Metastatic Breast CancerPhase 2NCT05331326
A Study of RC48-ADC for the Treatment of HER2-expression Metastatic Breast Cancer With Abnormal Activation of PAM Pathway
A Phase 2 study testing RC48-ADC in people with Metastatic Breast Cancer, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences at 3 sites in China.
Trial summary
This is a multicenter, single-arm phase II clinical trial to evaluate the efficacy and safety of RC48 in metastatic human epidermal growth factor receptor 2 (HER2) expressing breast cancer with abnormal activation of PAM pathway. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- RC48-ADC
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 3 sitesChina
- Study dates
- Apr 2022to Aug 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects aged ≥18 years (inclusive) and expected survival ≥ 12 weeks.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Histologically and/or cytologically confirmed invasive locally advanced or metastatic breast cancer that is incurable and unresectable;
- HER2 expression (positive defined as: IHC 3+ or FISH+ and low expression defined as: IHC2+and FISH- or IHC 1+); previous test results of HER2 expression provided by the subjects (have to be confirmed by the investigator) and those obtained from the study site or the central laboratory were both acceptable;
- Genetic testing shows that the PAM（PI3K/Akt/mTOR）pathway related genes are mutated; previous test results provided by the subjects (have to be confirmed by the investigator) was both acceptable.
- No more than 1 lines of chemotherapy received after relapse/metastasis. The number of chemotherapy lines is restricted to chemotherapeutic drugs, and each chemotherapy regimen is counted as a number of chemotherapy line, excluding targeted drugs and/or endocrine drugs; the same maintenance treatment as the previous chemotherapy regimen will not be counted.
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- Patients with HER2-positive metastatic breast cancer have received treatment with trastuzumab or its biosimilar (monotherapy or in combination with other drugs, such as for ≥ 3 months in the adjuvant therapy phase, and ≥ 6 weeks in the post-relapse and metastatic phase);
- With at least one measurable lesion per RECIST v1.1.
- Subjects may previously exposed to anthracyclines (e.g. doxorubicin, epirubicin) and/or taxanes (e.g., paclitaxel, docetaxel) including:
- has been pretreated in the adjuvant or neoadjuvant setting with anthracyclines and/or taxanes before breast cancer relapsing;
- has experienced treatment failure while receiving or after completing anthracycline- and/or taxane- based chemotherapy;
- not suitable for the choice of anthracycline- and/or taxane- based chemotherapy as first-line treatment in the judgment of investigator.
- Prior radiotherapy must have completed before randomization, with full recovery from acute radiation side effects. An interval of less than 4 weeks after radiotherapy was not allowed. Concurrent limited field radiation therapy (RT) is allowed. At least one measurable lesion must be completely outside the radiation portal in accordance with RECIST 1.1 guidelines.
- At least 30 days from major surgery before randomization, with full recovery.
- With Adequate Organ Function:
- Bone marrow function: Hemoglobin ≥ 10 g/dL; Absolute neutrophil count ≥ 1.5×10^9/L; Platelets ≥ 100 × 10^9/L; b .Liver function (based on the normal values specified by study site): Serum total bilirubin ≤ 1.5 × the upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN in the absence of liver metastases, while ALT, AST and ALP ≤ 5 × ULN in the presence of liver metastases; Alkaline phosphatase (ALP) ≤ 5 × ULN; c. Renal function (based on the normal values specified by study site): Creatinine clearance (CrCl) ≥40 mL/min as calculated by Cockcroft-Gault formula,
- Female patients of childbearing age have a negative pregnancy test and voluntarily take effective and reliable contraceptive measures.
- The patients voluntarily signed an informed consent form.
- Able to understand study requirements, willing and able to comply with study protocol and follow-up procedures.
Who cannot join
- History of, or current active cancer other than breast cancer, with the exception of curatively resected non-melanomatous skin cancer, curatively treated cervical carcinoma in situ, or other primary solid tumors curatively treated with no known active disease present and no curative treatment administered for the last 3 years.
- Patients with medical conditions that the only manifestation is hydrothorax, ascites, bone lesions or other un-measurable diseases.
- Subjects with symptoms suggesting central nervous system (CNS) involvement or leptomeningeal metastases, any suspicious sins or symptoms of CNS involvement or leptomeningeal metastases should be excluded by CT or MRI scans.
- Other serious illness or medical conditions by the investigator during screening:
- Clinically significant cardiac disease; Unstable diabetes; Uncontrolled hypercalcemia; Clinically significant active infections (current or in the last two weeks). With history of active tuberculosis; Patients with active hepatitis B or C (HBsAg positive and HBV DNA positive; HCVAb positive).
- Previous organ allograft.
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- Current peripheral neuropathy ≥grade 2 according to NCI version 4.0 criteria.
- Concomitant hormonal therapy for MBC.
- Ongoing anti-coagulation therapy.
- Presence of effusion in the third space (including massive hydrothorax or ascites) that cannot be controlled by drainage or other methods.
- Subjects of reproductive potential who are pregnant, breast feeding or not willing to use effective contraceptive precautions during the study and for at least one month after the last dose of investigational product in the judgment of the investigator.
- Patients with psychiatric disorder or other disease leading to incompliance to the therapy.
- An interval of less than 4 weeks between the last dose of previous chemotherapy and randomization.
- With prior treatment with T-DM1 or had participated in clinical studies with other ADCs.
- Treatment with any investigational drug within 30 days before the beginning of treatment with study drug. Less than 30 days since receipt of any other investigational product or device.
- With known hypersensitivity or delayed-type hypersensitivity to certain components of RC48-ADC.
- Subjects who are estimated to have poor compliance with the clinical study or the investigator determines that there are other factors not appropriate to participate in the study.
Trial locations and contacts
3 sites in 1 country.
Hongnan Mo contact
China3 sites, 3 recruiting
- Recruiting
Cancer Hospital, Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, 100021
Fei Ma, 86-10-87788060, drmafei@126.com
- Recruiting
Beijing Huanxing Cancer Hospital
Beijing, Beijing Municipality
Xiaoying Sun, 15910905228
- Recruiting
Cancer Hospital, Chinese Academy of Medical Sciences, Hebei Center
Langfang, Hebei
Kaiping Ou, 8615901262958
About this study
Official title: A Multicenter, Single Arm Phase II Clinical Study Evaluating the Efficacy and Safety of RC48-ADC for the Treatment of HER2-expression Metastatic Breast Cancer With Abnormal Activation of PAM Pathway
This is a multicenter, single-arm phase II clinical trial to evaluate the efficacy and safety of RC48 in metastatic human epidermal growth factor receptor 2 (HER2) expressing breast cancer with abnormal activation of PAM pathway.
Read the detailed description
A multicenter, single-arm study was conducted in 32 patients with HER2-positive breast cancer and 32 HER2-low expression patients to explore the efficacy and safety of RC48 in metastatic human epidermal growth factor receptor 2 (HER2) expressing breast cancer with abnormal activation of PAM pathway.
- Conditions
- Metastatic Breast Cancer
- Being tested
- RC48-ADC
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RC48-ADCDrug
RC48-ADC 2.0mg / kg, intravenous drip, once every 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| HER2 Positive | Experimental | Drug: RC48-ADC 2.0 mg/kg (HER2 Positive) 32 advanced breast cancer participants with HER2 Positive will be treated with RC48-ADC at a dose of 2.0mg/kg, every 2 weeks. They will continue the medication until one of the following conditions occurred: disease progression, intolerance of toxicity, withdrawal of informed consent, or treatment for 1 year. Receives: Drug: RC48-ADC |
| HER2 Low Expression | Experimental | Drug: RC48-ADC 2.0 mg/kg (HER2 Low Expression) 32 advanced breast cancer participants with HER2 Low Expression will be treated with RC48-ADC at a dose of 2.0 mg/kg, every 2 weeks. They will continue the medication until one of the following conditions occurred: disease progression, intolerance of toxicity, withdrawal of informed consent, or treatment for 1 year. Receives: Drug: RC48-ADC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate（ORR）
Objective Response Rate was defined as the percentage of participants with a complete response (CR) or partial response (PR)
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Secondary outcomes (7)
Progression Free Survival (PFS)
PFS was defined as the time from the initial date of treatment to the date of documented progression, or the date of death (in the absence of progression) of participants.
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Overall Survival(OS)
OS was defined as the time from the first study treatment to the date of death from any cause
Measured: From date of randomization until the date of death from any cause, assessed up to 48 months
Disease Control Rate (DCR)
Disease Control Rate (DCR) was defined as the percentage of patients with a complete response (CR), partial response (PR) and stable disease (SD).
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Adverse events (AEs)
The drug safety was assessed by investigator(s) according to NCI-CTCAE v5.0.
Measured: Up to 2 years
Tumor progression time (TTP)
TTP refers to the time from the random date to the first disease progression (calculated by the event that occurred first).
Measured: Up to 2 years
quality of life (QoL)
QoL measurement is conducted in the hospital after treatment via a digital questionnaire (EORTC QLQ-C30) on a tablet computer.
Measured: Up to 2 years
Change in neuropathy
As measured by change in EORTC CIPN-20 scores
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2022
- Study startApr 2022 (estimated)
- Primary completionDec 2023 (estimated)
- Study completionAug 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by Cancer Institute and Hospital, Chinese Academy of Medical SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 64 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ma Fei，MD, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
- Investigators
- Fei Ma, Principal investigator, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05331326
- Sponsor's protocol ID
- NCC3286
- Status last verified
- Apr 2022
- First submitted
- 8 Apr 2022
- Last updated
- 15 Apr 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Single Arm Phase II Clinical Study Evaluating the Efficacy and Safety of RC48-ADC for the Treatment of HER2-expression Metastatic Breast Cancer With Abnormal Activation of PAM Pathway
- ClinicalTrials.gov ID
- NCT05331326
- Acronym / sponsor ID
- NCC3286
- Conditions
- Metastatic Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 64 participants (estimated)
- Lead sponsor
- Cancer Institute and Hospital, Chinese Academy of Medical SciencesUniversity, hospital or other
- Study start
- Apr 2022 (estimated)
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Aug 2024 (estimated)
- First posted
- 15 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multicenter, single-arm phase II clinical trial to evaluate the efficacy and safety of RC48 in metastatic human epidermal growth factor receptor 2 (HER2) expressing breast cancer with abnormal activation of PAM pathway.
Detailed description
A multicenter, single-arm study was conducted in 32 patients with HER2-positive breast cancer and 32 HER2-low expression patients to explore the efficacy and safety of RC48 in metastatic human epidermal growth factor receptor 2 (HER2) expressing breast cancer with abnormal activation of PAM pathway.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HER2 Positive | Experimental | Drug: RC48-ADCDrug: RC48-ADC 2.0 mg/kg (HER2 Positive) 32 advanced breast cancer participants with HER2 Positive will be treated with RC48-ADC at a dose of 2.0mg/kg, every 2 weeks. They will continue the medication until one of the following conditions occurred: disease progression, intolerance of toxicity, withdrawal of informed consent, or treatment for 1 year. |
| HER2 Low Expression | Experimental | Drug: RC48-ADCDrug: RC48-ADC 2.0 mg/kg (HER2 Low Expression) 32 advanced breast cancer participants with HER2 Low Expression will be treated with RC48-ADC at a dose of 2.0 mg/kg, every 2 weeks. They will continue the medication until one of the following conditions occurred: disease progression, intolerance of toxicity, withdrawal of informed consent, or treatment for 1 year. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Subjects aged ≥18 years (inclusive) and expected survival ≥ 12 weeks.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Histologically and/or cytologically confirmed invasive locally advanced or metastatic breast cancer that is incurable and unresectable;
- HER2 expression (positive defined as: IHC 3+ or FISH+ and low expression defined as: IHC2+and FISH- or IHC 1+); previous test results of HER2 expression provided by the subjects (have to be confirmed by the investigator) and those obtained from the study site or the central laboratory were both acceptable;
- Genetic testing shows that the PAM（PI3K/Akt/mTOR）pathway related genes are mutated; previous test results provided by the subjects (have to be confirmed by the investigator) was both acceptable.
Key exclusion criteria (17 listed)
- History of, or current active cancer other than breast cancer, with the exception of curatively resected non-melanomatous skin cancer, curatively treated cervical carcinoma in situ, or other primary solid tumors curatively treated with no known active disease present and no curative treatment administered for the last 3 years.
- Patients with medical conditions that the only manifestation is hydrothorax, ascites, bone lesions or other un-measurable diseases.
- Subjects with symptoms suggesting central nervous system (CNS) involvement or leptomeningeal metastases, any suspicious sins or symptoms of CNS involvement or leptomeningeal metastases should be excluded by CT or MRI scans.
- Other serious illness or medical conditions by the investigator during screening:
- Clinically significant cardiac disease; Unstable diabetes; Uncontrolled hypercalcemia; Clinically significant active infections (current or in the last two weeks). With history of active tuberculosis; Patients with active hepatitis B or C (HBsAg positive and HBV DNA positive; HCVAb positive).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RC48-ADCRC48-ADC 2.0mg / kg, intravenous drip, once every 2 weeks | Drug | HER2 Low Expression, HER2 Positive |
Primary outcome
Objective Response Rate（ORR）
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Objective Response Rate was defined as the percentage of participants with a complete response (CR) or partial response (PR)
7 secondary outcomes
Progression Free Survival (PFS)
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Overall Survival(OS)
Time frame: From date of randomization until the date of death from any cause, assessed up to 48 months
Disease Control Rate (DCR)
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Adverse events (AEs)
Time frame: Up to 2 years
Tumor progression time (TTP)
Time frame: Up to 2 years
quality of life (QoL)
Time frame: Up to 2 years
Change in neuropathy
Time frame: Up to 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hongnan Mo contact
Fei Ma principal investigator
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RC48-ADC in people with Metastatic Breast Cancer, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences at 3 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Fei Ma (86-10-87788060, drmafei@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate（ORR） (time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2022.