Trial Title:
Neoadjuvant Chemotherapy Combined With PD-1 + Radical Radiotherapy in Locally Advanced Cervical Cancer
NCT ID:
NCT05554276
Condition:
Neoadjuvant Chemotherapy
PD-1 Antibody
Radiotherapy
Cervical Cancer
Conditions: Official terms:
Uterine Cervical Neoplasms
Antibodies
Study type:
Interventional
Study phase:
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:
Combination Product
Intervention name:
neoadjuvant chemotherapy combined with PD-1 antibody + radical radiotherapy
Description:
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.
Arm group label:
neoadjuvant chemotherapy+ PD-1 antibody + radical radiotherapy
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.
Detailed 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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients who were pathologically diagnosed with cervical squamous cell carcinoma and
were assessed as unresectable.
Exclusion Criteria:
- Any active or present autoimmune disease (eg, interstitial pneumonia, uveitis,
enteritis, hepatitis, hypophysitis, vasculitis, myocarditis, nephritis,
hyperthyroidism, hypothyroidism)
Gender:
Female
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Vitalbeam
Address:
City:
Shanghai
Zip:
200233
Country:
China
Status:
Recruiting
Contact:
Last name:
Jie Fu, Dr
Phone:
8602124058972
Start date:
August 1, 2023
Completion date:
December 31, 2025
Lead sponsor:
Agency:
Shanghai Jiao Tong University Affiliated Sixth People's Hospital
Agency class:
Other
Source:
Shanghai Jiao Tong University Affiliated Sixth People's Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05554276
