Small Cell Lung Cancer Extensive Stage
Conditions
Keywords
Fluzoparib, Apatinib, Small Cell Lung Cancer
Brief summary
This open-label, dose finding phase Ib trial studies the tolerability and the best dose of fluzoparib in combination with apatinib and to see how well these two drugs work together as second-line treatment of patients with extensive stage small cell lung cancer. The safety and efficacy of fluzoparib in combination with apatinib will be explored. Both dose escalation and dose expansion parts are included in this study.
Detailed description
The degree of malignancy of small cell lung cancer is extremely high. About 60% to 70% of patients are diagnosed as extensive. The median survival time of the disease is only 9 to 10 months, and the 2-year survival rate is less than 10%. Fluzoparib is an oral potent, selective poly-ADP ribose polymerase-1 (PARP-1) and PARP-2 inhibitor. Apatinib is an oral selective vascular endothelial growth factor receptor (VEGFR) inhibitor.This open-label, dose finding phase Ib trial studies the tolerability and the best dose of fluzoparib in combination with apatinib as second-line treatment of patients with extensive stage small cell lung cancer. The safety and efficacy of fluzoparib in combination with apatinib will be explored.
Interventions
DRUGFluzoparib
Take Fluzoparib orally（either at 50,100mg bid）until disease progression or appearance of unbearable toxicity
DRUGApatinib
Take apatinib orally (either at 375mg、500mg、750mg qd）until disease progression or appearance of unbearable toxicity
Sponsors
Tianjin Medical University Second Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Patients with Extensive Stage Small Cell Lung Cancer diagnosed by pathology (histology or cytology) (according to WHO classification in 2015); 2. Failure of first-line treatment； 3. Age 18-70 years old; 4. ≤21 days before the first study drug, CT or MRI scan, at least one target lesion without previous radiotherapy as defined by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1); 5. PS score: 0-2; the expected survival time ≥ 12 weeks; 6. No anti-angiogenesis drugs or PARP inhibitors have been used in previous treatments; 7. All acute toxic reactions caused by previous anti-tumor treatments or surgical operations were relieved before the screening period 0-1 grade (according to NCI CTCAE 5.0 judgment) or to the level specified by the inclusion/
Exclusion criteria
(hair loss and other researchers believe that the subjects are not Except for toxicity that poses a safety risk); 8. No blood transfusion or blood products, no correction with G-CSF and other hematopoietic stimulating factors within 14 days before the first administration. First research before investigating drugs, laboratory test values meet the following conditions: 1. Blood routine: white blood cell count (WBC) ≥3.0 × 109/L; absolute neutrophil count (ANC) ≥1.5 × 109/L; Platelet (PLT) ≥100 × 109/L; Hemoglobin content (HGB) ≥9.0 g/dL; 2. Liver function: Aspartate aminotransferase (AST) ≤2.5 x ULN in subjects without liver metastasis, alanine liver aminotransferase (ALT) ≤2.5 x ULN; ALT and AST in subjects with liver metastases \<5 x ULN; Serum total bilirubin (TBIL) ≤1.5 x ULN (except Gilbert syndrome total bilirubin \<3.0 mg/dL); Albumin (ALB) ≥3 g/dL; 3. Renal function: serum creatinine ≤1.5 x ULN or creatinine clearance CrCl≥40 mL/minute; 4. Coagulation function: International normalized ratio (INR) ≤ 1.5, activated partial thromboplastin time (APTT) ≤ 1.5 x ULN; 5. Others: Lipase ≤ 1.5 x ULN, if lipase\> 1.5 x ULN but no clinical or imaging confirmed pancreatitis can be included; amylase ≤ 1.5 x ULN, if amylase\> 1.5 x ULN but no clinical or imaging confirmed pancreatitis can be included in the group. Alkaline phosphatase (ALP)≤2.5ULN, subjects with bone metastases, ALP≤5ULN; 9. Non-surgically sterilized female subjects of childbearing age must have a negative serum HCG test within 3 days before the first medication, and non-lactating period. Male subjects and females of childbearing age must start the first study drug to after the last study drug 6 contraception within months; 10. Subjects voluntarily join the study, with good compliance, with safety and survival follow-up.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase Ⅰb: Determination of Recommended Phase II dose (RP2D) of Escalating Dose of Fluzoparib with Apatinib | Up to 28 days after the first dose of Fluzoparib and Apatinib combination therapy | The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for the dose expansion arms, based on safety, tolerability and efficacy data collected during the dose escalation portion of the study |
| PhaseⅠb: Incidence of Adverse Events [safety and tolerability] | From screening up to 28 days after end of treatment | Adverse events defined according to Common Terminology for Adverse Events (CTCAE) v5.0 |
| Phase Ⅱ: Objective Response Rate(ORR) as Assessed by the Investigator according to RECIST v1.1 | up to approximately 2 Years | Objective Response Rate(Complete response + Partial response (CR+PR)), determined using RECIST v1.1 criteria, defined as best overall response (complete or partial response) across all assessment time points. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Event Rate（AER） | Up to approximately 2 Years | Adverse events defined according to Common Terminology for Adverse Events (CTCAE) v5.0 |
| Progression Free Survival（PFS） | Up to approximately 2 Years | Progression Free Survival, defined as first assessment of disease progression or death, whichever is earlier. |
| Biomarker Detection | Up to approximately 2 Years | Evaluation of TP53 gene status through next-generation sequencing technology |
| Overall survival（OS） | Up to approximately 2 Years | Overall survival is the time from intervention to death due to any reason or lost of follow-up |
| Duration of Response（DoR） | Up to approximately 2 Years | Duration of Response, determined using RECIST v1.1 criteria. |
Countries
China
Contacts
Primary ContactHaitao Wang, MD
Backup ContactLi Zang, MD
Outcome results
None listed