small cell lung cancer
Conditions
Interventions
Experimental group:6-Mercaptopurine
Sponsors
Lung Cancer Center, West China Hospital, Sichuan Uiversity
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: (1) The subjects voluntarily joined the study, signed the informed consent, had good compliance, and cooperated with follow-up; (2) Male or female patients aged 18-75 years; (3) Pathologically confirmed patients with extensive stage small cell lung cancer who have failed standard third-line therapy in the past, or patients with extensive stage small cell lung cancer who have failed standard second-line therapy and refused third-line anlotinib therapy, and have measurable target lesions; ? Treatment failure is defined as disease progression or intolerance during or after chemotherapy treatment. The original treatment regimen was defined as the first-line treatment for patients in the local period who had previously received concurrent chemoradiotherapy or adjuvant chemotherapy if recurrence/metastasis occurred within 6 months after the end of the previous treatment. (4) The subjects can provide archived tumor tissue samples or fresh tumor samples can be biopsied and confirmed as co-deletion and/or co-silence of RB1-NUDT15 by fluorescence in situ hybridization (FISH) and immunohistochemical staining (IHC) in the central laboratory; (5) The interval between the time of disease progression and the end of the last systemic chemotherapy is no more than 6 months; (6) Life expectancy of at least 3 months, ECOG score: 0-1; (7) Major organ function is normal, that is, meet the following criteria: 1) The standard of blood routine examination should be met (no blood transfusion and blood products within the first 14 days, no G-CSF and other hematopoietic stimulating factors are used to correct) : ? Hemoglobin (HB) =90 g/L; ? neutrophil absolute value (ANC) =1.5×109/L (1500/m3); ? Platelet count (PLT) =100×109/L; 2) Biochemical examination shall meet the following standards: ? Total bilirubin (TBiL) =1.5?ULN; For subjects with liver metastases or with evidence/suspicion of Gilbert disease, the TbiL=3?ULN; ? ALT and AST=2.5?ULN, while in subjects with liver metastasis, ALT and AST=5?ULN; ? serum creatinine (Cr) =1.5?ULN or endogenous creatinine clearance (CrCl) =50 ml/min (Cockcroft-Gault formula: CrCL (mL/min) =[(140 -- age)* Body weight (kg)* F]/(SCr(mg/dL)*72. Male F=1, female F=0.85, SCr= serum creatinine) (8) Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) = the lower limit of normal value (50%); (9) Women of reproductive age must have been using reliable contraception or had a pregnancy test (serum or urine) negative within 7 days prior to enrollment and be willing to use an appropriate method of contraception during the trial period and 8 weeks after the last dose of the test drug. For men, consent is required to use an appropriate method of contraception or to have been surgically sterilized during the trial period and 8 weeks after the last dose of the trial drug.
Exclusion criteria
Exclusion criteria: (1) Patients with TPMT or NUDT15 gene germ line mutation for anticoagulation by PCR gene sequencing; (2) Imaging (CT or MRI) shows the presence of significant pulmonary cavity tumor; (3) Medical history and complications 1) Patients with symptomatic brain metastases, cancerous meningitis, spinal cord compression, or imaging CT or MRI at screening Brain or pia diseases were found by examination (patients with brain metastases who had completed treatment 4 weeks before enrollment and had stable symptoms without progression could be enrolled, but they were confirmed to be asymptomatic by brain MRI, CT or venography evaluation); 2) The patient is participating in other clinical studies (except non-interventional studies) or has less than 4 weeks since the end of treatment in the previous clinical study; 3) Had received chemotherapy, radiotherapy, or other investigational anticancer therapy (except bisphosphonates) within 4 weeks prior to the first dose of the investigational drug: Those who had previously received local radiotherapy were eligible for admission if the following conditions were met: more than 4 weeks from the end of radiotherapy to the start of study therapy (more than 2 weeks for brain radiotherapy); And the target lesions selected in this study were not in the radiotherapy area; Or the target lesion is located in the radiotherapy area, but progress has been confirmed; 4) Present or present with other malignancies within 5 years, except cured cervical carcinoma in situ, non-melanoma skin cancer and superficial bladder tumors [Ta (non-invasive tumor), Tis (cancer in situ) and T1 (tumor infiltrating basal membrane)]; 5) Have an active, known, or suspected autoimmune disease, including a history of allogeneic organ transplantation, a history of allogeneic hematopoietic stem cell transplantation, an HIV-positive history, or a history of acquired immune deficiency syndrome (AIDS). The following exceptions: Vitiligo, hair loss, Grave's disease, psoriasis, or eczema that did not require systemic treatment within the last 2 years, stable hypothyroidism (caused by autoimmune thyroiditis) with no symptoms or stable dose of hormone replacement therapy only, type 1 diabetes requiring stable dose of insulin replacement therapy only, or childhood asthma that has been in complete remission, Subjects who do not require any intervention as adults, or who suffer from diseases that do not recur in the absence of external triggers. 6) Active or previously documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis). 7) Subjects requiring systemic treatment with corticosteroids (> 10mg/ day equivalent dose of prednisone) or other immunosuppressive drugs within 14 days prior to study drug administration. However, the following conditions can be included: ? If there is no active autoimmune disease, treatment with inhaled or topical steroids and adrenal corticosteroids at a therapeutic dose > 10mg/ day of prednisone is permitted; ? Physiological doses of systemic glucocorticoids did not exceed 10mg/ day of prednisone or equivalent doses of other glucocorticoids. ? Glucocorticoids as prophylactic for hypersensitivity (e.g. before CT). ? systemic sex hormone therapy has been discontinued for more than 2 weeks. 8) Patients whose antitumor treaty-related adverse reactions (except alopecia) did not recover to NCI-CTCAE= class 1 after previous systemic antitumor treatment; 9) Abnormal coagulation function (INR >1.5 or prothrombin tim
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| recommended phase 2 dose, RP2D;objective response rate,ORR; | — |
Secondary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose (MTD), dose-limited toxicity (DLTs), safety, plasma PK parameters;Progression-free survival (PFS);overall survival (OS);Disease Control Rate (DCR); | — |
Countries
China
Contacts
Public ContactYan Zhang
Lung Cancer Center, West China Hospital, Sichuan Uiversity
Outcome results
None listed