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

Primary Purpose

Breast Cancer

Status

Recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Inetetamab Plus Cyclophosphamide Metronomic Chemotherapy Plus AI

About this trial

This is an interventional treatment trial for Breast Cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

Voluntarily sign the informed consent form;
18-75 years old;
The expected survival period is ≥12 weeks;
Eastern Cooperative Oncology Group (ECOG) score [0-2] points;
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);
Inoperable or recurrent/metastatic breast cancer patients with aromatase inhibitor treatment failure;
In the state of disease progression before enrollment;
Measurable disease according to RECIST version 1.1 or only bone metastasis;
Adequate hematological, hepatic and renal function;
NYHA class I or II and Left ventricular ejection fraction (LVEF) ≥50%.
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);
In the state of disease progression before enrollment;
Have lesions able to and agree to perform tissue biopsy at the time requested in the study;
Treatment ≥1 line after recurrence/metastasis, or relapse within 12 months after completing trastuzumab-based adjuvant therapy or during trastuzumab adjuvant therapy;
Previously received trastuzumab for anti-HER2 therapy;
Measurable disease according to RECIST version 1.1.

Exclusion Criteria:

Allergic to the ingredients of Inetetamab, cyclophosphamide or similar drugs;
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;
Patients who cannot accept drugs orally;
Women who are pregnant or breastfeeding or planning to give birth;
Patients with currently symptomatic brain or meningeal metastasis;
History of other primary malignancy;
Resistant to steroidal or nonsteroidal aromatase Inhibitor;
Have used Inetetamab;
Patients with life-threatening, symptomatic, metastatic visceral disease.

Sites / Locations

Shusen WangRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Inetetamab Plus Cyclophosphamide Metronomic Chemotherapy Plus AI

Arm Description

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).

Outcomes

Primary Outcome Measures

Objective response rate (ORR)

The proportion of best overall response of either complete or partial response.

Secondary Outcome Measures

Clinical benefit rate (CBR)

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.

Progression free survival (PFS)

Time from the date of treatment to the date of tumor progression.

Duration of response (DOR)

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.

Overall survival (OS)

Time from the date of treatment to the date of death.

Number of Participants with Adverse Events

Number of participants with adverse events related to the treatment.

The quality of life

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.

Full Information

NCT ID

NCT04941885

First Posted

June 25, 2021

Last Updated

July 1, 2021

Sponsor

Sun Yat-sen University

1. Study Identification

Unique Protocol Identification Number

NCT04941885

Brief Title

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

Acronym

Increase

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2021

Overall Recruitment Status

Recruiting

Study Start Date

June 25, 2021 (Anticipated)

Primary Completion Date

July 1, 2023 (Anticipated)

Study Completion Date

July 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Sun Yat-sen University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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.

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

78 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Inetetamab Plus Cyclophosphamide Metronomic Chemotherapy Plus AI

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Inetetamab Plus Cyclophosphamide Metronomic Chemotherapy Plus AI

Intervention Description

Each participant receives Inetetamab plus cyclophosphamide metronomic chemotherapy plus AI.

Primary Outcome Measure Information:

Title

Objective response rate (ORR)

Description

The proportion of best overall response of either complete or partial response.

Time Frame

1 year

Secondary Outcome Measure Information:

Title

Clinical benefit rate (CBR)

Description

Time Frame

1 year

Title

Progression free survival (PFS)

Description

Time from the date of treatment to the date of tumor progression.

Time Frame

1 year

Title

Duration of response (DOR)

Description

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.

Time Frame

1 year

Title

Overall survival (OS)

Description

Time from the date of treatment to the date of death.

Time Frame

3 years

Title

Number of Participants with Adverse Events

Description

Number of participants with adverse events related to the treatment.

Time Frame

1 year

Title

The quality of life

Description

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.

Time Frame

1 year

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Voluntarily sign the informed consent form; 18-75 years old; The expected survival period is ≥12 weeks; Eastern Cooperative Oncology Group (ECOG) score [0-2] points; 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); Inoperable or recurrent/metastatic breast cancer patients with aromatase inhibitor treatment failure; In the state of disease progression before enrollment; Measurable disease according to RECIST version 1.1 or only bone metastasis; Adequate hematological, hepatic and renal function; NYHA class I or II and Left ventricular ejection fraction (LVEF) ≥50%. 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); In the state of disease progression before enrollment; Have lesions able to and agree to perform tissue biopsy at the time requested in the study; Treatment ≥1 line after recurrence/metastasis, or relapse within 12 months after completing trastuzumab-based adjuvant therapy or during trastuzumab adjuvant therapy; Previously received trastuzumab for anti-HER2 therapy; Measurable disease according to RECIST version 1.1. Exclusion Criteria: Allergic to the ingredients of Inetetamab, cyclophosphamide or similar drugs; 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; Patients who cannot accept drugs orally; Women who are pregnant or breastfeeding or planning to give birth; Patients with currently symptomatic brain or meningeal metastasis; History of other primary malignancy; Resistant to steroidal or nonsteroidal aromatase Inhibitor; Have used Inetetamab; Patients with life-threatening, symptomatic, metastatic visceral disease.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Shusen Wang, MD

Phone

+86-13926168469

wangshs@sysucc.org.cn

First Name & Middle Initial & Last Name or Official Title & Degree

Kuikui Jiang, MD

Phone

+86-15210589011

jiangkk@sysucc.org.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Shusen Wang, MD

Organizational Affiliation

Sun Yat-sen University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Shusen Wang

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510060

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Shusen Wang, MD

Phone

+86-13926168469

wangshs@sysucc.org.cn

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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