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Inetetamab Plus Cyclophosphamide Metronomic Chemotherapy Plus Aromatase Inhibitor in Metastatic HER2+/HR+ Breast Cancer (Increase)

1. juli 2021 oppdatert av: wang shusen, Sun Yat-sen University

A Phase II Single-arm Clinical Trial of the Efficacy and Tolerability of Inetetamab Combined With Cyclophosphamide Metronomic Chemotherapy and Aromatase Inhibitor in Metastatic HER2+/HR+ Breast Cancer

Antibody-dependent cell-mediated cytotoxicity (ADCC) is one of the important mechanisms for suppressing tumors of Trastuzumab. Pre-clinical data suggest that the ADCC effect of Inetetamab, an anti-HER2 monoclonal antibody with a modified Fc segment, is 1.11 times that of trastuzumab. Previous studies indicated that enhanced ADCC effects can be transformed into clinical benefits. Immune induction through cyclophosphamide metronomic chemotherapy may further enhance the ADCC effect of anti-HER2 monoclonal antibodies. Therefore, we conducted this study to explore the efficacy and the safety of Inetetamab combined with cyclophosphamide metronomic chemotherapy and aromatase inhibitors(AI) in the treatment of metastatic HER2-positive and HR-positive breast cancer patients and to explore the possible mechanisms.

Studieoversikt

Detaljert beskrivelse

Trastuzumab is a humanized monoclonal antibody, and antibody-dependent cell-mediated cytotoxicity (ADCC) is one of its important mechanisms for suppressing tumors. Pre-clinical data suggest that the ADCC effect of Inetetamab, an anti-HER2 monoclonal antibody with a modified Fc segment, is 1.11 times that of trastuzumab. Previous studies indicated that enhanced ADCC effects can be transformed into clinical benefits, but the absolute benefits are still unsatisfactory. Further improvement of ADCC effects and monoclonal antibody-induced immune responses may improve the clinical benefits. Immune induction through cyclophosphamide metronomic chemotherapy may further enhance the ADCC effect of anti-HER2 monoclonal antibodies. According to previous clinical studies, for HR-positive and HER2-positive metastatic breast cancer patients, metronomic chemotherapy combined with endocrine therapy and anti-HER2 targeted therapy may be one of the treatment options. Therefore, we conducted this study to explore the efficacy and the safety of Inetetamab combined with cyclophosphamide metronomic chemotherapy and aromatase inhibitors(AI) in the treatment of metastatic HER2-positive and HR-positive breast cancer patients, and we further exploring the possible mechanisms.

Studietype

Intervensjonell

Registrering (Forventet)

78

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studer Kontakt Backup

Studiesteder

    • Guangdong
      • Guangzhou, Guangdong, Kina, 510060
        • Rekruttering
        • Shusen Wang
        • Ta kontakt med:

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år til 75 år (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Hunn

Beskrivelse

Inclusion Criteria:

  1. Voluntarily sign the informed consent form;
  2. 18-75 years old;
  3. The expected survival period is ≥12 weeks;
  4. Eastern Cooperative Oncology Group (ECOG) score [0-2] points;
  5. The diagnosis of invasive carcinoma by histology or cytology; Estrogen receptor (ER) positive (defined as >1% nuclear ER staining); HER2 negative (defined as IHC 0 or 1+, or HER2(2+) with HER2 FISH detection no amplification);
  6. Inoperable or recurrent/metastatic breast cancer patients with aromatase inhibitor treatment failure;
  7. In the state of disease progression before enrollment;
  8. Measurable disease according to RECIST version 1.1 or only bone metastasis;
  9. Adequate hematological, hepatic and renal function;
  10. NYHA class I or II and Left ventricular ejection fraction (LVEF) ≥50%.
  11. The diagnosis of invasive carcinoma by histology or cytology: Hormone receptor (HR) positive (defined as >1% nuclear estrogen receptor staining); HER2 positive (defined as IHC 3+, or HER2 FISH detection amplification);
  12. In the state of disease progression before enrollment;
  13. Have lesions able to and agree to perform tissue biopsy at the time requested in the study;
  14. Treatment ≥1 line after recurrence/metastasis, or relapse within 12 months after completing trastuzumab-based adjuvant therapy or during trastuzumab adjuvant therapy;
  15. Previously received trastuzumab for anti-HER2 therapy;
  16. Measurable disease according to RECIST version 1.1.

Exclusion Criteria:

  1. Allergic to the ingredients of Inetetamab, cyclophosphamide or similar drugs;
  2. Concomitant diseases/conditions that is not controllable, and any other major illness that, in the investigator's judgment, will substantially increase the risk associated with the patient's participation in this study;
  3. Patients who cannot accept drugs orally;
  4. Women who are pregnant or breastfeeding or planning to give birth;
  5. Patients with currently symptomatic brain or meningeal metastasis;
  6. History of other primary malignancy;
  7. Resistant to steroidal or nonsteroidal aromatase Inhibitor;
  8. Have used Inetetamab;
  9. Patients with life-threatening, symptomatic, metastatic visceral disease.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Inetetamab Plus Cyclophosphamide Metronomic Chemotherapy Plus AI
Each participant receives Inetetamab(8mg/kg iv day 1 followed by 6mg/kg iv day 1, cycled every 21 days) plus cyclophosphamide metronomic chemotherapy(50mg once a day orally) plus aromatase(once a day orally).
Each participant receives Inetetamab plus cyclophosphamide metronomic chemotherapy plus AI.

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Objektiv responsrate (ORR)
Tidsramme: 1 år
Andelen beste totalrespons av enten fullstendig eller delvis respons.
1 år

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Clinical benefit rate (CBR)
Tidsramme: 1 year
Response and progression will be evaluated using RECIST 1.1. Evaluation will occur every 3 months till progression or termination of the study. CBR is defined as ratio of participants who have stable disease for over 24 weeks.
1 year
Progression free survival (PFS)
Tidsramme: 1 year
Time from the date of treatment to the date of tumor progression.
1 year
Duration of response (DOR)
Tidsramme: 1 year
Time from the first assessment of the tumor as complete or partial response to the first assessment as PD (Progressive Disease) or death from any cause.
1 year
Total overlevelse (OS)
Tidsramme: 3 år
Tid fra behandlingsdato til dødsdato.
3 år
Antall deltakere med uønskede hendelser
Tidsramme: 1 år
Antall deltakere med uønskede hendelser knyttet til behandlingen.
1 år
The quality of life
Tidsramme: 1 year
Using Functional Assessment of Cancer therapy -Breast (FACT-B) scale. The minimum and maximum values are 0 and 144, respectively. Higher scores mean better outcome.
1 year

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Etterforskere

  • Hovedetterforsker: Shusen Wang, MD, Sun Yat-sen University

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Forventet)

25. juni 2021

Primær fullføring (Forventet)

1. juli 2023

Studiet fullført (Forventet)

1. juli 2025

Datoer for studieregistrering

Først innsendt

25. juni 2021

Først innsendt som oppfylte QC-kriteriene

25. juni 2021

Først lagt ut (Faktiske)

28. juni 2021

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

2. juli 2021

Siste oppdatering sendt inn som oppfylte QC-kriteriene

1. juli 2021

Sist bekreftet

1. juli 2021

Mer informasjon

Begreper knyttet til denne studien

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

NEI

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Nei

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

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