Trial Title:
The Efficacy and Safety of Lenvatinib Combined With Sindilimab and Nab-paclitaxel in the First-line Treatment for Recurrent and Metastatic Triple Negative Breast Cancer: a Phase Ib/IIa Clinical Trial.
NCT ID:
NCT06140576
Condition:
Breast Neoplasms
Conditions: Official terms:
Triple Negative Breast Neoplasms
Breast Neoplasms
Paclitaxel
Lenvatinib
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Lenvatinib combined with Sindilimab and Nab-paclitaxel in the first-line treatment for
recurrent and metastatic triple negative breast cancer.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Sindilimab
Description:
Sindilimab, 200mg, Intravenous，every three weeks
Arm group label:
Lenvatinib combined with Sindilimab and Nab-paclitaxel
Intervention type:
Drug
Intervention name:
Nab-paclitaxel
Description:
Nab-paclitaxel，125mg/m^2, d1,8, every three weeks
Arm group label:
Lenvatinib combined with Sindilimab and Nab-paclitaxel
Intervention type:
Drug
Intervention name:
Lenvatinib
Description:
Lenvatinib 8mg, 12mg, 16mg everyday
Arm group label:
Lenvatinib combined with Sindilimab and Nab-paclitaxel
Summary:
The treatment regimen of lenvatinib combined with PD1 antibody has brought earth shaking
changes to the immunotherapy of various "cold tumors". This is a phase Ib/IIa clinical
trial to investigate the efficacy and safety of Lenvatinib combined with Sindilimab and
Nab-paclitaxel in the first-line treatment for recurrent and metastatic triple negative
breast cancer.
Detailed description:
In recent years, the research on immunotherapy in triple negative breast cancer has been
carried out in full swing, but the results are inconsistent. Lenvatinib is an oral multi
kinase inhibitor with main targets including VEGFR1-3, FGFR1-4, and PDGFR-α, KIT and RET.
It inhibits the FGFR4 signaling pathway, and downregulate the expression of PD-L1 in
tumor cells, thereby regulating the tumor immune microenvironment. The treatment regimen
of lenvatinib combined with PD1 antibody has brought earth shaking changes to the
immunotherapy of various "cold tumors". This is a phase Ib/IIa clinical trial to
investigate the efficacy and safety of Lenvatinib combined with Sindilimab and
Nab-paclitaxel in the first-line treatment for recurrent and metastatic triple negative
breast cancer.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Breast cancer patients aged ≥ 18 years and ≤ 70 years.
2. According to the definition of the latest ASCO/CAP guidelines, recurrent metastatic
triple negative invasive breast cancer confirmed by histopathology meets the
following conditions according to recent and previous pathological results: HER2
negative: IHC 0/1+or IHC2+but ISH is negative; ER negative: IHC<1%, PR negative:
IHC<1%.
3. Patients who have received (new) adjuvant chemotherapy need to make progress at
least 6 months after the end of the last adjuvant chemotherapy.
4. ECOG score 0-1.
5. In the stage of recurrence and metastasis, without receiving systematic anti-tumor
treatment;
6. According to RECIST 1.1 standard, at least one measurable lesion exists.
7. The expected survival period is not less than 3 months.
8. The functional level of organs must meet the following requirements:
Blood routine Neutrophil count (ANC) ≥ 1.5 × 10^9/L (no hematopoietic stimulating
factor drugs were used within 14 days before the first administration of the study);
Platelet count (PLT) ≥ 100 × 10^9/L (no blood transfusion within 14 days before the
first administration of the study); Hemoglobin (Hb) ≥ 90 g/L; Blood biochemistry
Total bilirubin (TBIL) ≤ 1.5 × ULN; Glutathione aminotransferase and alanine
aminotransferase (ALT and AST) ≤ 2.5 × ULN; Blood urea nitrogen (BUN) and creatinine
clearance rate (Cr) ≤ 1.5 × ULN; Thyroid stimulating hormone (TSH) ≤ upper limit of
normal value (ULN); If there are abnormalities, the levels of T3 and T4 should be
examined. If the levels of T3 and T4 are normal, they can be selected; Cardiac
function Left ventricular ejection fraction ≥ 50% and 12 lead electrocardiogram:
QTcF<480ms.
9. Women of childbearing age must undergo a serum pregnancy test within 7 days before
enrollment, with a negative result, and are willing to use a medically recognized
and efficient contraceptive method during the study period and within 3 months after
the last administration of the study medication.
10. The subjects voluntarily joined this study and signed an informed consent form.
Exclusion Criteria:
1. Tumor related symptoms and treatment
1. Active or symptomatic brain metastasis There are metastases in the midbrain,
pons, medulla oblongata, or spinal cord. Meningeal metastasis; Symptoms related
to the nervous system, such as increased intracranial pressure and abnormal
neurological function; Received surgical treatment within 28 days of
enrollment, received whole brain radiotherapy within 14 days, or received
stereotactic radiotherapy within 7 days; If the patient only has supratentorial
and/or cerebellar metastases and has undergone local treatment
(surgery/radiotherapy for all known lesions), clinical stability is at least 2
weeks after completion of treatment, imaging shows no disease progression or
bleeding, and does not need to receive hormone treatment or receive ≤ 10mg/day
of prednisone or equivalent dose hormone treatment within 14 days of initial
administration, patients can participate in the study.
2. Uncontrolled moderate to large amounts of pleural effusion, intraperitoneal
effusion, or pericardial effusion that require repeated drainage;
3. Within 14 days prior to enrollment, receive systematic anti-tumor therapy
(including chemotherapy, radiotherapy, immunotherapy, endocrine therapy,
targeted therapy, biotherapy, or tumor embolization);
4. Imaging examination shows that the tumor invades large blood vessels, or
researchers determine that the tumor is highly likely to invade important blood
vessels and cause fatal massive bleeding during subsequent studies;
5. Subjects with uncontrollable or symptomatic hypercalcemia (>1.5mmol/L ionic
calcium concentration or>12mg/dL serum calcium concentration or serum calcium
(albumin corrected) concentration>ULN); Symptomatic hypercalcemia that may
require further bisphosphate treatment;
6. Previously received treatment with PD-1/PD-L1 antibodies, CTLA-4 antibodies, or
other anti angiogenic drugs (including monoclonal antibodies, TKI) targeting
PD-1/PD-L1;
2. Combined diseases/medical history
1. Having previously received any systematic anti-tumor treatment or local
treatment (including surgery and radiation therapy) for other malignant tumors,
excluding various cured malignant tumors such as in situ cancer, cervical
cancer, basal cell carcinoma or squamous cell carcinoma, thyroid cancer, etc;
2. The patient has undergone major surgical procedures unrelated to breast cancer
within 4 weeks before enrollment, or has not fully recovered from such surgical
procedures (tissue biopsy and central venous catheter placement via peripheral
vein puncture required for diagnosis are allowed);
3. Subjects with any known or suspected autoimmune diseases, except for those who
only require hormone replacement therapy for hypothyroidism caused by
autoimmune thyroiditis; Subjects with stable type I diabetes whose blood sugar
is controlled;
4. Interstitial lung disease, non infectious pneumonia or uncontrollable systemic
diseases (such as diabetes, pulmonary fibrosis and acute pneumonia);
5. A history of receiving live or attenuated vaccines within 28 days prior to the
first study medication, or an estimated period of receiving live or attenuated
vaccines during the study period;
6. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency
syndrome (AIDS); Active hepatitis (hepatitis B, defined as HBV-DNA ≥ 30
copies/ml; hepatitis C, defined as HCV-RNA higher than the detection limit of
the analytical method) or co infection of hepatitis B and hepatitis C;
Autoimmune hepatitis;
7. Severe infections, including but not limited to bacteremia, severe pneumonia,
etc. that require hospitalization treatment, exist within 4 weeks before the
first administration; Or there is an active infection of CTCAE ≥ 2 level that
requires systemic antibiotic treatment within 2 weeks before the first
administration, or an unexplained fever>38.5 ° C during the screening
period/before the first administration (according to the researcher's judgment,
fever caused by tumor can be included); There is evidence of active
tuberculosis infection within one year before administration;
8. Subjects who have previously received or are preparing to receive allogeneic
bone marrow transplantation or solid organ transplantation;
9. Peripheral neuropathy ≥ level 2;
10. Serious heart disease or discomfort, including but not limited to the following
diseases:
Confirmed history of heart failure or systolic dysfunction (LVEF<50%) High risk
uncontrolled arrhythmias, such as atrial tachycardia, resting heart rate>100 bpm,
significant ventricular arrhythmias (such as ventricular tachycardia), or
higher-level atrioventricular block (such as Mobitz II second degree
atrioventricular block or third degree atrioventricular block) Angina pectoris
requiring treatment with anti angina drugs Clinically significant heart valve
disease Electrocardiogram shows transmural myocardial infarction Poor control of
hypertension (systolic blood pressure>180 mmHg and/or diastolic blood pressure>100
mmHg)
3. Research and treatment related
1. Subjects who have received systemic immunostimulatory therapy (including but
not limited to interferon or interleukin-2, including immunostimulators in
clinical research) within 4 weeks prior to the first administration;
2. Subjects who have received systemic immunosuppressive therapy (including but
not limited to glucocorticoids, azathioprine, methotrexate, thalidomide, and
anti-tumor factor drugs) within 2 weeks before the first administration.
Excluding systemic corticosteroids with nasal spray and inhaled corticosteroids
or physiological doses (i.e. other corticosteroids with physiological doses not
exceeding 10mg/d prednisone or equivalent);
3. Known allergies to the study drug or any of its excipients; Or have experienced
severe allergic reactions to other monoclonal antibodies;
4. Pregnant and lactating female patients, those with fertility and positive baseline
pregnancy test results, or those of childbearing age who are unwilling to take
effective contraceptive measures throughout the entire trial period.
5. Have a clear history of neurological or mental disorders, including epilepsy or
dementia, and the subject is known to have a history of abuse of psychotropic
substances, alcohol or drug use;
6. The researcher believes that the patient is not suitable to participate in any other
situation of this study.
Gender:
Female
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
ZhejiangCH
Address:
City:
Hangzhou
Country:
China
Contact:
Last name:
Ying Xi Shao
Investigator:
Last name:
Jia Xiao Wang
Email:
Principal Investigator
Investigator:
Last name:
Hong Wei Tan
Email:
Principal Investigator
Investigator:
Last name:
Qin Wu
Email:
Principal Investigator
Start date:
November 30, 2023
Completion date:
December 31, 2026
Lead sponsor:
Agency:
Zhejiang Cancer Hospital
Agency class:
Other
Source:
Zhejiang Cancer Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06140576
