Trial Title:
Study of Polymeric Micellar Paclitaxel, Platinum Combined With Sindilizumab Injection for Advanced Non-squamous NSCLC
NCT ID:
NCT05782426
Condition:
Non-squamous NSCLC
Conditions: Official terms:
Carcinoma, Non-Small-Cell Lung
Paclitaxel
Conditions: Keywords:
NSCLC
paclitaxel polymeric micelles for injection
sindilizumab injection
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Patients will be treated with paclitaxel polymeric micelles for injection, platinum
(cisplatin/carboplatin) in combination with sindilizumab for 4-6 cycles. If patient
assessment is of clinical benefit, maintenance therapy with sindilizumab plus paclitaxel
polymeric micelles for injection(≤230mg/m^2) can be continued based on investor's
evaluation and patient's own choice until disease progression (PD), unacceptable
toxicity, withdrawal of consent, initiation of additional antineoplastic therapy, death,
or other protocol-specified conditions for discontinuation of treatment, whichever comes
first.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
paclitaxel polymeric micelles for injection
Description:
Patients will be treated with paclitaxel polymeric micelles for injection, platinum
(cisplatin/carboplatin) in combination with sindilizumab for 4-6 cycles. If patient
assessment is of clinical benefit, maintenance therapy with sindilizumab plus paclitaxel
polymeric micelles for injection(≤230mg/m^2) can be continued based on investor's
evaluation and patient's own choice until disease progression (PD), unacceptable
toxicity, withdrawal of consent, initiation of additional antineoplastic therapy, death,
or other protocol-specified conditions for discontinuation of treatment, whichever comes
first.
Arm group label:
paclitaxel polymeric micelles for injection, platinum combined with sindilizumab injection
Other name:
platinum
Other name:
sindilizumab injection
Summary:
This is a prospective, single-arm, single-center, phaseⅡtrial to evaluate the efficacy
and safety of Paclitaxel Polymeric Micelles for Injection, platinum
(cisplatin/carboplatin) in combination with sindilizumab injection as first-line
chemotherapy in advanced or metastatic non-squamous NSCLC patients without EGFR mutation
or ALK rearrangement.
Detailed description:
Patients with histologically or cytologically confirmed metastatic or recurrent stage
ⅢB/Ⅳ non-squamous NSCLC, inoperable or inappropriate for radical concurrent
chemoradiotherapy, and without previous systemic treatment will be screened after signing
Informed Consent. Patients will be treated with paclitaxel polymeric micelles for
injection, platinum (cisplatin/carboplatin) in combination with sindilizumab for 4-6
cycles. If patient assessment is of clinical benefit, maintenance therapy with
sindilizumab plus paclitaxel polymeric micelles for injection (≤230mg/m^2) can be
continued based on investor's evaluation and patient's own choice until disease
progression (PD), unacceptable toxicity, withdrawal of consent, initiation of additional
antineoplastic therapy, death, or other protocol-specified conditions for discontinuation
of treatment, whichever comes first.
Patients receiving sindilizumab who has first radiologic evidence of PD according to
RECIST 1.1 can continue the treatment if their clinical status is stable, without
evidence of rapid radiologic progression and if they are deemed by the investigator to be
continuing to benefit from the treatment. Re-evaluation by imaging is required after a
minimum interval of 4 weeks (±7 days), if PD is confirmed by the re-evaluation, the study
treatment should be stopped. If PD is not confirmed, the study treatment can be
continued, with assessments at the planned time points for imaging as specified in the
protocol, until PD is confirmed on imaging.
The maximum treatment duration of sindilizumab injection and paclitaxel polymeric
micelles for injection is 24 months.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Written informed consent must be signed before implementing any trial-related
procedures;
2. Age ≥18 years old;
3. Patients with histologically or cytologically confirmed metastatic or recurrent
(stage IIIB/IV) non-squamous NSCLC (International Association for the Study of Lung
Cancer and American Joint Committee on Classification of Cancer, 8th Edition TNM
staging), inoperable or inappropriate for radical concurrent chemoradiotherapy, and
without previous systemic treatment；
4. No EGFR gene sensitive mutation or ALK gene fusion mutation is confirmed by
histological specimens; PD-L1 immunohistochemical results is required before
enrollment; There is no special restriction on the source of genetic test report.
5. According to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1),
there is at least one radiographically measurable lesion. Lesions located in the
area of previous radiotherapy can be considered as measurable lesions if the
progression is confirmed.
6. Have not received any previous systemic antitumor therapy for advanced/metastatic
diseases. Participants who have previously received platinum-based
adjuvant/neoadjuvant chemotherapy, or radical chemoradiotherapy for advanced disease
are allowed to enroll if the interval between disease progression or recurrence and
the end of the last chemotherapy treatment is at least 6 months.
7. Patients are allowed to receive palliative radiotherapy provided that it is
completed 7 days before the first study treatment and the radiotherapy-related
toxicity have recovered to grade 1 or less (CTCAE5.0);
8. ECOG score: 0-1
9. Expected survival time > 3 months
10. Normal organ function, patients should meet the following laboratory indicators:
1)Blood routine test should meet the following criteria (no blood transfusion, no use of
blood products, granulocyte colony-stimulating factor, or other hematopoietic growth
factors within 7 days before blood routine test); White blood cell count ≥3.0x10^9/L,
absolute neutrophil count (ANC) ≥1.5x10^9/L，Platelet count ≥100×10^9/L，Hemoglobin >9g/dL.
If patients receive blood component transfusion (red blood cells, platelets, etc.) during
the screening period, blood routine test should be performed again at an interval of 1
week to meet the above criteria before continuing screening.
2) Blood biochemical examination must meet the following criteria: Total bilirubin ≤1.5
times the upper limit of normal (ULN), and aspartate aminotransferase (AST), alanine
aminotransferase (ALT), or alkaline phosphatase (ALP) ≤2.5 times ULN (ALT, AST, or
ALP≤ 5×ULN for patients with liver metastases, and ALP≤10×ULN for patients with bone
metastases); Serum creatinine ≤1.5 times ULN and creatinine clearance (calculated
using Cockcroft-Gault formula) ≥60 ml/min； 3) Normal coagulation function, defined
as international normalized ratio (INR) or prothrombin time (PT) ≤1.5 times ULN; 4)
Normal thyroid function, defined as thyroid stimulating hormone (TSH) within the
normal range. Subjects with baseline TSH beyond the normal range, but total T3 (or
FT3) and FT4 are within the normal range can also be enrolled; 5) Myocardial
zymogram within the normal range (if the investor judges that the simple laboratory
result is not of clinical significance, the patient is allowed to be included);
11.For female patients of childbearing age, a negative urine or serum pregnancy test
should be performed within 3 days before the first study drug administration (day 1
of cycle 1). If the urine pregnancy test result cannot be confirmed as negative, a
blood pregnancy test is requested. Female patients who are not of childbearing age
are defined as those who have been postmenopausal for at least 1 year or have
undergone surgical sterilization or hysterectomy; 12.If there is a risk of
conception, all patients (male or female) are required to use contraception
throughout the treatment period until 180 days after the last study drug
administration.
Exclusion Criteria:
1. Patients with small cell lung cancer (SCLC, including SCLC mixed with NSCLC),
squamous non-small cell lung cancer; Non-squamous NSCLC with EGFR gene sensitive
mutation and ALK gene fusion mutation;
2. Patients who have received radiation therapy before the first administration of
study drug, and if one of the following conditions occurred:
1) ≥30% of bone marrow have received radiotherapy within 14 days prior to treatment; 2)
Radiation to a lung lesion at a dose of >30Gy within 6 weeks before treatment( to be
eligible, patients must have recovered to grade 1 or lower from previous radiation
toxicity, no need for glucocorticoids, and no history of radiation pneumonitis);
3)Palliative radiation therapy completed within 7 days before the first study drug
administration.
3.Malignant diseases other than NSCLC diagnosed within 5 years before the first dose
(excluding radical basal cell carcinoma, squamous carcinoma, and/or radical resection
carcinoma in situ); 4.Currently participating in an interventional clinical study
treatment, or receiving other study drugs or using study devices within 4 weeks before
the first dose； 5.Previous treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or
agent targeting another stimulatory or synergistic T-cell receptor (e.g., CTLA-4, OX-40,
CD137)； 6.Received systemic treatment with Chinese drugs or immunomodulatory drugs
(including thymosin, interferon and interleukin, except for local use to control pleural
effusion) with anti-NSCLC indications within 2 weeks before the first dose; 7.An active
autoimmune disease requiring systemic therapy (e.g., disease-modifying agents,
glucocorticoids, or immunosuppressants) occurred within 2 years before the first dose.
Alternative therapies (e.g., thyroxine, insulin, or physiological glucocorticoids for
adrenal or pituitary insufficiency) is not considered systemic therapy; 8.Receiving
systemic glucocorticoid therapies (excluding topical glucocorticoids by nasal spray,
inhalation, or other route)) or any other form of immunosuppressive therapies within 7
days before the first medication of the study; Note: Physiological doses of
glucocorticoids (≤10 mg prednisone/day or equivalent) are permitted； 9.Patients with
active or untreated central nervous system (CNS) metastasis;
1. If the patient's CNS tumor metastasis is confined to supratentorial and/or
cerebellum, has been adequately treated, and has been clinically stable (imaging
testing, enhanced MRI or CT is preferred) for at least 4 weeks, Participants are
eligible for the study if they have recovered to NCI-CTC AE ≤ grade1 at least 2
weeks before the first dose of medication. If new asymptomatic CNS metastases are
detected on screening scans, radiation therapy and/or surgery for CNS metastases are
required;
2. Glucocorticoid therapy is not required, or glucocorticoid therapy is discontinued
within 7 days before the first dose, or glucocorticoid dosage is stable and reduced
to less than 10mg prednisone per day (or equivalent) within 7 days before the first
dose.
10.Spinal cord compression without radical treatment with surgery and/or radiotherapy, or
previously diagnosed spinal cord compression without clinical evidence of stable disease
for ≥4 weeks before enrollment; 11.Patients with clinically uncontrollable pleural
effusion/peritoneal effusion (patients who did not need to drain effusion or stopped
drainage for 3 days without significant increase in effusion could be enrolled); 12.Known
allogeneic organ transplantation (except corneal transplantation) or allogeneic
hematopoietic stem cell transplantation; 13.Patients with known allergies to
sindilizumab, paclitaxel polymeric micelles for injection, platinum
(cisplatin/carboplatin) and other active ingredients or excipients; 14.Patients who have
not fully recovered from any intervention-related toxicity and/or complications before
starting treatment (i.e., grade ≤1 or baseline, excluding fatigue or alopecia);
15.Patient with a history of human immunodeficiency virus (HIV) infection (i.e., HIV 1/2
antibody positive); 16.Patient who has untreated active hepatitis B (defined as both
HBsAg positivity and HBV-DNA copies greater than the upper limit of normal range in the
laboratory of the participating center);
Note: Patient with hepatitis B who meets the following criteria are also eligible for
inclusion:
1. Patients with HBV viral load <1000 copies /ml (200 IU/ml) before the first study
medication should receive anti-HBV therapy throughout the study chemotherapy to
avoid viral reactivation;
2. For patients with anti-HBc (+), HBsAg (-), anti-hbs (-) and HBV viral load (-),
prophylactic anti-HBV therapy is not required, but viral reactivation should be
closely monitored.
17.Active HCV-infected patients (positive for HCV antibodies and HCV-RNA levels above the
upper limit of detection); 18.Patients who have received a live vaccine within 30 days
before the first dose of study drug (cycle 1, day 1); Note: Administration of injectable
inactivated virus vaccine against seasonal influenza within 30 days before the first dose
of study is allowed; Live, attenuated, intranasal influenza vaccine is not allowed.
19.Pregnant or lactating women; 20.The presence of any serious or uncontrolled systemic
illness, such as:
1）significant rhythm, conduction or morphological abnormalities in resting ECG, such as
complete left bundle branch block, ≥II degree heart block, ventricular arrhythmia or
atrial fibrillation; 2）Unstable angina, congestive heart failure, New York Heart
Association (NYHA) grade ≥ 2 chronic heart failure; 3）Myocardial infarction within 6
months before enrollment; 4）Poor blood pressure control (systolic blood pressure > 140
mmHg, diastolic blood pressure > 90 mmHg)； 5）Patient with a history of noninfectious
pneumonia requiring glucocorticoid treatment within 1 year before the first dose, or
current clinically active interstitial lung disease; 6）Active pulmonary tuberculosis;
7）Presence of active or uncontrolled infection requiring systemic therapy; 8）Presence of
clinically active diverticulitis, abdominal abscess, and gastrointestinal obstruction;
9）Presence of liver diseases such as cirrhosis, decompensated liver disease, acute or
chronic active hepatitis; 10）Poorly controlled diabetes (fasting blood glucose (FBG) >
10mmol/L); 11）Patient whose urine routine test shows urinary protein ≥++ and confirmed
24-hour urinary protein quantitation > 1.0 g; 12）Patients with a mental disorder who is
unable to cooperate with treatment; 21.Patients who have medical history or evidence of
disease, treatment or laboratory abnormalities, or other conditions deemed by the
investigator to be inappropriate for enrollment that may interfere with the results of
the trial or preclude full participation in the study.
-
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Jiangsu Cancer Institute & Hospital
Address:
City:
Nanjing
Zip:
025
Country:
China
Facility:
Name:
Jiangsu Cancer Hospital
Address:
City:
Nanjing
Zip:
210009
Country:
China
Contact:
Last name:
Meiqi Shi
Phone:
13809029766
Email:
shimeiqi1963@163.com
Contact backup:
Last name:
Jifeng Feng
Investigator:
Last name:
Jifeng Feng
Email:
Principal Investigator
Investigator:
Last name:
Meiqi Shi
Email:
Principal Investigator
Investigator:
Last name:
Bo Shen
Email:
Principal Investigator
Start date:
March 15, 2023
Completion date:
January 31, 2026
Lead sponsor:
Agency:
Jiangsu Cancer Institute & Hospital
Agency class:
Other
Source:
Jiangsu Cancer Institute & Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05782426
