Trial Title:
Toripalimab Plus Etoposide and Platinum-based Chemotherapy for Genitourinary Small Cell Carcinoma
NCT ID:
NCT05760053
Condition:
Toripalimab
First-line Treatment
Conditions: Official terms:
Carcinoma
Carcinoma, Small Cell
Small Cell Lung Carcinoma
Cisplatin
Carboplatin
Etoposide
Conditions: Keywords:
Genitourinary small cell carcinoma
Carboplatin
Etoposide
Cisplatin
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
A multicenter, prospective, open label, single-arm, phase II study
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
EP/EC+PD-1
Description:
Toripalimab 240 mg, administered on the first day of each cycle, and a cycle of
administration every 3 weeks. Etoposide 100mg/m2, d1-3, cisplatin 25mg/m2, d1-3 or
carboplatin AUC=5 d1, administered on the first day of each cycle, a cycle of
administration every 3 weeks. Toripalimab combined with etoposide and
cisplatin/carboplatin was used for 4 to 6 courses of treatment.
Arm group label:
EP/EC+PD-1
Other name:
Etoposide, Cisplatin or Carboplatin, plus Toripalimab
Summary:
This study is a prospective, multicenter, open-label, single-arm phase II clinical trial.
A single-arm experimental group of toripalimab, etoposide, and cisplatin/carboplatin was
designed to evaluate its efficacy and safety in small cell carcinoma of the urinary
system.
Detailed description:
This study focuses on patients with locally advanced/metastatic genitourinary small cell
carcinoma (small cell carcinoma originating in the kidney, ureter, bladder, urethra, and
prostate), and it aims to explore the efficacy and safety of toripalimab combined with EP
or EC.
After meeting the enrollment conditions, they received combination therapy: toripalimab
240 mg, administered on the first day of each cycle, and a cycle of administration every
3 weeks. Etoposide 100mg/m2, d1-3, cisplatin 25mg/m2, d1-3 or carboplatin AUC=5 d1,
administered on the first day of each cycle, a cycle of administration every 3 weeks.
Toripalimab combined with etoposide and cisplatin/carboplatin was used for 4 to 6 courses
of treatment. Evaluate the curative effect with imaging every 2 courses. If there is an
opportunity for local treatment after chemotherapy, participate in multidisciplinary
discussions to decide the next step of treatment. For patients who can be treated with
local treatment (surgery, radiotherapy) after treatment, the investigator will receive
maintenance treatment with toripalimab 240 mg/time, every 21 days, until the disease
progresses or unacceptable toxicity occurs. If the curative effect evaluation of the
patient is complete remission (CR), partial remission (PR) or stable disease (SD) after 4
to 6 courses of treatment, maintenance therapy with toripalimab 240mg/time, every 21
days, until the disease progression or intolerable toxicity. The maximum duration of
maintenance treatment is 2 years. Subjects who finished treatment entered the follow-up
period and received safety follow-up and survival follow-up.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Participate voluntarily and sign the informed consent;
2. Age ≥ 18 years old;
3. Life expectancy ≥ 3 months;
4. Physical condition score ECOG 0-2;
5. Pathologically diagnosed as genitourinary small cell carcinoma (recommended central
consultation for difficult pathology), including small cell carcinoma primary in the
kidney, ureter, bladder, urethra, and prostate. The stage is locally advanced or
advanced (stage IIIA or above, that is, cT3 or above N0 M0, or cT1-4a N1-3 M0, or
cT4b any N M0, or any T any N M1), or the investigator judges that local treatment
is not suitable for the time being (surgery, radiotherapy) patients.
6. Patients whose pathology is mixed small cell carcinoma can be included, and the
small cell carcinoma component is ≥50%.
7. Have not received systemic treatment before, or the time interval from the last
adjuvant treatment is more than 6 months;
8. There are measurable or/and evaluable lesions (non-radiotherapy target areas)
(lesion evaluation according to Recist1.1 standard);
9. No serious organ (main organs: heart, lung, liver, kidney) dysfunction (refer to the
respective standards);
10. Blood routine indicators: white blood cell (WBC) ≥ 3 × 109/L; absolute neutrophil
count (ANC) ≥ 1.5 × 109/L; platelet (PLT) ≥ 100 × 109/L; hemoglobin (Hgb) ≥ 8g /dL;
11. Blood biochemical indicators: AST (SGOT), ALT (SGPT) ≤ 2.5 × upper limit of normal
value (ULN) (in the case of no liver invasion) or ≤ 5 × upper limit of normal value
(ULN) (in the case of liver invasion ); total bilirubin (TBIL) ≤ ULN; serum
creatinine clearance calculated according to the CG formula > 30 mL/min
12. Coagulation function: prothrombin time (PT), international normalized ratio (INR) ≤
1.5 × ULN (unless warfarin is being used for anticoagulation);
13. Able to comply with the research visit plan and other program requirements;
14. All patients of childbearing age must agree to take effective contraceptive measures
during the study period and within 6 months of stopping treatment, and the urine
pregnancy test of female patients of childbearing age must be negative before
treatment.
Exclusion Criteria:
1. Received treatment for small cell carcinoma of the urinary system within 2 weeks
before enrollment.
2. Once diagnosed with prostate adenocarcinoma, received endocrine therapy (such as
enzalutamide, apalutamide, abiraterone, etc.) and chemotherapy (docetaxel) for
prostate adenocarcinoma, and is currently considering neuroendocrine differentiation
of prostate cancer.
3. Mixed small cell carcinoma, in which the small cell carcinoma component is less than
50%.
4. Medical history and comorbidities:
(1) Anti-tumor vaccine or cellular immunotherapy has been used before the first dose of
the study drug; (2) Previously received systemic therapy for metastatic lesions; (3) The
patient is participating in other interventional clinical studies or less than 4 weeks
before the end of the previous clinical study; (4) Those who have been less than 4 weeks
away from the last anti-tumor treatment (radiotherapy, chemotherapy, targeted therapy,
immunotherapy or local-regional treatment). The adverse reactions related to anti-tumor
treatment (except hair loss) after the previous systemic anti-tumor treatment have not
recovered to NCI-CTC AE≤level 1; (5) Live vaccines have been vaccinated within 4 weeks
before administration of the study drug. Inactivated virus vaccines for seasonal
influenza and injection are allowed, but attenuated live influenza vaccines for
intranasal administration are not allowed; (6) The subject has any active, known or
suspected autoimmune disease. Subjects who are in a stable state and do not require
systemic immunosuppressant therapy are allowed to be enrolled; (7) Subjects who required
systemic treatment with corticosteroids (>10 mg/day of prednisone or equivalent doses of
other glucocorticoids) or other immunosuppressants within 14 days before the first dose
of study drug. Steroid replacement with inhaled or topical steroids and curative doses of
prednisone at doses > 10 mg/day is permitted in the absence of active autoimmune disease;
(8) Patients with a known history of interstitial pneumonia or highly suspected
interstitial pneumonia; or patients who may interfere with the detection or treatment of
suspected drug-related pulmonary toxicity; (9) Other active malignant tumors that require
simultaneous treatment; (10) Has a history of malignant tumors. Patients with basal cell
carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin,
or cervical carcinoma in situ who underwent potentially curative therapy and had no
disease recurrence within 5 years from the end of treatment were excluded; (11) Known
history of organ transplantation and allogeneic hematopoietic stem cell
transplantation;(12) Subjects who have undergone major surgery or severe trauma have less
than 14 days before enrollment; (13) Patients with active pulmonary tuberculosis should
be excluded. Patients suspected of having active pulmonary tuberculosis should be checked
for chest X-ray, sputum, and ruled out by clinical symptoms and signs. Patients with a
history of active tuberculosis infection within the previous 1 year, even if treated,
should be excluded; patients with a history of active tuberculosis infection more than 1
year ago should also be excluded. Unless it is proven that the duration and type of
antituberculosis treatment previously used was appropriate; (14) Severe acute or chronic
infection requiring systemic therapy； (15) Heart failure (New York Heart Association
Class III or IV) despite appropriate medical therapy. Patients with poorly controlled
coronary artery disease or poorly controlled arrhythmia, or a history of myocardial
infarction within 6 months prior to screening.
5. Neutrophil count <1.0×109/L, or hemoglobin <80g/L, or platelet count <90×109/L.
Hepatic insufficiency not related to tumor (transaminase more than 3 times the upper
limit of normal value and/or blood bilirubin greater than 2.0mg/dl). Renal
insufficiency not related to tumor (serum creatinine clearance <30 mL/min calculated
according to the CG formula).
6. Known history of positive human immunodeficiency virus (HIV) or known acquired
immunodeficiency syndrome (AIDS).
7. Untreated active hepatitis (hepatitis B: HBsAg positive and HBV DNA ≥ 500IU/mL;
hepatitis C: HCV RNA positive and abnormal liver function); co-infected with
hepatitis B and C.
8. Allergy to any study drug. 9. Pregnant and breastfeeding women.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Sun Yat-sen University cancer center
Address:
City:
Guangzhou
Zip:
510060
Country:
China
Status:
Recruiting
Contact:
Last name:
Yanxia Shi, PHD
Start date:
February 18, 2023
Completion date:
February 18, 2026
Lead sponsor:
Agency:
Sun Yat-sen University
Agency class:
Other
Source:
Sun Yat-sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05760053
