Trial Title:
Study of Selinexor Combined With Olaparib in Relapsed/Refractory Extensive Stage Small Cell Lung Cancer
NCT ID:
NCT05975944
Condition:
Extensive-stage Small Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Olaparib
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Selinexor，Olaparib
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.
Arm group label:
dose-escalation part of phase Ib clinical trial
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.
Criteria for 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Tianjin Medical University Cancer Institute and Hospital
Address:
City:
Tianjin
Zip:
300060
Country:
China
Status:
Recruiting
Contact:
Last name:
Huang Ding Zhi, PHD
Start date:
September 2023
Completion date:
May 2024
Lead sponsor:
Agency:
Tianjin Medical University Cancer Institute and Hospital
Agency class:
Other
Source:
Tianjin Medical University Cancer Institute and Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05975944
