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HER2-negative Breast CancerPhase 2NCT04848454

Efficacy and Safety of Combinition of Camrelizumab in Second-line Neoadjuvant Chemotherapy and Adjuvant Therapy

A Phase 2 study testing Camrelizumab with vinorelbine and cisplatin in people with HER2-negative Breast Cancer and Neoadjuvant Therapy, run by Peking University First Hospital at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The achievement of pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) is associated with improved outcome across all breast cancer (BC) subtypes. Anthracycline and taxanes based chemotherapy is usually the first choice of NACT for human epidermal growth factor receptor 2 (HER2) negative breast… Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
Camrelizumab with vinorelbine and cisplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteChina
Study dates
20 Nov 2021to 31 Dec 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 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Be willing and able to join the trial and the follow-up; provide written informed consent.
  • Be a male or female subject at the age when signing the informed consent of 18-70 years old.
  • Have invasive breast cancer confirmed by histopathology, HER2 negative and suitable for neoadjuvant therapy (clinical stage is II or III).
  • With at least one mearsurable lesions according to RECIST 1.1 criteria.
  • No significant early response to first-line neoadjuvant therapy with anthracyclines and taxanes. Definition: first-line neoadjuvant regimen mainly refers to regimen: intravenous infusion of epirubicin 75mg/m2 day 1 or pirarubicin 60mg/m2 day 1 or liposome doxorubicin 25-35mg/m2 day 1, docetaxel 75mg/m2 day 2 or paclitaxel 135-175mg/m2 day 2 or albumin paclitaxel 200-260mg/m2 day 2, once every 3 weeks. After 2 cycles of treatment, the tumor size did not reach partial response (defined as the sum of the target lesion diameter decreased by at least 30% compared with the baseline), and second-line neoadjuvant therapy was considered.
  • Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Have an estimated life expectancy more than 6 months.
  • Have adequate organ function, including: ① Bone marrow reserve (not using any blood components or cell growth factors within 14 days): WBC≥4.0×10^9/L, NEUT ≥ 1.5×10^9/L, PLT≥100×10^9/L, HGB≥100g/L; ② Hepatic function: ALT, AST≤2.5 ULN, total bilirubin≤ 1.5ULN; ③Renal function: Serum Creatinine≤1.5 ULN or creatinine clearance rate ≥50ml/min (Cockcroft Gault formula); ④ Has normal cardiac function as evidenced by an left ventricular ejection fraction (LVEF) ≥50% by echocardiogram. No obvious abnormal case in electrocardiogram. ⑤Female subjects of child-bearing age must carry out serum pregnancy test within 3 days before starting the study treatment, and the result must be negative, and they have to use a highly effective contraceptive measure (such as intrauterine device, contraceptive or condom) approved by medicine during the study period and within 3 months after the last administration of the study drug; for male subjects with female partners of child-bearing age, they should agree to use the contraceptive measure during the study period and within 3 months after the last study drug treatment .

Who cannot join

  • Has any evidence of metastatic disease.
  • Has received chemotherapy, targeted therapy, endocrine therapy or local radiotherapy in the past.
  • Previously received anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody or anti-CTLA-4 antibody (or any other antibody acting on T cell costimulation or checkpoint pathway).
  • A clear history of allergy may lead to potential allergy or intolerance to the study drug and its similar biological agents.
  • Participated in clinical trials of other anti-tumor drugs within 4 weeks before the first administration; or received live attenuated vaccine within 4 weeks before the first administration or planned during the study period.
  • Had other malignant tumors occurred within 5 years (except for completely treated squamous cell carcinoma of skin or controlled basal cell carcinoma of skin).
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  • Immunosuppressive drugs were used within 14 days before the first use of camrelizumab, excluding nasal and inhaled corticosteroids or physiological doses of systemic steroids (i.e. not more than 10 mg/day of prednisolone or other corticosteroids of the same pharmacophysiological dose).
  • Active autoimmune disease or history of autoimmune disease: including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism; subjects with vitiligo or asthma in childhood had complete remission and did not need any intervention in adulthood could be included; asthma that needs bronchodilator for medical intervention cannot be included.
  • Grade II or above myocardial ischemia or myocardial infarction, poorly controlled arrhythmia (including QTc interval ≥450ms in male and ≥470ms in female); NYHA grade III-IV heart failure, or left ventricular ejection fraction (LVEF) < 50% by echocardiography; myocardial infarction within 6 months; NYHA grade I-II, uncontrolled angina pectoris, uncontrolled severe ventricular arrhythmia, clinically significant pericardial disease; ECG showed acute ischemia or active abnormality of conduction system.
  • Severe infection occurred within 4 weeks before the first administration (e.g. intravenous drip of antibiotics, antifungal or antiviral drugs) or fever of unknown origin > 38.5 ℃ occurred during the screening period or before the first administration.
  • History of psychotropic substance abuse and can not give up or have mental disorders.
  • Major surgery performed within 4 weeks before the first administration; with open wound or fracture;
  • The adverse reactions related to anti-tumor therapy (except alopecia) did not return to nci-ctcae ≤ 1 after first-line neoadjuvant therapy.
  • Other circumstances judged by the researchers not suitable for participation in this study.

Trial locations and contacts

1 site in 1 country.

China1 site, 1 recruiting
  • Peking University First Hospital

    Beijing, Beijing Municipality, 100034

    Ling Xu, M.D., 13651344156, xuling_en@126.com

    Recruiting

Other trials in China

About this study

Official title: Neoadjuvant Camrelizumab Combined to Vinorelbine and Cisplatin as Second Regimen to Non-optimal Response to Taxanes and Anthracyclines on Patients With Early Stage HER2-negative Breast Cancer: A Single Arm Phase 2 Trial

The achievement of pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) is associated with improved outcome across all breast cancer (BC) subtypes. Anthracycline and taxanes based chemotherapy is usually the first choice of NACT for human epidermal growth factor receptor 2 (HER2) negative breast cancer, but there is no ideal second-line therapy for those with unsatisfactory effect after first-line NACT. Vinorelbine combined with cisplatin may be a choice for patients after failure or progression with anthracycline and/or taxanes. Immunotherapy has achieved good efficacy in many malignant tumors. Chemotherapy may have a certain immune activation effect, thus combination of immunotherapy and chemotherapy has significant clinical value in neoadjuvant and adjuvant treatment of breast cancer.

So we designed this one center single arm phase 2 clinical trial to test the efficacy and safety of camrelizumab (PD-1 inhibitor) combined with vinorelbine and cisplatin as a second-line therapy for HER2 negative breast cancer patients who did not achieve significant effect after 2 cycle treatments of anthracycline plus taxanes NACT.

The target population of our study are early-stage HER2 negative breast cancer patients with indications of NACT who did not receive partial response after 2 cycle of standard anthracycline and taxanes treaments according to RECIST 1.1 criteria. The enrolled patients will receive 6 cycles of camrelizumab combined with vinorelbine and cisplatin as second-line neoadjuvant therapy. Then they need to undergo surgery. The subjects have to continue camrelizumab until it is totally used for 1 year (about 17 cycles in all). The patients will routinely receive conventional adjuvant therapy and enter the long-term follow-up to get their survival infoumation.

Read the detailed description

It has been proved that the achievement of pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) is associated with improved outcome across all breast cancer (BC) subtypes. At present, anthracycline and taxanes based chemotherapy is usually the first choice of neoadjuvant therapy for human epidermal growth factor receptor 2 (HER2) negative breast cancer, and the response rate can be more than 2/3. However, there are still some patients not getting satisfactory outcome using this regimen, for whom there is no unified ideal second-line neoadjuvant therapy to choose. Studies on metastatic BC have shown that vinorelbine combined with cisplatin has good efficacy and safety in the treatment of patients after failure or progression with anthracycline and/or taxanes. In other studies, patients with poor response to anthracycline and taxanes based NACT changed to NACT containing vinorelbine could obtain improved long-term survival. These results suggest that adjusting the neoadjuvant therapy according to the efficacy may bring more benefits to patients and vinorelbine combined with cisplatin is one of the second-line options for HER2 negative breast cancer who has been treated by the anthracycline and taxanes based NACT but not getting good efficacy.

Immunotherapy has achieved good efficacy in many malignant tumors. The US Food and Drug Administration (FDA) has approved the indications for the use of pembrolizumab ( an anti-PD-1 antibody) and atezolizumab (an anti -PD-L1 antibody) in patients with unresectable locally advanced or metastatic triple negative breast cancer. In neoadjuvant therapy, many studies have shown that the increase of pCR rate after NACT combined with immunotherapy, and the clinical benefit is obvious in the early stage. This was hypothesized that chemotherapy including anthracyclines or other drugs may have a certain immune activation effect, thus combination of immunotherapy and chemotherapy has significant clinical value in neoadjuvant and adjuvant treatment of breast cancer.

Based on the above background, we propose the hypothesis that camrelizumab combined with vinorelbine and cisplatin can be recommended for HER2 negative breast cancer patients who did not achieve significant efficacy after 2 cycle treatments of anthracycline plus taxanes as first-line neoadjuvant therapy. In order to confirm this hypothesis, we designed the following one centre single arm phase 2 clinical trial.

We defined the target population of our study as those early-stage HER2 negative breast cancer (triple negative breast cancer and HER2 negative hormone receptor positive breast cancer) patients with indications of NACT who did not receive partial response after 2 cycle of standard anthracycline and taxanes treaments according to RECIST 1.1 criteria. We expect to recruit 30 subjects. The enrolled patients will receive 6 cycles of neoadjuvant therapy of camrelizumab combined with vinorelbine and cisplatin (NP) as second-line neoadjuvant therapy. After the patients complete the neoadjuvant therapy or stop treatment due to disease progression, intolerance of adverse reactions or other conditions that the researchers thought they could not continue to benefit from the treatment, they need to undergo surgery in 4 weeks. The subjects have to continue camrelizumab every 3 weeks like during the preoperative phase until it is totally used for 1 year (about 17 cycles in all). In addition, the patients will routinely receive conventional treatment, endocrine therapy and other adjuvant therapy. Our primary objection is to evaluate the efficacy of second-line neoadjuvant therapy with camrelizumab combined with NP; and the secondary objection is to verify this regimen's security. The efficacy of camrelizumab and NP neoadjuvant therapy will be evaluated according to the assessment during treatment, postoperative pathological results and follow-up results. We will record the clinical response, pCR, progression-free survival and overall survival etc. Safety information will be collected continuously at the beginning of study treatment until the completion of follow-up after study treatment. Besides, we will do some exploratory research using the histological or blood samples of the subjects about biomarkers (like tumor infiltrating lymphocytes, expression of PD-L1 etc.) that may be used for clinical prediction, selection of suitable population and other situations.

Being tested
Camrelizumab with vinorelbine and cisplatin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Camrelizumab with vinorelbine and cisplatinDrug

    Camrelizumab: 200mg iv., every 3 weeks(one cycle), for 1 year(17cycles in total); Vinorelbine: 25mg/m2 day 1, 8 iv. or 60-80 mg/m2 or. day1, 8, every 3 weeks(one cycle), for 6 cycles; Cisplatin: 75mg/m2 (divided into 2 days), every 3 weeks(onr cycle), for 6 cycles.

Study groups in NCT04848454
Study groupRoleWhat they receive
Experimental groupExperimentalDrug: Vinorelbine i.v. 25 mg/m2, d1, d8 or p.o. 60-80 mg/m2 d1, d8; q3w; for 6 cycles. Cisplatin i.v. 75 mg/m2,d1, d2; q3w; for 6 cycles. Camrelizumab i.v. 200mg, q3w; for 17cycles (1 year).
Receives: Drug: Camrelizumab with vinorelbine and cisplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pathological complete response (pCR)

    The rate of pCR use the definition of ypT0/Tis ypN0 (i.e., no invasive residual in breast or nodes; noninvasive breast residuals allowed) as assessed by the local pathologist at the time of definitive surgery.

    Measured: 1 month after the definitive surgery (if the patient does receive the surgery, usually 3-4 weeks after the last cycle of neoajuvant therapy)

Secondary outcomes (3)
  1. Objective response rate (ORR)

    The rate of patients with complete remission (CR) or partial response (PR) evaluated by RECIST 1.1 criteria by site radiology review before operation.

    Measured: 1 month after the last cycle of neoadjuvant therapy

  2. Event-free survival (EFS) rate

    The rate of patients in all assessable subjects without any of the following events: progression of disease that precludes surgery, local or distant recurrence (surgical complete resection of local lesion) , second primary malignancy (breast or other cancers) or death due to any cause.

    Measured: 5 years

  3. Breast-conserving surgery rate

    The rate of assessable patients undergoing breast-conserving surgery.

    Measured: During the definitive surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Apr 2021
  2. Study start20 Nov 2021
  3. Primary completion28 Feb 2024 (estimated)
  4. Study completion31 Dec 2024 (estimated)

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04848454
Sponsor's protocol ID
OBU-BJ-BB-BC-II-007
Status last verified
Oct 2022
First submitted
8 Apr 2021
Last updated
18 Oct 2022
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Camrelizumab with vinorelbine and cisplatin in people with HER2-negative Breast Cancer and Neoadjuvant Therapy, run by Peking University First Hospital at 1 site 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 8 inclusion and 14 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 18 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 Ling Xu, M.D. (+86-010-83575053, xuling_en@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathological complete response (pCR) (time frame: 1 month after the definitive surgery (if the patient does receive the surgery, usually 3-4 weeks after the last cycle of neoajuvant therapy)). 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 18 Oct 2022.

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