Study of Pazopanib Combined With Palbociclib for Refractory Solid Tumors With Co-amplified in the 11q13(FGF3/4/19/CCND1)

Inclusion Criteria:

1. Voluntarily join this study and sign an informed consent form;
2. ≥ 18 years old;
3. Patients with metastatic solid tumors diagnosed by histology or cytology; Queue 1:11q13 co amplified or FGFR1/FGFR2 amplified urothelial carcinoma Queue 2: Head and neck squamous cell carcinoma co amplified in 11q13 region Queue 3:11q13 co amplified other solid tumors
4. Disease progression or intolerable toxicity confirmed by imaging during or after treatment with at least two standard treatment regimens in the past;
5. According to RECIST 1.1, there must be at least one measurable lesion;
6. Can swallow pills normally;
7. ECOG score: 0-2;
8. Expected survival period ≥ 12 weeks;
9. The function of important organs meets the following requirements (no blood components or cell growth factor drugs are allowed to be used within 14 days before the first medication):

   Absolute neutrophil count ≥ 1.5 × 109/L; Platelets ≥ 100 × 109/L; Hemoglobin ≥ 90 g/L; Serum albumin ≥ 30 g/L; Serum total bilirubin ≤ 1.5 × ULN; ALT and AST ≤ 2.5 × ULN, and if there is liver metastasis, ALT and AST ≤ 5ULN; AKP≤ 2.5×ULN；Serum creatinine ≤ 1.5 × ULN; International normalized ratio (INR) ≤ 1.5 (not receiving anticoagulant therapy);
10. Non surgical sterilization or female patients of childbearing age are required to use a medically approved contraceptive measure (such as intrauterine device, contraceptive pill, or condom) during the study treatment period and within 3 months after the end of the study treatment period; Female patients of childbearing age who undergo non-surgical sterilization must have a negative serum or urine HCG test within 7 days prior to their first medication; And it must be during non lactation period; For male patients whose partners are women of childbearing age, effective contraception methods should be used during the trial period and within 3 months after the last administration of the trial drug.

Exclusion Criteria:

1. Known history or evidence of interstitial lung disease or active non infectious pneumonia;
2. Known to have central nervous system metastases;
3. Within the past 5 years or simultaneously with other malignant tumors (excluding cured skin basal cell carcinoma and cervical carcinoma in situ);
4. Suffering from hypertension and unable to achieve good control with antihypertensive medication (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg); Allow the above parameters to be achieved through the use of antihypertensive therapy; Previously experienced hypertensive crisis or hypertensive encephalopathy;
5. There are uncontrolled clinical symptoms or diseases of the heart, such as: (1) NYHA grade 2 or above heart failure, (2) unstable angina pectoris, (3) myocardial infarction within 1 year, (4) clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention, (5) QTc\>450ms (male); QTc\>470ms (female);
6. For those undergoing thrombolytic or anticoagulant therapy, prophylactic use of low-dose aspirin and low molecular weight heparin is allowed;
7. Within the first 3 months of enrollment, there have been significant clinical bleeding symptoms or clear bleeding tendencies; If fecal occult blood is positive during the baseline period, a follow-up examination can be conducted. If the result is still positive after the follow-up examination, gastroscopy examination is required;
8. Tumor invasion of important blood vessels, or the possibility of tumor invasion of important blood vessels in the future research period determined by imaging, may lead to fatal bleeding;
9. If the patient has pleural effusion, ascites, or pericardial effusion that requires drainage, and the researcher evaluates the symptoms to be stable after drainage, they can be enrolled;
10. Occurrence of arterial/venous thrombosis events within the first 6 months of enrollment, such as cerebrovascular accidents (including temporary ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;
11. Known genetic or acquired bleeding and thrombophilia tendencies (such as in hemophilia patients, coagulation dysfunction, etc.);
12. Within 6 months prior to the start of treatment, there has been an abdominal fistula, gastrointestinal perforation, or abdominal abscess;
13. Significant vascular disease (such as aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) occurred within 6 months prior to the start of the study treatment;
14. Severe, unhealed, or cracked wounds, as well as active ulcers or untreated fractures;
15. Received major surgical treatment (excluding diagnosis) within 4 weeks before the start of the study treatment or expected to undergo major surgical treatment during the study period;
16. Urine routine shows that urine protein is ≥++and has been confirmed to have a 24-hour urine protein level\>1.0 g;
17. Previously received radiotherapy (excluding palliative radiotherapy for bone lesions), chemotherapy, surgery (excluding biopsy), and less than 4 weeks before the first study medication after completion of treatment (last medication); The last dose of antibody administration is less than 4 weeks after the first study medication; Molecular targeted therapy (including other oral targeted drugs used in clinical trials) for patients with less than 5 drug half lives from the first study drug, or adverse reactions caused by previous treatment (excluding hair loss) that have not recovered to ≤ CTCAE grade 1;
18. Suffering from active infection, having unexplained fever ≥ 38.5 ℃ within 7 days before medication, or baseline white blood cell count\>15 × 109/L;
19. Suffering from congenital or acquired immune dysfunction (such as HIV infected individuals); Hepatitis B surface antigen (HBsAg) positive and hepatitis B virus deoxyribonucleic acid (HBV DNA) ≥ 2000 IU/ml, or hepatitis C virus antibody positive;
20. Previously received anti angiogenic therapy;
21. According to the researchers' judgment, the patient may have other factors that may affect the research results or cause the study to be terminated midway, such as alcohol abuse, drug abuse, other serious illnesses (including mental illnesses) that require concomitant treatment, serious laboratory test abnormalities, and family or social factors that may affect the patient's safety.