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Study of Selinexor Combined With Olaparib in Relapsed/Refractory Extensive Stage Small Cell Lung Cancer

Primary Purpose

Extensive-stage Small Cell Lung Cancer

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Selinexor,Olaparib
Sponsored by
Tianjin Medical University Cancer Institute and Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Extensive-stage Small Cell Lung Cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: The diagnosis of SCLC is confirmed by histology or cytology, and according to VALSG and AJCC8, the imaging diagnosis is extensive stage. The condition progresses after receiving at least 1 line of treatment, and within 6 months after the last treatment. The expected survival time is not less than 12 weeks. According to RECIST V1.1, there is at least one measurable lesion that has not undergone radiation therapy. The Eastern Cooperative Oncology Group (ECOG) physical condition score is evaluated as 0 or 1. When screening, there is sufficient bone marrow reserve, and no blood transfusion or hematopoietic stimulating factor treatment has been received 10 days before the test. The definition is as follows: absolute neutrophil counts (ANC) ≥ 1.5×109/L, platelet (PLT) ≥ 100×109/L and hemoglobin (HGB) ≥ 90g/L. Appropriate organ function during screening, meeting the following criteria: aspartate aminotransferase (AST) ≤ 2.5×ULN (with liver metastasis ≤ 5×ULN); alanine aminotransferase (ALT) ≤ 2.5ULN (with liver metastasis ≤ 5ULN); total serum bilirubin ≤ 1.5×ULN (with tumor infiltration ≤ 3×ULN); serum creatinine (Scr) ≤ 1.5×ULN, or creatinine clearance rate ≥ 60mL/min; international normalized ratio (INR) ≤ 1.5×ULN, and activated partial thromboplastin time (APTT) ≤ 1.5×ULN; the urine pregnancy test for women of childbearing age needs to be negative, and any male and female patients with fertility must agree to use effective contraceptive methods throughout the entire study process and for at least 1 year after treatment. Exclusion Criteria: During screening, patients with symptomatic central nervous system (CNS) metastasis (asymptomatic CNS metastasis, or asymptomatic and stable condition after local treatment for 4 weeks can be enrolled). Individuals with a history of central nervous system diseases before screening, such as epilepsy, cerebral ischemia/bleeding, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, mental illness, or any autoimmune disease associated with central nervous system involvement. Received chemotherapy, radiation therapy, immunotherapy, targeted therapy, biological therapy, endocrine therapy within 4 weeks of screening, and was evaluated by the researcher as not suitable for enrollment. The adverse reactions of previous anti-tumor treatments have not yet recovered to level 1 (CTCAE5.0), except for toxicity that the researchers have determined to have no safety risk, such as hair loss and level 2 peripheral neurotoxicity. Those who discontinue systemic hormone therapy for less than 72 hours before the first administration, but are allowed to use physiological replacement doses of hormones (such as prednisone < 10mg/d or equivalent). Received organ/tissue transplantation before screening. Prior to screening, it was known that the patient had active systemic autoimmune diseases and was currently undergoing treatment. Those who meet any of the following conditions during screening: hepatitis B surface antigen (HBsAg) is positive, and the copy number of HBV DNA is greater than the measurable lower limit; hepatitis C antibody (HCV Ab) is positive; treponema pallidum antibody (TP-Ab) is positive; HIV antibody is positive; The copy numbers of EBV-DNA and CMV-DNA are higher than the measurable lower limit. Individuals who have undergone major surgery or experienced significant trauma within 4 weeks prior to screening, or who require elective surgery during the trial period, have been evaluated by the researchers as unsuitable for inclusion. Within 2 years prior to screening or currently suffering from other malignant tumors. When screening, the heart meets any of the following conditions: New York Heart Association (NYHA) ≥ Level II, Left Ventricular Ejection Fraction (LVEF) ≤ 50% (ECHO); Hypertension (systolic blood pressure ≥ 140mmHg and/or diastolic blood pressure ≥ 90mmHg) or pulmonary hypertension that has not been controlled after standardized treatment; Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other Grade 3 or higher cardiovascular and cerebrovascular events occurred within 6 months before the first administration; valvular disease with clinical significance; There are serious cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias that require clinical intervention, II-III degree atrioventricular block, etc. Patients with tumor involving the atrium or ventricle during screening. When screening, there are clinical emergencies that require urgent treatment due to tumor obstruction or compression (such as intestinal obstruction or vascular compression). Individuals with active bleeding during screening. Those with a history of deep vein thrombosis or pulmonary embolism within 6 months before screening. Individuals who have received live vaccines within 6 weeks before screening. Subjects with uncontrolled systemic bacterial, viral, or fungal infections after optimal treatment. Participated in other interventional clinical studies within 4 weeks before the first administration. Individuals with poor adherence or those who are deemed unsuitable for clinical trials by researchers due to other reasons.

Sites / Locations

  • Tianjin Medical University Cancer Institute and HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

dose-escalation part of phase Ib clinical trial

Arm Description

Dose level 1: Selinexor 40mg PO QW, Olaparib 150mg PO BID; Dose level 2: Selinexor 60mg PO QW, Olaparib 150mg PO BID; Dose level 3: Selinexor 80mg PO QW, Olaparib 150mg PO BID.

Outcomes

Primary Outcome Measures

MTD
MTD
ORR
ORR

Secondary Outcome Measures

DCR
DCR
PFS
PFS
OS
OS

Full Information

First Posted
May 28, 2023
Last Updated
July 27, 2023
Sponsor
Tianjin Medical University Cancer Institute and Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05975944
Brief Title
Study of Selinexor Combined With Olaparib in Relapsed/Refractory Extensive Stage Small Cell Lung Cancer
Official Title
A Phase Ib/II Clinical Study Evaluating the Safety, Tolerability, and Efficacy of Selinexor Combined With Olaparib in the Treatment of Recurrent/Refractory Extensive-stage Small Cell Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 2023 (Anticipated)
Primary Completion Date
September 2023 (Anticipated)
Study Completion Date
May 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tianjin Medical University Cancer Institute and Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study is a multicenter, single arm, open, non-randomized, dose-escalation/ expansion phase Ib/II clinical study. The dose-escalation part of phase Ib clinical trial was conducted according to the Bayesian Optimal Interval Design (BOIN), with a total of three dose groups: low, medium, and high. Dose level 1: Selinexor 40mg PO QW, Olaparib 150mg PO BID; Dose level 2: Selinexor 60mg PO QW, Olaparib 150mg PO BID; Dose level 3: Selinexor 80mg PO QW, Olaparib 150mg PO BID. The number of patients in each group is 3, with a maximum sample size of 9, to evaluate the safety and effectiveness of the medication, and to provide a basis for recommended phase II dose (RP2D). Eligible subjects received medication on the first day and then entered a 21 day observation period of dose-limiting toxicity (DLT). DLT is defined as the occurrence of level 3 non hematological toxicity or level 4 hematological toxicity. Evaluate the efficacy every 6 weeks. In this study, an independent Data Safety Monitoring Committee (DSMC) and an Independent Review Committee (IRC) were established to regularly review the safety and effectiveness data of each research center, with the aim of protecting subjects safety, ensuring the reliability of clinical trials and the objectivity of trial results.
Detailed Description
This study is a multicenter, single arm, open, non-randomized, dose-escalation/ expansion phase Ib/II clinical study. The dose-escalation part of phase Ib clinical trial was conducted according to the Bayesian Optimal Interval Design (BOIN), with a total of three dose groups: low, medium, and high. Dose level 1: Selinexor 40mg PO QW, Olaparib 150mg PO BID; Dose level 2: Selinexor 60mg PO QW, Olaparib 150mg PO BID; Dose level 3: Selinexor 80mg PO QW, Olaparib 150mg PO BID. The number of patients in each group is 3, with a maximum sample size of 9, to evaluate the safety and effectiveness of the medication, and to provide a basis for recommended phase II dose (RP2D). Eligible subjects received medication on the first day and then entered a 21 day observation period of dose-limiting toxicity (DLT). DLT is defined as the occurrence of level 3 non hematological toxicity or level 4 hematological toxicity. Evaluate the efficacy every 6 weeks. In this study, an independent Data Safety Monitoring Committee (DSMC) and an Independent Review Committee (IRC) were established to regularly review the safety and effectiveness data of each research center, with the aim of protecting subjects safety, ensuring the reliability of clinical trials and the objectivity of trial results.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Extensive-stage Small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
49 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
dose-escalation part of phase Ib clinical trial
Arm Type
Experimental
Arm Description
Dose level 1: Selinexor 40mg PO QW, Olaparib 150mg PO BID; Dose level 2: Selinexor 60mg PO QW, Olaparib 150mg PO BID; Dose level 3: Selinexor 80mg PO QW, Olaparib 150mg PO BID.
Intervention Type
Drug
Intervention Name(s)
Selinexor,Olaparib
Intervention Description
Dose level 1: Selinexor 40mg PO QW, Olaparib 150mg PO BID; Dose level 2: Selinexor 60mg PO QW, Olaparib 150mg PO BID; Dose level 3: Selinexor 80mg PO QW, Olaparib 150mg PO BID.
Primary Outcome Measure Information:
Title
MTD
Description
MTD
Time Frame
through study completion, an average of 1 year
Title
ORR
Description
ORR
Time Frame
through study completion, an average of 1 year
Secondary Outcome Measure Information:
Title
DCR
Description
DCR
Time Frame
through study completion, an average of 1 year
Title
PFS
Description
PFS
Time Frame
through study completion, an average of 1 year
Title
OS
Description
OS
Time Frame
through study completion, an average of 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: The diagnosis of SCLC is confirmed by histology or cytology, and according to VALSG and AJCC8, the imaging diagnosis is extensive stage. The condition progresses after receiving at least 1 line of treatment, and within 6 months after the last treatment. The expected survival time is not less than 12 weeks. According to RECIST V1.1, there is at least one measurable lesion that has not undergone radiation therapy. The Eastern Cooperative Oncology Group (ECOG) physical condition score is evaluated as 0 or 1. When screening, there is sufficient bone marrow reserve, and no blood transfusion or hematopoietic stimulating factor treatment has been received 10 days before the test. The definition is as follows: absolute neutrophil counts (ANC) ≥ 1.5×109/L, platelet (PLT) ≥ 100×109/L and hemoglobin (HGB) ≥ 90g/L. Appropriate organ function during screening, meeting the following criteria: aspartate aminotransferase (AST) ≤ 2.5×ULN (with liver metastasis ≤ 5×ULN); alanine aminotransferase (ALT) ≤ 2.5ULN (with liver metastasis ≤ 5ULN); total serum bilirubin ≤ 1.5×ULN (with tumor infiltration ≤ 3×ULN); serum creatinine (Scr) ≤ 1.5×ULN, or creatinine clearance rate ≥ 60mL/min; international normalized ratio (INR) ≤ 1.5×ULN, and activated partial thromboplastin time (APTT) ≤ 1.5×ULN; the urine pregnancy test for women of childbearing age needs to be negative, and any male and female patients with fertility must agree to use effective contraceptive methods throughout the entire study process and for at least 1 year after treatment. Exclusion Criteria: During screening, patients with symptomatic central nervous system (CNS) metastasis (asymptomatic CNS metastasis, or asymptomatic and stable condition after local treatment for 4 weeks can be enrolled). Individuals with a history of central nervous system diseases before screening, such as epilepsy, cerebral ischemia/bleeding, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, mental illness, or any autoimmune disease associated with central nervous system involvement. Received chemotherapy, radiation therapy, immunotherapy, targeted therapy, biological therapy, endocrine therapy within 4 weeks of screening, and was evaluated by the researcher as not suitable for enrollment. The adverse reactions of previous anti-tumor treatments have not yet recovered to level 1 (CTCAE5.0), except for toxicity that the researchers have determined to have no safety risk, such as hair loss and level 2 peripheral neurotoxicity. Those who discontinue systemic hormone therapy for less than 72 hours before the first administration, but are allowed to use physiological replacement doses of hormones (such as prednisone < 10mg/d or equivalent). Received organ/tissue transplantation before screening. Prior to screening, it was known that the patient had active systemic autoimmune diseases and was currently undergoing treatment. Those who meet any of the following conditions during screening: hepatitis B surface antigen (HBsAg) is positive, and the copy number of HBV DNA is greater than the measurable lower limit; hepatitis C antibody (HCV Ab) is positive; treponema pallidum antibody (TP-Ab) is positive; HIV antibody is positive; The copy numbers of EBV-DNA and CMV-DNA are higher than the measurable lower limit. Individuals who have undergone major surgery or experienced significant trauma within 4 weeks prior to screening, or who require elective surgery during the trial period, have been evaluated by the researchers as unsuitable for inclusion. Within 2 years prior to screening or currently suffering from other malignant tumors. When screening, the heart meets any of the following conditions: New York Heart Association (NYHA) ≥ Level II, Left Ventricular Ejection Fraction (LVEF) ≤ 50% (ECHO); Hypertension (systolic blood pressure ≥ 140mmHg and/or diastolic blood pressure ≥ 90mmHg) or pulmonary hypertension that has not been controlled after standardized treatment; Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other Grade 3 or higher cardiovascular and cerebrovascular events occurred within 6 months before the first administration; valvular disease with clinical significance; There are serious cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias that require clinical intervention, II-III degree atrioventricular block, etc. Patients with tumor involving the atrium or ventricle during screening. When screening, there are clinical emergencies that require urgent treatment due to tumor obstruction or compression (such as intestinal obstruction or vascular compression). Individuals with active bleeding during screening. Those with a history of deep vein thrombosis or pulmonary embolism within 6 months before screening. Individuals who have received live vaccines within 6 weeks before screening. Subjects with uncontrolled systemic bacterial, viral, or fungal infections after optimal treatment. Participated in other interventional clinical studies within 4 weeks before the first administration. Individuals with poor adherence or those who are deemed unsuitable for clinical trials by researchers due to other reasons.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
huang ding zhi, M.D.
Phone
+86-22-23340123-3200
Email
dingzhih72@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
huang ding zhi, M.D.
Email
dingzhih72@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
huang ding zhi, M.D.
Organizational Affiliation
Tianjin Medical University Cancer Institute and Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tianjin Medical University Cancer Institute and Hospital
City
Tianjin
ZIP/Postal Code
300060
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Huang Ding Zhi, PHD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified individul participant data for all primary and secondary outcome measures will be made available.
IPD Sharing Time Frame
Data will be available within 6 months of study completion
IPD Sharing Access Criteria
Data access requests will be reviewed by an external indepentent Review Panel. Requesdtors will be required to sign a Data Access Agreement.
IPD Sharing URL
http://www.cttq.com/
Citations:
PubMed Identifier
33493586
Citation
Wang J, Sun T, Meng Z, Wang L, Li M, Chen J, Qin T, Yu J, Zhang M, Bie Z, Dong Z, Jiang X, Lin L, Zhang C, Liu Z, Jiang R, Yang G, Li L, Zhang Y, Huang D. XPO1 inhibition synergizes with PARP1 inhibition in small cell lung cancer by targeting nuclear transport of FOXO3a. Cancer Lett. 2021 Apr 10;503:197-212. doi: 10.1016/j.canlet.2021.01.008. Epub 2021 Jan 23.
Results Reference
result

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Study of Selinexor Combined With Olaparib in Relapsed/Refractory Extensive Stage Small Cell Lung Cancer

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