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

NCT04848454 | Unknown Phase 2

• 1 other identifier: OBU-BJ-BB-BC-II-007
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

HER2-negative Breast Cancer; Neoadjuvant Therapy; Pathological Complete Response; Immunotherapy; Vinorelbine; Cisplatin

Outcome Measures

Primary Outcomes (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.

  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)

• Objective response rate (ORR)

  1 month after the last cycle of neoadjuvant therapy

• Event-free survival (EFS) rate

  5 years

• Breast-conserving surgery rate

  During the definitive surgery

Study Arms (1)

Experimental group

EXPERIMENTAL

Drug: 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).

Drug: Camrelizumab with vinorelbine and cisplatin

Interventions

Camrelizumab with vinorelbine and cisplatin DRUG

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.

Experimental group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 .

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Peking University First Hospital: lead

Study Sites (1)

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

RECRUITING

MeSH Terms

Interventions

camrelizumab; Vinorelbine; Cisplatin

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Central Study Contacts

Ling Xu, M.D.

CONTACT

+86-010-83575053; xuling_en@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician of Breast Disease Center, Associate Professor, M.D.

Study Record Dates

• First Submitted: April 8, 2021
• First Posted: April 19, 2021
• Study Start: November 20, 2021
• Primary Completion: February 28, 2024
• Study Completion: December 31, 2024
• Last Updated: October 18, 2022

Record last verified: 2022-10

Locations

CN (1)