Advanced solid tumor
Conditions
Interventions
1 group:Dosing 40mg/day
2 group:Dosing 80mg/d
3 group:Dosing 120mg/d
4 group:Dosing 160mg/d
5 group:Dosing 200mg/d
6 group:Dosing 240mg/d
phase Ib in gastric cancer patients with ATM deficiency:Oral tablet SC0245, dose to be established
phase Ib esophageal carcinoma patients with p53 mutation:Oral tablet SC0245, dose to be established
Sponsors
Beijing Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Phase Ia: Patients of advanced solid tumor with histologically/cytologically proven of progression on standard therapy, or have no standard therapy; 2. Phase Ib: Patients with advanced gastric cancer or esophageal carcinoma with ATM deficiency/lost or p53 mutation confirmed by central laboratory that have progressed during or after standard therapy and might benefit from SC0245 as judged by the investigators; 3. Measurable disease with at least 1 target lesion by RECIST v1.1(patients with non-measurable but evaluable disease are also eligible as judged by investigators in Phase Ia); 4. Written informed consent to participate voluntarily; 5. Aged >= 18 years and = 3 months; 8. Adequate normal organ function measured during the screening period as defined below : Absolute neutrophil count (ANC) >= 1.5 x 10^9/L;Platelet count >= 100 x 10^9/L; Haemoglobin >= 90g/L, no blood transfusion or hematopoietic stimulating factor therapy received within 14 days; Liver function: Serum bilirubin = 30g/L; INR 50 mL/min; Fasting blood glucose <= 140 mg/dL(7.8 mmol/L); 9. Women of child-bearing potential must have negative serum pregnancy test within 7 days of study treatment. Women of child-bearing potential and male participants are required, and must be willing to use highly effective forms of contraception from the date of signing ICF to 6 months after the last dose of the study drug.
Exclusion criteria
Exclusion criteria: 1. Receipt of the last dose of anti-cancer therapy(chemotherapy, radiotherapy, biologic therapy, endocrine therapy, etc.)within 2 weeks of the first dose of study drug. Receipt of the last dose of nitrosourea or mitomycin C within 6 weeks of the first dose of study drug. Exposure to a small molecule targeted therapy within five half-lives, prior to first dose of study drug. 2. Receipt of any investigational product within 2 weeks of the first dose of study drug. 3. Major surgery or severe trauma within 2 weeks prior to first dose of study drug (needle biopsy excluded), or scheduled for selective surgery during the trial. 4. Receipt of traditional Chinese medicine with anti-tumor effect within 2 weeks of the first dose of study drug. 5. Any previous treatment with ATR inhibitor or other DDR related inhibitors(PARP inhibitors excluded). 6. Any unresolved toxicity NCI CTCAE Grade >= 2 from previous anticancer therapy with the exception of alopecia, pigmentation. Neurotoxicity NCI CTCAE Grade >= 3. 7. Central nervous system metastases that meet the following conditions: (1) Require local treatment(surgery, radiotherapy or others)(asymptomatic or symptomatic brain metastases for which local treatment is not required as judged by the investigators are eligible) ; (2) On-going requirement for > 10 mg of prednisone per day or an equivalent dose of other corticosteroid. 8. Active infection requiring treatment. 9. Positive result in any of HBsAg, anti-HCV, TPPA, anti-HIV test. 10. Heart function or disease meets one of the following conditions: (1) Mean resting corrected QT interval (QTc) > 470 msec, obtained from 3 12-lead electrocardiograms(ECGs)using the Bazett or Fredericia formula carried out in the research center during the screening period; (2) Cardiac arrhythmias of clinically significant, including but not limited to complete left bundle branch block, second-degree atrioventricular block; (3) Any factors that increase the risk of QTc prolongation, such as uncorrected hypokalemia, hereditary long QT syndrome, taking drugs that prolong QTc interval (mainly class IA, IC and III antiarrhythmic agents); (4) Congestive heart failure graded >= 3 as defined by New York Heart Association (NYHA). 11. Active digestive disease, previous significant gastrointestinal surgery, malabsorption syndrome, or other conditions that would impair the absorption of study drug (such as ulcerative diseases, refractory nausea and vomiting, diarrhea, malabsorption, and small intestine resection). 12. Uncontrolled hypertension (blood pressure of general patients >=b140/90 mmHg but in high-risk patients >=b130/80 mmHg) and diabetes mellitus(HbA 1c >=b7%). 13. Receipt of strong CYP3A inhibitors (amprenavir, atazanavir, boceprevir, clarithromycin, conivaptan, delavirdine, diltiazem, erythromycin, fosamprenavir, indinavir, itraconazole, ketoconazole, lopinavir, mibefradil, miconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, verapamil, voriconazole, etc.) or strong CYP3A inducers (carbamazepine, felbamate, nevirapine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentine, etc.) within 14 days prior to the first dose of study drug. 14. Lactating women.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose limiting toxicity, DLT; | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety endpoints;Progression-free survival;Overall survival;Objective response rate;Disease control rate; | — |
Countries
China
Contacts
Public ContactShen Lin
Beijing Cancer Hospital
Outcome results
None listed