5 × the upper limit of normal (ULN)
   • ALT and AST ≤ 3 × ULN
   • BUN and Cr ≤ 1.5 × ULN
   • Left ventricular ejection fraction (LVEF) ≥ 50%
   • QTcF(Fridericia correction) ≤ 470 ms

Exclusion Criteria:

1. The subject has untreated central nervous system (CNS) metastases.
2. Patients who have undergone systemic, radical brain or meningeal metastasis (radiotherapy or surgery), but have been confirmed to have been stable for at least 4 weeks, and who have stopped systemic hormonal therapy for more than 2 weeks without clinical symptoms can be included.
3. Received systemic therapy such as chemotherapy, molecular targeted therapyment;received endocrine therapy within 2 weeks before enrollment.
4. Patients with other malignant tumors within 3 years or at the sametime(except for cured skin basal cell carcinoma and cervical carcinomain situ).
5. Have undergone major surgical procedures or significant trauma within 4 weeks prior to randomization, or are expected to undergo major surgery.
6. Pregnant women, lactating female, or women of childbearing age who are unwilling to take effective contraceptive measures.
7. Have a history of allergies to the drug components of this regimen.
8. Patients with active HBV and HCV infection; stable hepatitis B after drug treatment (HBV virus copy number is higher than the upper limit of reference value) and cured hepatitis C patients (HCV virus copy number exceeds the lower limit of detection method).
9. History of immunodeficiency, including HIV positive, or other acquired or congenital immunodeficiency disease, history of organ transplantation.
10. History of cardiac dysfunction, include(1)angina (2)clinical significant arrythmia or require drug intervention (3)myocardial infarction (4)heart failure (5) other cardiac dysfunction (judged by the physician); any cardiac or nephric abnormal ≥ grade 2 found in screening.
11. Female patients who are pregnancy, lactation or women who are ofchildbearing potential tested positive in baseline pregnancy test.
12. Childbearing female who refuse to accept any contraception practice.
13. Determined by the physician, any serious coexisting disease might be harmful to the patient's safety or avoid the patients from accomplishing the treatment(e.g serious hypertension, diabetes, thyroid dysfunction,active infection etc.).
14. History of neurological or psychiatric disorders, including epilepsy or dementia.
15. Severe infections within 4 weeks prior to first dose (eg, intravenous infusion of antibiotics, antifungal or antiviral drugs according to clinical protocols), or unexplained fever (T > 38.3 °C ) during screening or prior to first administration

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
First-line patients; First-line treatment of HER2-positive metastatic breast cancer patients	Drug: Docetaxel combined with Trastuzumab±Pertuzumab; Docetaxel, 75 mg/m2 ivgtt d1 q3w Trastuzumab, 6 mg/kg(8 mg/kg for initial dose) ivgtt d1 q3w Pertuzumab, 420mg(840mg for initial dose) ivgtt d1 q3w
Second-line patients; Second-line treatment of HER2-positive metastatic breast cancer patients	Drug: T-DM1 or Capecitabine combined with Pyrotinib regimen.; T-DM1, 3.6mg/kg(8 mg/kg for initial dose) ivgtt d1 q3w Capecitabine, 1250 mg/m2 bid po d1-14 q3w Pyrotinib, 400mg po daily (continuously)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The correlation between the change of HER2-PET at baseline and after 2 courses of treatment and ORR.	The correlation between the percent change in standardized uptake value (SUV) on 68Ga-Affibody HER-2 Imaging PET at baseline and after 2 courses of treatment and objective response rate(ORR).	2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The correlation between the change of HER2-PET at baseline and after 2 courses of treatment and PFS	The correlation between the percent change in SUV on 68Ga-Affibody HER-2 Imaging PET at baseline and after 2 courses of treatment and progression-free survival(PFS).	2 year
The correlation between baseline HER2 expression and ORR, PFS	The correlation between the baseline SUVmax on 68Ga-Affibody HER-2 Imaging PET and ORR, PFS.	2 year
The correlation between heterogeneity of baseline HER2 expression and ORR, PFS	The correlation between heterogeneity of the baseline SUVmax on 68Ga-Affibody HER-2 Imaging PET and ORR, PFS.	2 year
To explore the condition of HER2-PET when PD.	To detection the change in SUVmax on 68Ga-Affibody HER-2 Imaging PET when progressive disease(PD).	2 year

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2021
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: February 15, 2021
• First Submitted That Met QC Criteria: February 23, 2021
• First Posted (Actual): February 24, 2021

Study Record Updates

• Last Update Posted (Actual): April 20, 2022
• Last Update Submitted That Met QC Criteria: April 19, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Immunological; Docetaxel; Trastuzumab; Capecitabine; Pertuzumab
• Other Study ID Numbers: Dolphin

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