Clinical Trial Details
— Status: Recruiting
Administrative data
NCT number |
NCT05554276 |
Other study ID # |
CSH06R101 |
Secondary ID |
|
Status |
Recruiting |
Phase |
Phase 2
|
First received |
|
Last updated |
|
Start date |
August 1, 2023 |
Est. completion date |
December 31, 2025 |
Study information
Verified date |
July 2023 |
Source |
Shanghai Jiao Tong University Affiliated Sixth People's Hospital |
Contact |
Jie Fu, Dr |
Phone |
8602124058972 |
Email |
fujie74[@]sjtu.edu.cn |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
Based on various external factors and differences in the basic characteristics of patients,
in my country, it is not clear whether concurrent chemoradiotherapy can achieve optimal
therapeutic effect in patients with pathologically diagnosed stage IIB or above locally
advanced cervical cancer. Under the limitations of radiotherapy and surgery conditions in the
region, some patients will try neoadjuvant chemotherapy combined with PD-1 antibody therapy
before standard radiotherapy, hoping to reduce cancer focus and reduce infiltration. Thereby
reducing the scope of radiotherapy, better ensure the efficacy of late radiotherapy and
chemotherapy and reduce the side effects of radiotherapy. Judging from the review of such
patients, neoadjuvant chemotherapy combined with PD-1 antibody therapy + radical radiotherapy
seems to have certain efficacy and tolerance in the near future as expected. No statistical
analysis has been done on the long-term survival of patients. This topic intends to treat
inoperable locally advanced cervical cancer patients with neoadjuvant chemotherapy combined
with PD-1 antibody + radical radiotherapy, and explore the treatment-related toxic and side
effects and efficacy of neoadjuvant chemotherapy combined with PD-1 antibody + radical
radiotherapy. It is hoped that through this study, it will provide a reference for the
comprehensive treatment of inoperable locally advanced cervical cancer that has been
pathologically diagnosed in the future.
Description:
3.1 Overall study design and planning This study is a prospective, single-arm, phase II,
single-center study. Eligible patients with locally advanced cervical cancer entered the
trial arm, and all patients received three cycles of 21 days each, with chemotherapy on day 1
(nab-paclitaxel 150 mg/m2 plus cisplatin 75 mg/m2) and camrelizumab 200 mg, followed by
radical radiotherapy. Treatment-related acute events were recorded during treatment. Survival
period was followed up after the end of treatment, so far the trial treatment ended. (See the
following test flow diagram for details).
Schematic diagram of the test process:
3.2 Study population 3.2.1 Selection criteria
1. Age 18-70 years old;
2. Histologically diagnosed as cervical squamous cell carcinoma; clinical evaluation cannot
be surgically removed;
3. According to the 2018 International Federation of Obstetrics and Gynecology (FIGO)
cervical cancer staging for locally advanced patients, including inoperable stage IIB,
IIIA, IIIB, IIIC, IVa;
4. No previous treatment for cervical cancer;
5. According to RECIST version 1.1 criteria, there is at least one evaluable target lesion;
6. ECOG fitness status is 0-1 points;
7. The function of major organs is normal, that is, the following criteria are met:
1. The standard of blood routine examination must meet: (no blood transfusion within 14
days)
1. Hb≥90g/L:
2. ANC≥1.5x10^9/L;
3. PLT≥80x10^9/L;
2. The biochemical examination shall meet the following standards
1. BIL < 1.25 times the upper limit of normal (ULN);
2. ALT and AST < 2.5xULN;
3. Serum Cr≤ULN, endogenous creatinine clearance rate>50ml/min (Cockcroft-Gaut
formula); 8. Sign written informed consent before any trial-related activities; 9.
The researcher judges that the research protocol can be followed; 10. Patients who
are willing and able to comply with visiting arrangements, treatment plans,
laboratory tests and other research procedures.
3.2.2 Exclusion criteria
1. Previously received anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 or anti-CTLA-4
antibodies (including ipilimumab) or specifically targeted to T cell costimulation or immune
checkpoints Immunotherapy of any other antibody or drug of the pathway; 2. Major surgery ≤4
weeks before enrollment; 3. Those who have been confirmed to be allergic to PD-1 antibody or
its excipients; 4. Any active autoimmune disease or history of autoimmune disease (eg,
interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, myocarditis,
nephritis, hyperthyroidism, hypothyroidism (hormone replacement therapy is effective) can be
included later), etc.: patients with vitiligo or asthma who have been completely relieved in
childhood, do not require any intervention in adulthood, and require medical intervention
with bronchodilators can be included); 5. Previous or concomitant other malignancies (except
those that have been cured, cancer-free survival for more than 5 years, such as skin basal
cell carcinoma and papillary thyroid carcinoma, etc.); 6. Uncontrolled cardiac clinical
symptoms or diseases, such as: (1) NYHA II or higher heart failure (2) unstable striatal pain
(3) myocardial infarction within 1 year (4) clinically significant supraventricular or
ventricular Patients with arrhythmia requiring clinical intervention; 7. Subjects requiring
systemic treatment with corticosteroids (>10mg/day prednisone efficacy dose) or other
immunosuppressive agents within 14 days prior to administration of study drug, inhalation or
topical are allowed in the absence of active autoimmune disease Adrenal hormone replacement
with steroids and doses >10 mg/day of prednisone at therapeutic doses; 8. Active infection
requiring treatment; 9. Suffering from congenital or acquired immunodeficiency (such as HIV
infection), active hepatitis B (HBV-DNA≥104 (copy number/ml or 2000IU/ml) or hepatitis C
(positive for hepatitis C antibody, and HCV-RNA higher than the analytical method) detection
limit); 10. The patient has received other treatments prior to the patient's visit; 11.
Received live vaccine within 4 weeks prior to initiation of study treatment; 12. Known
history of psychotropic substance abuse, alcohol or drug abuse; 13. pregnant or breastfeeding
women; 14. According to the investigator's judgment, the subjects have other factors that may
cause them to be forced to terminate the study halfway, such as suffering from other serious
diseases (including mental diseases) that require concomitant treatment, severely abnormal
laboratory test values, and family or social factors. to the safety of subjects or the
collection of trial data; 15. Active pulmonary tuberculosis; 16. Serious infection (including
but not limited to hospitalization due to complications of infection, bacteremia or severe
pneumonia) occurred within 4 weeks before the start of study treatment; 17. Received systemic
immunostimulatory drug treatment (including but not limited to interferon or interleukin-2)
within 4 weeks before starting study treatment or within 5 drug half-lives (select the longer
of the two).
3.3 The number of cases and the method of grouping This study is a single-arm study, null
hypothesis: π≤δ. Alternative hypothesis: π>δ (π is the curative effect index rate of the
experimental group). The sample size was calculated based on the exact one-sided binomial
test. Assuming that α=0.05, 1-β=80%, and δ=50%, the curative effect of patients with advanced
cervical cancer in the past is about 30%, and the dropout rate is 5%. The required sample
size is calculated. Sample size calculations were performed using PASS 15.0.1. A total of 36
patients are planned to be enrolled.
3.4 Experimental drugs All patients received three cycles of chemotherapy and immunotherapy,
each of 21 days, of which day 1 received chemotherapy (nab-paclitaxel 150 mg/m2 plus
cisplatin 75 mg/m2) and camrelizumab 200 mg. All patients received routine antiemetic
prophylaxis in each cycle, including 12 mg dexamethasone (intravenous) on day 1 and 8 mg on
days 2-4. Definitive radiation therapy (including external beam and/or brachytherapy) was
administered 1 to 4 weeks after completion of three cycles of neoadjuvant therapy.
3.5 Study procedures and related examinations Screening period: blood, liver and kidney
function, cellular immune index, tumor index, HPV status, pelvic MRI, chest CT, abdominal
ultrasound, superficial lymph node ultrasound, PD-L1 comprehensive positive score and patient
quality of life self-assessment scale SF-36 score.
Selected treatment period: blood, liver and kidney function, and cellular immune indexes 1-3
days before and 1-7 days after each cycle of neoadjuvant chemotherapy and immunotherapy;
re-examination after 2 cycles of neoadjuvant therapy, before radiotherapy, and after
radiotherapy Local pelvic MRI examination; patient quality of life self-assessment scale
SF-36 score every 3 weeks; treatment-related acute events were recorded during treatment.
Follow-up: 1 month, 3 months, 6 months, 1 year, 2 years, 5 years after treatment, blood,
liver and kidney function, cellular immune index, tumor index, pelvic MRI, chest CT,
abdominal ultrasound, superficial lymph node ultrasound, etc. The treatment effect was
evaluated; at the same time, the intestinal condition of the patients was followed up to
evaluate the incidence of radiation enteritis and cystitis.
3.6 End Point indicators Primary endpoint: Objective Response Rate (ORR): refers to the
proportion of patients whose tumors shrink to a certain amount and maintain for a certain
period of time (more than 4 weeks), including CR+PR cases. CR (complete remission):
disappearance of all target lesions, PR (partial remission): reduction of the sum of the
length and diameter of the baseline lesions by ≥30%. ; Secondary endpoints: Safety (incidence
of treatment acute AEs, radiation enteritis, radiation cystitis); 2-year DFS and OS, and
5-year DFS and OS.
3.7 Criteria for discontinuation of clinical research
1. The patient himself or his legal representative requests to withdraw from the trial;
2. When a patient has an adverse reaction of grade 3 or above, and the adverse reaction
does not improve within a week after comprehensive symptomatic treatment, the study can
be terminated in advance by evaluating the efficacy, and the case will be treated as an
effectively completed case for statistical analysis;
3. The patient has disease progression (definition of disease progression event:
transformation to accelerated phase/blast blast phase or death from any cause).
3.8 Combination of medication and treatment
The concomitant medications and usage conditions that may be used as needed during the study
are as follows:
1. When adverse events caused by the trial drug require treatment, symptomatic treatment
drugs can be given;
2. When the treatment causes bone marrow suppression such as white blood cells and
platelets, relevant drugs can be given symptomatic treatment;
3. When the treatment causes abnormal liver and kidney function, related drugs can be given
symptomatic treatment;
4. When the treatment causes diarrhea and abdominal pain, related drugs can be given
symptomatic treatment;
5. When the treatment causes vomiting, antiemetics can be given;
6. When the patient has symptoms for other reasons, symptomatic treatment drugs can be
used.
All concomitant medications should be recorded and stated on the CRF form. 3.9 Follow-up and
medical interventions after the end of the study Blood, liver and kidney function, cellular
immune index, tumor index, pelvic MRI, chest CT, abdominal ultrasound, and superficial lymph
node ultrasound were measured at 1 month, 3 months, 6 months, 1 year, 2 years, and 5 years
after treatment. Further treatment should be given if recurrence or corresponding symptoms
occur.