Trial Title:
The Combination of Hypofractionated Radiotherapy and Immunotherapy in Locally Recurrent Rectal Cancer
NCT ID:
NCT05628038
Condition:
Recurrent Rectal Cancer
Conditions: Official terms:
Rectal Neoplasms
Recurrence
Leucovorin
Folic Acid
Bevacizumab
Cetuximab
Capecitabine
Oxaliplatin
Irinotecan
Raltitrexed
Antibodies
Levoleucovorin
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:
Drug
Intervention name:
PD-1 antibody
Description:
PD-1 antibody (Toripalimab): 240mg q3w or 160mg q2w
Arm group label:
Treatment arm
Other name:
Toripalimab
Intervention type:
Drug
Intervention name:
Capecitabine
Description:
Capecitabine: 1000mg/m2 d1-14 q3w
Arm group label:
Treatment arm
Other name:
Xeloda
Intervention type:
Drug
Intervention name:
5FU
Description:
400 mg/m2 (bolus) and 2400 mg/m2 (continuous infusion for 48hr)
Arm group label:
Treatment arm
Intervention type:
Drug
Intervention name:
folinic acid
Description:
400 mg/m2 q2w
Arm group label:
Treatment arm
Intervention type:
Drug
Intervention name:
Oxaliplatin
Description:
130 mg/m² q3w or 85 mg/m² q2w
Arm group label:
Treatment arm
Intervention type:
Drug
Intervention name:
Irinotecan
Description:
180 mg/m² q2w and 200 mg/m² q3w
Arm group label:
Treatment arm
Intervention type:
Drug
Intervention name:
Raltitrexed
Description:
2 mg/m² q2w and 3 mg/m² q3w
Arm group label:
Treatment arm
Intervention type:
Drug
Intervention name:
Cetuximab
Description:
400 mg/m² q2w
Arm group label:
Treatment arm
Intervention type:
Drug
Intervention name:
Bevacizumab
Description:
5 mg/kg q2w or 7.5mg/kg q3w
Arm group label:
Treatment arm
Intervention type:
Radiation
Intervention name:
Radiation
Description:
25-40Gy/5Fx irradiation or 15-30Gy/5Fx reirradiation (pelvic radiation history) for
pelvic recurrence tumor.
35-60Gy/5-8Fx irradiation for distance metastasis tumor.
Arm group label:
Treatment arm
Summary:
The study is a prospective, single-center, single-arm, two-cohort, phase II clinical
trial. Patients aged 18 years or older who had pelvic recurrence rectal cancer with or
without resectable distant metastasis, with treatment naive disease (cohort A) or
progressive disease after first-line chemotherapy (cohort B), Eastern Cooperative
Oncology Group performance status of 0-1, will receive 25-40Gy/5Fx irradiation or
15-30Gy/5Fx reirradiation (pelvic radiation history), 18 weeks toripalimab and
investigator's choice of chemotherapy +/- target therapy, and stereotactic ablative
radiotherapy (SABR) for all metastatic lesions between chemoimmunotherapy cycles,
followed by multidisciplinary team (MDT) for decision:follow-up of complete response
(CR), radical surgery, sustained treatment of non resection, or exit.
The primary endpoint was local objective response rate. Secondary endpoints were
extrapelvic objective response rate, R0 resection rate, duration of response,
progression-free survival, overall survival, and safety and tolerability of the
treatment.
Shanghai Junshi Biomedical Technology Co., Ltd. Provides the first three cycles of
toripalimab for free and has purchased liability insurance for clinical trial subjects.
Detailed description:
For patients with locally recurrent rectal cancer (LRRC), response rate of
chemoradiotherapy is 40-50% and only approximately 40-50% of patients with recurrent
rectal cancer can undergo R0 resection. Recent studies have shown promising synergistic
effects of the combination of immunotherapy (PD-1/PD-L1 antibodies) and neoadjuvant
chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). Thus, for LRRC
patients, addition of immunotherapy to CRT is likely to further improve the response rate
and prognosis.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patient is 18-75 years old at the time of signing the informed consent form.
- ECOG performance status 0-1.
- MRI/enhanced CT confirmed pelvic recurrence. According to RECIST 1.1, there is at
least one measurable pelvic lesion.
- Distant metastasis lesions are no more than 5 and metastatic organ are no more than
3.
- No prior radiotherapy within 6 month.
- Previous system therapy. Patients Group Cohort A: participants with pelvic
recurrence who have not previously been treated with first-line chemotherapy. Cohort
B: Patients with disease progression or new lesions after first-line chemotherapy.
- Has an investigator determined life expectancy of at least 24 weeks.
- Demonstrate adequate organ function (bone marrow, liver, kidney and clotting
function) within 7 days before the first administration without using blood products
or hematopoietic stimulating factors.
- Non pregnant or lactating patients. Effective contraceptive methods should be used
during the study and within 6 months of the last administration.
- Fully informed and willing to provide written informed consent for the trial.
Exclusion Criteria:
- Neutrophil < 1.5×10^9/L, PLT < 100×10^9/L (PLT < 80×10^9/L in patients with liver
metastasis), or Hb < 90g/L; blood transfusion within 2 weeks before enrollment is
not allowed to meet the enrollment criteria.
- TBIL > 1.5 ULN, or TBIL > 2.5 ULN in patients with liver metastasis.
- AST or ALT > 2.5 ULN, or ALT and / or AST > 5 ULN in patients with liver metastasis.
- Cr > 1.5 ULN, or creatinine clearance < 50ml / min (calculated according to
Cockcroft Gault formula).
- APTT > 1.5 ULN, PT > 1.5 ULN (subject to the normal value of the clinical trial
research center).
- Serious electrolyte abnormalities.
- Urinary protein ≥ 2+, or 24-hour urine protein ≥1.0g/24h.
- Uncontrolled hypertension: SBP >140mmHg or DBP > 90mmHg.
- The presence of gastrointestinal diseases such as gastric or duodenal active ulcers,
ulcerative colitis or unresected tumours with active bleeding; or other conditions
likely to cause gastrointestinal bleeding or perforation; or unhealed
gastrointestinal perforation or gastrointestinal fistula after surgical treatment.
- A history of arterial thrombosis or deep vein thrombosis within 6 months; a history
of bleeding or evidence of bleeding tendency within 2 months.
- A history of heart disease within 6 months (including congestive heart failure,
acute myocardial infarction, severe/unstable angina, coronary artery bypass
grafting, cardiac insufficiency ≥ NYHA grade 2 and LVEF<50%).
- Uncontrolled malignant pleural effusion, ascites, or pericardial effusion.
- History of anti-PD-1, PD-L1, PD-L2, CTLA-4 or any other specific T cell
co-stimulation or checkpoint pathway targeted therapy.
- The presence of a clinically detectable second primary malignancy, or history of
other malignancies within 5 years excluding adequately treated non-melanoma skin
cancer, carcinoma in situ of cervix and superficial bladder tumour (non-invasive
tumour, or carcinoma in situ, or T1).
- A history of liver disease including, but not limited to HBV infection or HBV DNA
positive(≥1×10^4/ml), HCV infection or HCV DNA positive(≥1×10^3/ml) and liver
cirrhosis.
- Pregnant or lactating women or women who may be pregnant have a positive pregnancy
test before the first medication; Or the female participants themselves and their
partners who were unwilling to implement strict contraception during the study
period.
- The investigator considers that the subject is not suitable to participate in this
clinical study due to any clinical or laboratory abnormalities or compliance
problems.
- Serious mental abnormalities.
- The diameter of brain metastasis is greater than 3cm or the total volume is greater
than 30cc.
- Clinical or radiological evidence of spinal cord compression, or tumours within 3 mm
of the spinal cord on MRI.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Fudan University Shanghai Cancer Center
Address:
City:
Shanghai
Zip:
200032
Country:
China
Status:
Recruiting
Contact:
Last name:
Zhen Zhang, MD,PhD
Phone:
18801735029
Email:
zhen_zhang@fudan.edu.cn
Start date:
November 30, 2022
Completion date:
December 1, 2025
Lead sponsor:
Agency:
Fudan University
Agency class:
Other
Source:
Fudan University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05628038
