KRAS mutant advanced solid tumors
Conditions
Interventions
Phase I dose exploration:Almonertinib+Palbociclib
Single arm Phase II:Almonertinib+Palbociclib
Sponsors
Sun Yat sen University Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. >= 18 and 6 months after completion of adjuvant therapy, the adjuvant therapy will not be counted as a prior treatment regimen. 6. Patients who have received prior radiotherapy are eligible for enrollment, provided that: the irradiated area involves = 1.5×10^9/L; PLT>= 100×10^9/L; Hb>= 100g/L. -The biochemical examination must meet the following criteria: TBIL= 50ml/min(Cockcroft-Gault formula). 8. Female subjects of childbearing potential must have either practiced reliable contraceptive methods or undergone a pregnancy test (serum or urine) within 7 days prior to enrollment with negative results, and must be willing to use appropriate contraceptive methods during the trial period and for 8 weeks after the last administration of the investigational drug. Male subjects must agree to use appropriate contraceptive methods during the trial period and for 8 weeks after the last administration of the investigational drug, or have been surgically sterilized. 9. Subjects must voluntarily participate in the study, sign an informed consent form, demonstrate good compliance, and actively cooperate with follow-up procedures. 10. Subjects are requested to provide, whenever possible, previous tumor tissue paraffin blocks (or 5-15 pathological biopsy sections [unstained slides]) and peripheral blood specimens (10ml), and to cooperate with investigators during treatment for tumor biopsy sampling when feasible, to support exploratory research on tumor biomarker detection.
Exclusion criteria
Exclusion criteria: 1. Exclusion applies to patients who had symptomatic CNS metastases, leptomeningeal metastases, or spinal cord compression caused by metastatic lesions prior to signing the informed consent form. 2. Patients with prior or current use of CDK4/6-targeted anticancer agents. 3. Molecular targeted therapy or radiotherapy within 2 weeks prior to screening; Chemotherapy or immunotherapy within 3 weeks prior to screening; Nitrosoureas or mitomycin administration within 6 weeks prior to screening; Prior radical radiotherapy involving >= 25% of bone marrow, inclusion eligibility subject to investigator evaluation. 4. Major surgery performed within 6 weeks prior to screening, or planned major surgery within 12 weeks after initiation of the investigational drug. 5. Patients who have participated in other clinical studies with active treatment exposure within 28 days before the first investigational drug dose are ineligible. 6. Third-space fluid accumulations refractory to drainage or therapeutic interventions exist (such as massive pleural effusions, ascites, and pericardial effusions). 7. Active inflammatory bowel disease, chronic diarrhea, intestinal obstruction, dysphagia, or the presence of multiple factors that impair drug administration and absorption. 8. Uncontrolled electrolyte disturbances (e.g., hypocalcemia, hypokalemia, hypomagnesemia). 9. Individuals with allergic predisposition or a history of severe allergic reactions. 10. Active hepatitis B virus (HBV) infection; active hepatitis C virus (HCV) infection; history of immunodeficiency. 11.Documented long QT syndrome (congenital/acquired) or familial LQTS with genetic confirmation; significant ventricular arrhythmias (e.g., sustained VT/VF), ongoing antiarrhythmic therapy, or ICD implantation; grade 3+ (CTCAE v5.0) cardio/cerebrovascular events within 6 months pre-dosing; NYHA functional class III-IV. 12. Suffers from severe lung disease (interstitial lung disease, severe chronic obstructive pulmonary disease [COPD], severe pulmonary insufficiency, and a history of symptomatic bronchospasm). 13. Pregnant or lactating women; women of childbearing potential with a positive baseline pregnancy test; and women of childbearing age or male patients with partners of childbearing age who are unwilling to use effective contraception throughout the trial period. 14. Presence of concomitant diseases deemed by the investigator to pose significant risks to patient safety or compromise study completion. 15. Documented history of neurological or psychiatric disorders, including epilepsy or dementia. 16. Other conditions deemed by the investigator to preclude safe and appropriate study participation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety;Objective Response Rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression-free Survival;Disease control rate, DCR;Overall survival, OS;Quality of life, QoL; | — |
Countries
China
Contacts
Public ContactZhangli/Zhao Hongyun
Sun Yat-sen University Cancer Center
Outcome results
None listed