Trial Title:
Watch and Wait for NeoAdjuvant Concurrent Radiochemotherapy Combined With Camrelizumab in Patients With Resectable ESCC
NCT ID:
NCT05507411
Condition:
Esophageal Squamous Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Esophageal Squamous Cell Carcinoma
Immunomodulating Agents
Conditions: Keywords:
Esophageal Squamous Cell Carcinoma
NeoAdjuvant therapy
immunotherapy
Concurrent Radiochemotherapy
organ preservation
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Radiation
Intervention name:
Neoadjuvant Radiotherapy
Description:
41.4Gy/23F
Arm group label:
CCR-Surgery
Arm group label:
CCR-Watch and Wait
Arm group label:
Non-CCR
Intervention type:
Drug
Intervention name:
Neoadjuvant Chemotherapy
Description:
Paclitaxel for Injection （Albumin Bound): 50mg/m^2 QW Carboplatin: AUC=2 QW
Arm group label:
CCR-Surgery
Arm group label:
CCR-Watch and Wait
Arm group label:
Non-CCR
Intervention type:
Drug
Intervention name:
Immunotherapy
Description:
Camrelizumab 200mg Q3W
Arm group label:
CCR-Surgery
Arm group label:
CCR-Watch and Wait
Arm group label:
Non-CCR
Summary:
To observe the 1-year disease-free survival rate （1-year PFS） of patients with resectable
esophageal squamous cell carcinoma who received neoadjuvant chemoradiotherapy combined
with camrelizumab and achieved clinical complete remission with watchful waiting
strategy.
Detailed description:
This trial is a prospective, multicenter, randomized controlled phase II clinical study.
Eligible patients with thoracic esophageal squamous cell carcinoma in clinical stage
cT2-4aNanyM0, or cT1-3N+M0. The patient received radiotherapy (41.4Gy/23F), chemotherapy
(nab-paclitaxel combined with carboplatin), immunotherapy (Camrelizumab), and a
combination of imaging, endoscopy and biopsy pathology was performed 4-6 weeks after the
end of neoadjuvant therapy.
Evaluate (CRE1) to determine whether clinical complete resection (cCR) has been achieved.
If clinical complete resection is not reached, patients will receive radical surgery; For
subjects who have achieved clinical complete resection（cCR）, they will be randomly
divided into an operation group and an observational waiting group. After 14 weeks, the
combined imaging, endoscopy and biopsy pathological evaluation (CRE2) was performed again
to determine whether the clinical complete resection (CCR2) was reached. If the patient
has local progression and can be resected, radical surgery will be performed; if there is
distant progression, medical oncology treatment or supportive treatment will be
performed; if clinical complete resection remains, continuous and close imaging,
endoscopic and Biopsy pathology combined evaluation (CRE3-14). After achieving clinical
complete resection, patients who continue to be followed up for observation or undergo
radical surgery, if there is no contraindication to treatment, receive 14 cycles of
Camrelizumab maintenance therapy. During follow-up stage, if the patient develops local
progression and can be resected, radical surgery is performed; if distant progression
occurs, medical oncology treatment or supportive treatment is performed; if clinical
complete remission is still achieved, follow-up evaluation can be continued. Among them,
the 1-year disease-free survival rate under the esophagus-sparing treatment strategy
after achieving clinical complete remission was the main endpoint of the study.
To observe the disease-free survival（DFS）, overall survival（OS）, event-free
survival（EFS）, quality of life（QoL）, failure mode and choice of post-failure treatment
mode after neoadjuvant chemoradiotherapy combined with Camrelizumab therapy or after
surgical resection. And, the pathological complete remission rate and the main
pathological resection rate of the patients who underwent surgery.
The blood, stool and tissue samples of patients participating in the trial will be
retained for future detection of relevant markers and related laboratory research.
Treatment safety and toxicity, including acute and chronic toxicity, will be evaluated on
an ongoing basis during treatment and follow-up.
Any serious adverse drug reactions will be promptly reported to the hospital ethics
committee.
The relationship between relevant markers and clinical outcomes will be analyzed.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Sign the informed consent. Participants signed and dated written informed consent.
Informed consent must be signed prior to any protocol-related procedures that are
not part of the participant's routine medical care； Participants must be willing and
able to comply with scheduled visits, treatment regimens, and laboratory tests；
2. Participant type and target disease characteristics Eastern Collaboration Group
(ECOG) physical status score 0-1； Histologically confirmed esophageal cancer with
lesions located in the thoracic esophagus, AJCC/UICC esophageal cancer staging
(eighth edition) clinical stage cT2-4aNanyM0, or cT1-3N+M0； Presence of measurable
lesions according to RECIST criteria； Participants must have tumor tissue samples
available for PD-L1 IHC testing； No major associated pathological conditions that
increase the risk of surgery to unacceptable levels. Such as: esophageal perforation
and active esophageal bleeding, obvious trachea, thoracic large blood vessel
invasion； According to the surgeon's assessment, the total lung function can
withstand the proposed esophageal cancer resection；
3. Age and reproductive status Age ≥18 years old and ≤75 years old； Females of
childbearing potential (WOCBP) must have a negative serum or urine pregnancy test
(minimum sensitivity of 25 IU/L or equivalent for HCG) within 24 hours prior to
initiation of study treatment； Women must be non-nursing；
Exclusion Criteria:
1) Medical condition There is locally advanced unresectable (regardless of stage) or
metastatic disease.
Participants with Grade ≥2 Peripheral Neuropathy； Participants with active, known or
suspected autoimmune disease. Participants with type 1 diabetes, hypothyroidism requiring
only hormone replacement therapy, skin disorders that do not require systemic treatment
(eg, vitiligo, psoriasis, or alopecia), or disorders that are not expected to recur in
the absence of external stimuli are eligible to be enrolled； Participants requiring
systemic therapy with glucocorticoids (>10 mg prednisone equivalent daily) or other
immuno suppressive drugs within 14 days prior to treatment. In the absence of active
autoimmune disease, inhaled or topical steroids and adrenal hormone replacement therapy
at >10 mg prednisone-equivalent daily are permitted； Known history of positive human
immuno deficiency virus (HIV) test or known acquired immuno deficiency syndrome (AIDS)；
Participants with serious or uncontrolled medical illness； previous/concomitant therapy；
Received chest radiotherapy, chemotherapy, immunotherapy, or surgery of the esophagus,
esophagus and gastric junction, or stomach prior to the start of the trial.
Patients with severe cardiovascular or pulmonary disease, interstitial pneumonia, or
previous history of interstitial pneumonia； Patients with obvious esophageal ulcers,
moderate pain in the chest and back, and esophageal perforation symptoms； Physical
examination and laboratory test results
Laboratory screening values must meet the following criteria (using CTCAE 4th edition):
i) WBC < 2000/μL； ii) Neutrophils < 1500/μL； iii) Platelets < 100x103/μL； iv) Hemoglobin
< 9.0 g/dL； v) Serum creatinine <1.5 x ULN or calculated creatinine clearance (CrCl) < 50
mL/min (using Cockcroft-Gault formula)； vi) AST >3.0 x ULN； vii) ALT > 3.0 x ULN； viii)
Total bilirubin >1.5 x ULN (except for Gilbert syndrome participants, who had total
bilirubin < 3.0 x ULN)； Participants had active hepatitis B (positive for hepatitis B
surface antigen [HBsAg] or positive for hepatitis C virus (HCV) (positive for HCV RNA)；
i) Participants with previous or recovered HBV infection (defined as having hepatitis B
core antibody [HBcAb] and no HBsAg) are eligible. HBV DNA from these patients must be
obtained prior to treatment. Participants who are HBV carriers or require antiviral
therapy are not eligible； ii) Participants positive for HCV antibodies are eligible only
if PCR for HCV RNA is negative.； Active malignancy within the past 3 years, except for
locally curable cancers that have been significantly cured, such as basal or squamous
cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate,
cervix, or breast； Participants with serious or uncontrolled medical conditions； Allergic
Reactions and Adverse Drug Reactions； History of allergic reactions or hypersensitivity
reactions to study drug components Other exclusion criteria； Patients who do not
understand trial requirements, or who may not comply with trial requirements； Active
infection requiring systemic therapy 14 days prior to first dose Some obvious diseases
that the researchers believe should be excluded from this study；
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
The First Affiliated Hospital, Zhejiang University School of Medicine (FAHZU)
Address:
City:
Hanzhou
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Peng Ye
Phone:
+86-18969976868
Facility:
Name:
Zhejiang Cancer Hospital
Address:
City:
Hanzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Qixun Chen, PhD
Phone:
+86-13958108371
Email:
chenqixun64@163.com
Contact backup:
Last name:
Yongling Ji, PhD
Phone:
+86-13958085251
Facility:
Name:
Ningbo Medical Center Lihuili Hospital
Address:
City:
Ningbo
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Weiyu Shen
Phone:
+86-13805876129
Start date:
August 3, 2022
Completion date:
April 2027
Lead sponsor:
Agency:
Zhejiang Cancer Hospital
Agency class:
Other
Collaborator:
Agency:
Jiangsu HengRui Medicine Co., Ltd.
Agency class:
Industry
Source:
Zhejiang Cancer Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05507411
