Advanced solid tumor, breast cancer
Conditions
Interventions
20mg:The drug is taken once daily for 21 days and then stopped for 7 days
40mg:The drug is taken once daily for 21 days and then stopped for 7 days
80mg:The drug is taken once daily for 21 days and then stopped for 7 days
100mg:The drug is taken once daily for 21 days and then stopped for 7 days
120mg:The drug is taken once daily for 21 days and then stopped for 7 days
140mg:The drug is taken once daily for 21 days and then stopped for 7 days
Sponsors
Fudan University Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Patients who meet all of the following criteria will be considered for inclusion: 1) All subjects or legal guardians must personally sign an informed consent form approved by the ERB prior to the commencement of any screening process; 2) Aged 18-75 years (including boundary value); 3) Patients with recurrent and/or metastatic advanced solid tumors confirmed histologically or cytologically, who do not have or are unable to receive standard treatment or who fail or are intolerable to standard treatment (this rule is limited to stage Ia only); 4) or premenopausal/perimenopausal women after menopause (including always conducted bilateral oophorectomy, or natural state after menopause, or medication designed to postmenopausal state), in patients with pathological detection diagnosis of HR +, HER2 breast cancer, with focal evidence of recurrence or metastasis, not suitable for to heal the surgery or radiation therapy for the purpose of (this is limited to the Ib); 5) Phase Ib cohort 1: The following criteria are required: always has never received any focal recurrent or metastatic disease of systemic cancer treatment; as strong as ever received endocrine drugs adjuvant therapy (at least for 2 years in endocrine drugs) postoperative patients, should be completed after 12 months of imaging examination confirmed disease recurrence; Phase Ib cohort 2: (1) Patients with recurrent and metastatic diseases are allowed no more than first-line chemotherapy; (2) Previous endocrine therapy should meet the following criteria: recurrent metastatic disease stage to accept 1 line endocrine therapy 6 months or more, imaging examination confirmed disease progression; as strong as ever received endocrine drugs adjuvant therapy (at least for 2 years in endocrine drugs after), during or after the treatment of 12 months imaging examination confirmed disease recurrence; 6) At least one measurable target lesion according to RECIST V1.1; Tumor lesions that have received previous radiotherapy or other local treatments are considered measurable only if disease progression at the treatment site is clearly documented after completion of treatment; 7) Patients without central nervous system metastasis, or patients with central nervous system metastasis who have been clinically and radiologically stable for more than 4 weeks (for asymptomatic patients with brain metastasis without any treatment, the number of metastatic lesions should be = 12 weeks; 9) ECOG (Eastern Oncology Collaboration Group) score was 0 or 1; 10) Patients meet the following laboratory test requirements during the screening period: Bone marrow reserve (Subjects may not meet this requirement by blood transfusion or granulocyte colony stimulating factor within 14 days prior to screening): absolute neutrophil count (ANC) acuity 1.5 x 10^9 / L; platelet p 100 x 10^9 / L; hemoglobin or 90 g/L; Kidney function: serum creatinine 1.5 times the upper limit of normal (ULN) or less, or; creatinine clearance rate (CCr) or 60 ml/min, the calculation formula is: male CCr = [(140 - age) by weight (kg)] / [0.818 x Scr (mu mol/L)] or CCr = (140 - age) by weight (kg) / 72 x Scr (mg/dl), women should be above the formula to calculate the results obtained by 0.85; Liver function: total bilirubin acuities were 1.5 x ULN, hepatocellular carcinoma, hepatic metastases patients or with clear Gilbert syndrome (non combined
Exclusion criteria
Exclusion criteria: Patients meeting any of the following criteria were not included in the study: 1) People who are known to be allergic to any active ingredient or excipient (including lactose monohydrate, etc.) of YZJ-2440 Maleate Tablet; 2) People with known allergy to anastrozole, letrozole (Phase Ib Cohort 1 only) or fluvestone (Phase Ib Cohort 2 only) for any of the active ingredients or excipients; 3) Previous use or current use of anti-tumor drugs targeting CDK4/6; 4) Previous or ongoing use of Fluvelisquine or everolimus (Phase Ib Cohort 2 only); 5) patients with a history of organ transplantation or who are preparing for organ transplantation; 6) Participated in other clinical trials or planned to participate in other clinical trials in this study within 28 days before the first administration of the study drug; 7) Use of any systemic antitumor therapy within 28 days prior to the first dosing of the study drug (limit to 2 weeks for endocrine therapy and herbal medicines with antitumor effects, limit to 6 weeks for mitomycin or nitrosamines); 8) Patients who received major surgical treatment, open biopsy, or significant traumatic injury within 2 weeks prior to the first administration of the study drug (in all cases, patients must fully recover and stabilize before treatment begins); 9) People with other concurrent, severe and uncontrollable systemic diseases; 10) Have a history of gastrointestinal tract disease that is clinically difficult to control or present disease, such as inability to swallow, uncontrollable nausea and vomiting, chronic diarrhea, intestinal obstruction or other chronic gastrointestinal diseases, unable to swallow drug preparations or may affect the intake, transport or absorption of drugs, or have undergone total gastrectomy before; 11) Patients with rare genetic diseases such as galactose intolerance, LAPP lactase deficiency or malabsorption of glucose-galactose; 12) Had other malignant tumors in the past 5 years, except basal cell carcinoma of the skin and carcinoma in situ of the cervix, which were treated with radical therapy; 13) Pregnant or lactating female patients; 14) Cardiac dysfunction according to any of the following definition: CTCAE V5.0 grading criteria of 3 or more symptomatic congestive heart failure (CHF) or New York heart association (NYHA) classification standard of grade 2 or more history, history of myocardial infarction, heart failure, need to drug treatment of angina pectoris, without sufficient medication to control severe arrhythmia, severe conduction block, uncontrolled hypertension (160 MMHG systolic blood pressure or greater acuity 100 MMHG) and/or diastolic blood pressure, or clinically significant vascular disease; 15) Artery/venous thrombosis events, such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage and cerebral infarction), deep venous thrombosis and pulmonary embolism, occurred within 6 months before the first medication; 16) Interstitial pulmonary disease or pulmonary fibrosis (patients with radiation/local interstitial pulmonary disease or stable disease recovery for 3 months or more were allowed to be included); 17) Any uncontrolled serious clinical trial-related problems (such as substance abuse, uncontrolled psychotic state or cognitive impairment, uncontrolled pleural effusion and/or pericarpericidal effusion, uncontrolled complications, including active infection, arterial thrombosis, and symptomatic pulmonary embolism); 1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety evaluation index;Efficacy evaluation index;PK; | — |
Countries
China
Contacts
Public ContactJiang Taotao
Outcome results
None listed