Inetetamab Plus Rapamycin and Chemotherapy for HER2+ Metastatic Breast Cancer With Abnormal Activation of PAM Pathway

NCT04736589 | Not Yet Recruiting Phase 3

• 1 other identifier: IR-1.1
• Study Type: interventional
• Target: 270
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multi-center,randomized,phase 3 clinical trial. In the study, HER2-positive metastatic breast cancer patients with abnormal activation of PI3K/Akt/mTOR pathway after progression on trastuzumab are enrolled and randomized to receive the treatment of Inetetamab plus Rapamycin plus chemotherapy or Pyrotinib plus chemotherapy.The study aimed to access the efficacy and safety of Inetetamab combined with Rapamycin and chemotherapy in HER2-positive metastatic breast cancer patients with abnormal activation of PI3K/Akt/mTOR pathway.

Conditions

Breast Cancer

Keywords

Breast Cancer; Inetetamab; Rapamycin; PI3K/Akt/mTOR pathway

Outcome Measures

Primary Outcomes (1)

• Progressive-free Survival (PFS)

  Progressive-free Survival (PFS) is defined as the time from the date of randomization to the date of first radiologically documented tumor progression or death from any cause, whichever occurs first.

  Estimated 24 months

Secondary Outcomes (4)

• Overall Response Rate (ORR)

  Estimated 24 months

• Overall Survival （OS）

  Estimated 48 months

• Clinical Benefit Rate (CBR)

  Estimated 24 months

• Safety(AEs and SAEs)

  From consent through 28 days following treatment completion

Study Arms (2)

Inetetamab plus Rapamycin plus Chemotherapy

EXPERIMENTAL

Drug: Inetetamab Initial dose of 8mg/kg, completed in 90 minutes IV infusion, and then 6 mg/kg over 30-90 minutes IV infusion every 3 weeks, until disease progression (PD) or other termination criteria are met; Drug: Rapamycin Oral 2mg, once a day; Drug: Chemotherapy drugs are not limited in this trial, please refer to their instructions for specific usage.

Drug: Inetetamab; Drug: Rapamycin; Drug: Chemotherapy

Pyrotinib plus chemotherapy

ACTIVE COMPARATOR

Drug:Pyrotinib Oral 400mg, once a day; Drug: Chemotherapy drugs are not limited in this trial, please refer to their instructions for specific usage.

Drug: Pyrotinib; Drug: Chemotherapy

Interventions

Inetetamab DRUG

Initial dose of 8mg/kg, completed in 90 minutes IV infusion, and then 6 mg/kg over 30-90 minutes IV infusion every 3 weeks.

Inetetamab plus Rapamycin plus Chemotherapy

Rapamycin DRUG

Oral 2mg, once a day.

Inetetamab plus Rapamycin plus Chemotherapy

Pyrotinib DRUG

Oral 400mg, once a day.

Pyrotinib plus chemotherapy

Chemotherapy DRUG

Chemotherapy drugs are not limited in this trial, please refer to their instructions for specific usage.

Inetetamab plus Rapamycin plus Chemotherapy; Pyrotinib plus chemotherapy

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female, Aged \> 18;
• HER2-positive breast cancer are defined as immunohistochemical (IHC) testing as +++, or IHC++ with FISH testing of positive;
• Histologically or cytologically confirmed invasive breast carcinoma with locally recurrent or radiological evidence of metastatic disease.
• Patients with HER2-positive metastatic breast cancer who have progressed disease after trastuzumab treatment include the following four types of patients (Note: The following patients are in a parallel relationship):
• Patients with HER2-positive breast cancer who have progressed during adjuvant trastuzumab treatment after surgery; or
• Patients with HER2-positive breast cancer who have relapsed or metastasized after receiving adjuvant trastuzumab therapy; or
• HER2-positive recurrent or metastatic BC patients who have progressed after receiving at least 4 weeks of trastuzumab as first-line treatment ; or
• HER2-positive metastatic BC patients who have never been treated have progressed after receiving at least 4 weeks of trastuzumab as first-line treatment.
• Genetic testing shows that the PI3K/Akt/mTOR pathway related genes are mutated;
• ECOG PS score ≤2, estimated survival time ≥6 months, and can be followed-up;
• Patients with measurable disease as per RECIST 1.1 criteria;
• Cardiopulmonary function is basically normal, LVEF≥50% within 4 weeks before starting treatment;
• An adequate liver function with the following definition:
• Total bilirubin ≤ 1.5 times the upper limit of normal value. Patients with known Gibert's disease can be included in the group if combined bilirubin ≤ 1.5 times the upper limit of normal value;
• AST and ALT ≤2.5 times the upper limit of the normal value; if there is liver metastasis, ≤5 times the upper limit of the normal value (the normal value is the normal value specified by this clinical trial center);

You may not qualify if:

• Anyone who has one of the following conditions cannot be selected for this trial:
• Participated in other clinical trials within 4 weeks;
• Have used mTOR inhibitors in the past;
• Previous use of Pyrotinib in first-line treatment stage; previous use of lapatinib is allowed;
• Accompanied by immunosuppressant or chronic corticosteroid medication, or more than 25% bone marrow radiotherapy within 4 weeks;
• Symptomatic CNS metastases or evidence of leptomeningeal disease;
• Gastrointestinal dysfunction or gastrointestinal diseases (including active ulcers);
• Hepatitis B or hepatitis C carriers, or other known chronic liver diseases; HIV positive;
• Known hypersensitivity to any study medication
• Women during pregnancy or lactation;
• Left ventricular ejection fraction \<50%; clinical manifestations of patients with obvious arrhythmia, myocardial ischemia, severe atrioventricular block, cardiac insufficiency, and severe valvular disease;
• Any malignancy within 5 years prior to randomization, with the exception of adequately treated in-situ carcinoma of the cervix uteri, basal or squamous cell carcinoma;
• The researchers decide that any other medical, social or psychological conditions which are inappropriate to participate in this trial.

Sponsors & Collaborators

• Peking Union Medical College: lead

Study Sites (1)

National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Beijing, China

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Sirolimus; pyrotinib; Drug Therapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Therapeutics

Study Officials

• Fei Ma, MD

  Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fei Ma, MD

CONTACT

86-10-87788060; drmafei@126.com

Xiuwen Guan, MD

CONTACT

86-10-87788060

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate director of the department of Medical Oncology in Cancer Hospital，Chinese Academy of Medical Sciences and Peking Union Medical College

Study Record Dates

• First Submitted: January 31, 2021
• First Posted: February 3, 2021
• Study Start: February 2, 2021
• Primary Completion: February 2, 2024
• Study Completion (Estimated): February 2, 2027
• Last Updated: February 3, 2021

Record last verified: 2021-01

Locations

CN (1)