Trial Title:
Safety and Tolerability of LDRT+Sugemalimab+Chemotherapy+Olaparib for First-Line Treatment of SLFN-11 Positive ES-SCLC
NCT ID:
NCT06217757
Condition:
Lung Cancer
Extensive-stage Small-cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Etoposide
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:
Radiation
Intervention name:
Low-dose radiotherapy
Description:
The LDRT deals with primary tumour in a 15 Gy of 5fractions over five days, starting from
Day 1 in the first cycle.
Arm group label:
Low-dose radiotherapy combined with sugemalimab, olaparib, etoposide and cisplatin
Other name:
LDRT
Intervention type:
Drug
Intervention name:
Etoposide
Description:
Etoposide will be administered intravenously at a dose of 100 mg/m^2 on Days 1, 2 and 3
of each 21-day cycle during the induction phase (Cycles 1-4).
Arm group label:
Low-dose radiotherapy combined with sugemalimab, olaparib, etoposide and cisplatin
Other name:
One of the standard chemotherapy regimens
Intervention type:
Drug
Intervention name:
Cisplatin
Description:
Cisplatin will be administered as intravenous infusion at a dose of 25 mg/m^2 on Days 1,
2 and 3 of each 21-day cycle during the induction phase (Cycles 1-4).
Arm group label:
Low-dose radiotherapy combined with sugemalimab, olaparib, etoposide and cisplatin
Other name:
One of the standard chemotherapy regimens
Intervention type:
Drug
Intervention name:
Sugemalimab
Description:
Sugemalimab will be administered by intravenous infusion at a dose of 1200mg on Day 1 of
each 21-day cycle for a maximum of 2 years or progressive disease or intolerable
toxicity.
Arm group label:
Low-dose radiotherapy combined with sugemalimab, olaparib, etoposide and cisplatin
Other name:
Programmed Death Ligand-1 (PD-L1) Inhibitor
Intervention type:
Drug
Intervention name:
Olaparib
Description:
Olaparib will be administered orally at a dose of 150mg qod Day 1,3,5,7 or 150 mg qd/150
mg bid/300mg in the morning and 150mg in the evening/300 mg bid on Day 1-7 of each 21-day
cycle for a maximum of 2 years or progressive disease or intolerable toxicity.
Arm group label:
Low-dose radiotherapy combined with sugemalimab, olaparib, etoposide and cisplatin
Other name:
poly ADP-ribose polymerase (PARP) inhibitor
Summary:
The purpose of this study was to evaluate the safety and efficacy of low-dose
radiotherapy (LDRT) combined with sugemalimab, olaparib, chemotherapy in the first-line
treatment of SLFN-11 positive extensive stage small cell lung cancer.
Detailed description:
This study consists of dose escalation and dose expansion in China. Subjects who fulfil
all the inclusion criteria and none of the exclusion criteria will be enrolled and
receive treatment with Sugemalimab, Etoposide/Cisplatin Chemotherapy and Olaparib for 4
cycles with LDRT in the first cycle. Sugemalimab in combination with olaparib will be
administered for maintenance therapy after 4 cycles. Sugemalimab will be administered at
a dose of 1200 mg every 3 weeks (Q3W) in the first day of every cycle. The LDRT deals
with primary tumour in a 15 Gy of 5 fractions over five days, starting from day 1 in the
first cycle. Dose of olaparib will identify by assessed recommended dose for expansion
(RDE) in dose escalation stage.A dose expansion stage will be conducted after dose
escalation. The primary endpoint is safety.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Men or women aged more than or equal to (≥) 18 years old and less than or equal to
(≤) 75 years old
2. Histologically or cytologically confirmed ES-SCLC
3. No prior treatment for ES-SCLC
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
5. Five white slides (unstained paraffin sections) were available for
immunohistochemical SLFN-11 detection and SLFN-11 was positive
6. Extensive clinical stage. American Joint Committee on Cancer (AJCC) 8th edition
Stage IV with lesions exceeding one side of the chest and including malignant
pleural and pericardial effusions or hematogenous metastases (any T, any N,
M1a/b/c); or T3-4 due to multiple nodules in the lung or tumor/nodule size too large
to be included in a T3-4 disease within a tolerable radiotherapy schedule
7. The subjects were considered suitable for combining etoposide with cisplatin
chemotherapy and low-dose radiotherapy as first-line treatment for extensive -stage
small cell lung cancer
8. Have measurable lesions as defined by RECIST1.1, with at least one lesion (never
previously treated with radiation) of ≥10 mm longest diameter accurately measured by
computed tomography (CT) or magnetic resonance imaging (MRI) at baseline (except for
lymph nodes, which must have a short axis of ≥15 mm) and the lesion is suitable for
repeat and accurate measurements
9. Patients with brain metastases must be asymptomatic or stable on steroids and
anticonvulsants for at least 1 month prior to study treatment. Participants with
suspected brain metastases during screening should have a CT/MRI of the brain prior
to study
10. No previous treatment with immune checkpoint inhibitors and PARP inhibitors,
including but not limited to other anti-PD-1, anti-PD-L1 and anti-programmed cell
death ligand 2 (anti-PD-L2) antibodies, with the exception of therapeutic anti-tumor
vaccines. No prior chemotherapy or radiation therapy to the chest lesion
11. Weight over 30 Kg
12. Life expectancy ≥ 12 weeks
13. Have adequate organ and bone marrow functional reserve and normal major organ
function
14. Patients were compliant, voluntarily enrolled in the study and signed an informed
consent form
15. For women or men with childbearing potential: use effective contraception to avoid
conception or embryonic drug exposure during treatment and for 5 months after the
last dose of sugemalimab and for 6 months after the last dose of cisplatin or
etoposide. Female subjects are prohibited from donating eggs during this period and
males are prohibited from donating sperm during this period
Exclusion Criteria:
1. Histopathologic or cytopathologic diagnosis of mixed small cell lung cancer or
non-small cell lung cancer
2. Limited stage small cell lung cancer
3. Combination of poorly controlled malignant pleural or pericardial effusions
requiring continuous drainage
4. Presence of active or symptomatic brain metastases or Leptomeningeal metastases
5. Prior systemic antitumor therapy (chemotherapy, targeted agents such as PARP
inhibitors) or immune checkpoint inhibitors for SCLC
6. Presence of active, unstable systemic disease such as active infection, autoimmune
disease, inflammatory disease (uncontrolled hypertension, heart failure (NYHA
classification >= Class II), unstable angina, acute coronary syndrome, severe
arrhythmia, severe hepatic, renal or metabolic disease, human immunodeficiency virus
(HIV) immunodeficiency virus (HIV) infected patients
7. Previous allogeneic stem cell or solid organ transplantation
8. Patients with prior interstitial lung disease, drug-induced interstitial lung
disease, or active interstitial pneumonia requiring systemic glucocorticoid or
immunosuppressive therapy; Patients with pulmonary interstitial fibrosis or active
pulmonary tuberculosis
9. Severe infection within 4 weeks prior to the start of study treatment, including but
not limited to hospitalization for infection, bacteremia, or severe pneumonia
10. Received therapeutic oral or intravenous infusion of antibiotics within 2 weeks
prior to the start of study treatment
11. Been diagnosed or treated for another malignancy (excluding resected basal cell
carcinoma of the skin or other carcinoma in situ) within 5 years prior to
randomization to this study
12. For pregnant or lactating females or male or female subjects of reproductive
potential who refuse to use effective contraception during treatment and within 5
months of the last dose of sugemalimab and within 6 months of the last dose of
cisplatin or etoposide
13. Allergic to the study drug or its components
14. The investigator believes that the patients may not be able to complete the study or
comply with the requirements of the study
15. Inadequate bone marrow function and vital organ function reserve
16. Concurrent participation in another clinical study, unless it is an observational
(non-interventional) clinical study or a follow-up phase of an interventional study,
excluding patients who have received any other experimental drug within 28 days
prior to the start of study treatment
17. Patients who are not suitable for etoposide-cisplatin chemotherapy, sugemalimab or
olaparib
18. History of thoracic radiotherapy or plan to receive intensive thoracic radiotherapy
prior to systemic therapy. External chest radiotherapy for palliative purposes
(e.g., bone metastases) is allowed, but must be completed prior to the first
administration of study drug
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
West China Hospital of Sichuan University
Address:
City:
Chengdu
Zip:
610044
Country:
China
Status:
Recruiting
Contact:
Last name:
You Lu
Phone:
+8602885423571
Email:
radyoulu@hotmali.com
Contact backup:
Last name:
Min Yu
Phone:
+8602885423571
Email:
yuminisagoodgirl@163.com
Investigator:
Last name:
You Lu, MD
Email:
Principal Investigator
Investigator:
Last name:
Min Yu, MD
Email:
Sub-Investigator
Start date:
April 18, 2024
Completion date:
March 20, 2027
Lead sponsor:
Agency:
Sichuan University
Agency class:
Other
Source:
Sichuan University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06217757
