Trial Title:
Milaberon in Advanced Solid Tumors: an Open, Multicenter Clinical Study
NCT ID:
NCT06534762
Condition:
NSCLC
SCLC
Colorectal Cancer
Pancreas Cancer
TNBC - Triple-Negative Breast Cancer
DLBCL - Diffuse Large B Cell Lymphoma
Squamous Cell Carcinoma of Head and Neck
Conditions: Official terms:
Colorectal Neoplasms
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Triple Negative Breast Neoplasms
Pancreatic Neoplasms
Squamous Cell Carcinoma of Head and Neck
Mirabegron
Conditions: Keywords:
Lung Cancer
Pancreas Cancer
Breast Cancer
B cell lymphoma
Colorectal Cancer
Carcinoma of Head and Neck
Miraberon
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Mirabegron
Description:
To explore the efficacy and safety of milaberon combined with standard treatment in
advanced solid tumors
Arm group label:
Miraberon
Summary:
This study is an exploratory study, and all the drugs involved are listed drugs. The
dosage of mirabetron is selected according to the basis of previous research. The
clinical recommend dose of this product is 50mg/day, and the dose used in this study is
100mg/day, which is larger than the clinical commonly used dose. The main adverse
reactions of this product are urinary tract infection and rapid heartbeat. In the
clinical study, we will focus on the urine routine and heart-related adverse events of
the subjects, and deal with the adverse events in time.
Subjects were given mirabeeron 100mg/day orally once a day in the morning until disease
progression. When there are related or possible related side effects of the study drug
mirabeeron, and according to NCI-CTCAE V 5.0, when subjects have more than or equal to
grade 3 related toxicity, the administration should be delayed until grade 2 or lower to
baseline, and the dose will be reduced by 50%, and subsequent dose increase is not
allowed. If the pre-dose criteria are not met within 28 days, the drug will be
permanently discontinued.
Detailed description:
Cohort A non-small cell lung cancer (NSCLC):
A1 non-squamous cell carcinoma, Sintilimab or tislelizumab(3 mg/kg) pemetrexed(500mg/m2)
cisplatin(75mg/m2) or carboplatin (AUC 5) q3w, 4-6 cycles of induction chemotherapy,
Sintilimab or tislelizumab + pemetrexed maintenance, q3w; A2 squamous cell carcinoma,
Sintilimab or tislelizumab(3 mg/kg) nab-paclitaxel (100mg/m2 d1/8/15) carboplatin (AUC 5)
q3w,4-6 cycles, Sintilimab or tislelizumab maintenance, q3w; Cohort B Small cell lung
cancer (SCLC) Serplulimab (4.5 mg/kg, D1) Carboplatin (AUC 5,D1) Etoposide (100 mg/m 2,
D1-3),q3w, Cycle 4-6, Serplulimab maintained q3w Cohort C Colorectal cancer XELOX +
bevacizumab (7.5 mg/kg,D1),q3w,8 cycles, bevacizumab + capecitabine maintenance, q3w;
XELOX: oxaliplatin(130mg/m2 intravenous infusion> 2h D1), capecitabine (1000mg/m2 oral
bid,D1-14),q3w; If the primary tumor is in the left colon or rectum, RAS/BRAF is wild
type, cetuximab (500mg/m2,D1) + mFOLFOX6 is also admitted.
mFOLFOX6: oxaliplatin(85mg/m2, intravenous infusion 2h,D1) LV(400mg/m2, intravenous
infusion 2h,D1) 5-FU (400mg, intravenous push, D1, then 1200mg/(m2 * d)X2 days continuous
intravenous infusion), 12 cycles, bevacizumab + capecitabine maintenance, q3w Cohort D
Pancreatic cancer GEM + nab-paclitaxel regimen, GEM(1000mg/m2) nab-paclitaxel(125mg/m2)
,D1,8, 15,q4w,6-8 cycles Adjustable GEM + nab-paclitaxel regimen, GEM(1000mg/m2)
nab-paclitaxel(125mg/m2) ,D1, 8,q3w,6-8 cycles Cohort E Triple-Negative Breast Cancer TX
regimen: docetaxel(75mg/m2 D1),q3w or nab-paclitaxel(100-150mg/m2
D1,qw),capecitabine(1000mg/m2 oral bid,D1-14),q3w,6-8 cycles; capecitabine maintenance,
q3w (taxmen treatment sensitive) GP regimen: GEM(1000mg/m2 ,D1, 8) cisplatin(75mg/m2
,divided into D1-3) q3w (taxane treatment failure) Cohort F Diffuse large B- cell
lymphoma R-CHOP 6 cycles then R 2 cycles; R-CHOP: rituximab(375mg/m2,D0)
cyclophosphamide(750mg/m2 D1),doxorubicin(40-50mg/m2,D1) vincristine(1.4mg/m2 D1 ,maximum
dose 2mg) prednisone(100mg,D1-5 mg), q3w Cohort G Head and neck squamous cell carcinoma
G1 Recurrent/metastatic squamous cell carcinoma of head and neck (non-nasopharyngeal
carcinoma) PF: Cisplatin(100mg/m2 D1) or Carboplatin(AUC 5 D1), 5-Fu(1000mg/m2 d1-4),q3w
TP: paclitaxel(175mg/m2 D1) cisplatin (75mg/m2 d1), q3w G2 Recurrent/Metastatic
Nasopharyngeal Squamous Cell Carcinoma GP+Camrelizumab or Tislelizumab: cisplatin(80mg/m2
d1) gemcitabine (1000mg/m2 d1,8), then camrelizumab or tislelizumab 200mg,q3w maintenance
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients voluntarily participate in the study, sign informed consent, and have good
compliance;
- 18-65 years old (including 18 and 65 years old);
- solid tumors confirmed by histology and/or cytology, and advanced metastatic tumors
that are not feasible for surgical resection;
- Has not received previous systemic antitumor drug therapy for metastatic/recurrent
solid tumors;
- For subjects who have previously received neoadjuvant/adjuvant therapy, it takes
more than 6 months from the last treatment to relapse or progression;
- Recovery of previous treatment-related AEs to National Cancer Institute Terminology
Criteria for Common Adverse Events (NCI-CTCAE)≤ Grade 1 (excluding alopecia);
- According to RECIST 1.1 standard, there is at least one measurable lesion assessed
by the research center, and the measurable lesion should be a lesion that has not
received local treatment such as radiotherapy (the lesion located in the region of
previous radiotherapy can also be regarded as a measurable lesion that meets the
requirements if progress is confirmed);
- ECOG physical condition: 0-1;
- Expected survival ≥ 12 weeks;
- The function of major organs is normal, I .e. the following criteria are met (no
blood transfusion, albumin, recombinant human thrombopoietin or colony stimulating
factor [CSF] treatment has been received within 14 days before the first study drug
administration): blood test (absolute value of neutrophils ≥ 1.5 × 109/L, platelets
≥ 100 × 109/L, hemoglobin concentration ≥ 9g/dL); Liver function test (bilirubin ≤
1.5 × ULN; aspartate aminotransferase and glutamate aminotransferase ≤ 2.5 ×ULN, AST
and ALT ≤ 5 ×ULN in case of liver metastasis); renal function (serum creatinine ≤
1.5 ×ULN, or creatinine clearance rate (CCr)≥ 60 ml/min); coagulation function,
international normalized ratio (INR)≤ 1.5 ×ULN, prothrombin time (PT) and activated
partial thromboplastin time (APTT)≤ 1.5 ×ULN; thyroid function, thyroid-stimulating
hormone (TSH)≤ the upper limit of normal (ULN); FT3 and FT4 levels should be
examined if abnormal, and FT3 and FT4 levels are normal; (11) Women of childbearing
age must have a negative serum pregnancy test within 14 days prior to treatment and
be willing to use medically approved effective contraception during the study period
and within 3 months after the last dose of study medication (e. g. IUDs,
contraceptives or condoms; surgical sterilization is required for male subjects
whose partner is a woman of childbearing age, alternatively, an effective method of
contraception is recommended for the duration of the study and for 3 months after
the last study dose.
Exclusion Criteria:
- Received the following treatment within 4 weeks before treatment: radiotherapy of
tumor, major surgical operation or wound has not been completely healed, β3
adrenoceptor agonist and corresponding clinical research drugs;
- those who have contraindications to Miraberon: those who are allergic to Miraberon
or any of its excipients;
- Active malignant tumors in the past 3 years, except for tumors participating in the
study and local tumors that have been cured, such as skin basal cell carcinoma, skin
squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ,
breast carcinoma in situ, etc;
- symptomatic brain or meningeal metastases; Severe infection (such as intravenous
infusion of antibiotics, antifungals, or antivirals) within 4 weeks before
treatment, or fever of unknown origin> 38.5°C during screening/first dose;
- have high blood pressure that cannot be well controlled by antihypertensive drug
therapy (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg);
- Within 3 months before treatment, there were obvious clinical bleeding symptoms or
obvious bleeding tendency (bleeding> 30 mL within 3 months, hematemesis, black
stool, hematochezia), hemoptysis (fresh blood> 5 mL within 4 weeks), etc. or a
venous/venous thrombotic event within 6 months prior to treatment, such as a
cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage,
cerebral infarction), deep vein thrombosis, and pulmonary embolism; or the need for
long-term anticoagulant therapy with warfarin or heparin, or the need for long-term
antiplatelet therapy (aspirin ≥ 300 mg/day or clopidogrel ≥ 75 mg/day);
- The tumor is found to invade large vascular structures during screening, such as
pulmonary artery, superior vena cava or inferior vena cava, and the researchers
judge that there is a greater risk of bleeding;
- Active heart disease, including myocardial infarction, severe/unstable angina
pectoris, 6 months before treatment. Echocardiography left ventricular ejection
fraction <50%, arrhythmia poorly controlled;
- Uncontrollable pleural effusion, pericardial effusion or ascites requiring frequent
drainage after appropriate intervention;
- Presence of any active autoimmune disease or history of autoimmune disease,
including but not limited to: autoimmune hepatitis, interstitial pneumonia,
pulmonary fibrosis, uveitis, enteritis, hepatitis, hypophysitis, vasculitis,
nephritis, thyroid function progression, decreased thyroid function; Note:(1)
Subjects whose thyroid function can only be controlled by hormone replacement
therapy can be included;(2) Subjects with skin diseases that do not require systemic
treatment, such as vitiligo, psoriasis, alopecia, type 1 diabetes, or childhood
asthma has been completely resolved, and no intervention can be included after
adulthood;(3) Patients with asthma who require medical intervention with
bronchodilators cannot be included;
- received treatment with live attenuated vaccine within 28 days prior to the first
administration of the study drug;
- The patient has a known history of psychotropic substance abuse, alcohol abuse or
drug abuse; a history of definite neurological or psychiatric disorders, including
epilepsy or dementia
- tuberculosis infection history;
- known human immunodeficiency virus (HIV) infection;
- Known history of clinically significant liver disease, including viral hepatitis
[Known hepatitis B virus (HBV) carriers must exclude active HBV infection, I .e.,
HBV DNA positive (>1 × 104 copies/mL or> 2000 IU/mL);
- Known hepatitis C virus infection (HCV) and HCV RNA positive (>1 x 103 copies/mL),
or other hepatitis, cirrhosis];
- Patients with renal injury: GFR<30 mL/min 1.73m2 or patients requiring hemodialysis
- any other medical condition, clinically significant metabolic, physical, or
laboratory abnormality, which, in the investigator's judgment, would reasonably
suspect that the patient has a disease or condition that is not appropriate for the
study drug (e. g., having seizures requiring treatment, bladder outlet obstruction,
anxiety), or would interfere with the interpretation of the study results, or place
the patient in a high-risk situation, or patients considered by the investigator to
be unsuitable for inclusion.
Gender:
All
Minimum age:
18 Years
Maximum age:
65 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Zhejiang Provincial People's Hospital
Address:
City:
Hangzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Liu Yang, M.D.
Phone:
13666601475
Email:
yangliuqq2003@163.com
Investigator:
Last name:
Minghua Ge, M.D.
Email:
Principal Investigator
Start date:
July 15, 2024
Completion date:
July 1, 2028
Lead sponsor:
Agency:
Zhejiang Provincial People's Hospital
Agency class:
Other
Source:
Zhejiang Provincial People's Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06534762
