Trial Title:
Toripalimab,Celecoxib and Regorafenib in the Treatment of Refractory Advanced Colorectal Cancer
NCT ID:
NCT05933980
Condition:
Colorectal Cancer
Liver Metastases
MSS
Conditions: Official terms:
Colorectal Neoplasms
Neoplasm Metastasis
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:
Rego+Tori+Cele
Description:
combination of Toripalimab,regorafenib and celecoxib
Arm group label:
regorafenib,Toripalima and celecoxib
Other name:
Bayer AG
Other name:
Innovent Biologics
Summary:
Research has found that patients with microsatellite instability (dMMR/MSI-H) type
colorectal cancer can achieve long-term survival through immune checkpoint inhibitors
(ICIs) treatment, but currently accounting for about 95% of MSS type mCRC, the benefits
from immune checkpoint inhibitors are very limited. REGONIVO is a Phase Ib study to
explore the efficacy and safety of regorafenib in combination with nivolumab in the
treatment of gastric cancer and colorectal cancer with MSS. The study enrolled 50
patients with advanced disease, including 25 cases of gastric cancer, 25 cases of
colorectal cancer, except for one case of colorectal cancer with MSI-H, and others were
MSS type. The results of the study showed that patients with colorectal cancer had an
objective response rate (ORR) of 36%.The ORR of liver matestasis vs. lung matestasis is
8.7% vs. 50%.
In this study, pMMR /MSS type patients with refractory advanced colorectal cancer without
liver metastasis were selected as the subjects. Regorafenib, Toripalimab and Celecoxib
were used to evaluate the maximum tolerable dose, objective response rate (ORR), total
survival time (OS), progression free survival time (PFS), disease control rate (DCR),
response duration (DoR) and safety of the subjects.
Detailed description:
At present, the microsatellite stabilized (MSS) type of advanced refractory metastatic
colorectal cancer (mCRC) has a poor median overall survival time of only about 7 months,
and there is a significant unmet clinical demand for the efficacy of posterior treatment.
Research has found that patients with microsatellite instability (dMMR/MSI-H) type
colorectal cancer can achieve long-term survival through immune checkpoint inhibitors
(ICIs) treatment, but currently accounting for about 95% of MSS type mCRC, the benefits
from immune checkpoint inhibitors are very limited. REGONIVO is a Phase Ib study to
explore the efficacy and safety of regorafenib in combination with nivolumab in the
treatment of gastric cancer and colorectal cancer with MSS. The study enrolled 50
patients with advanced disease, including 25 cases of gastric cancer, 25 cases of
colorectal cancer, except for one case of colorectal cancer with MSI-H, and others were
MSS type. The results of the study showed that patients with colorectal cancer had an
objective response rate (ORR) of 36%.The ORR of liver matestasis vs. lung matestasis is
8.7% vs. 50%.A phase Ib /Ⅱ clinical study REGOTORI enrolled 39 subjects, with a total ORR
of 15.2%, and the ORR of non-liver metastasis subjects compared with liver metastasis
subjects was 30% and 8.7% respectively. Based on the prospective small sample clinical
trial results of other regifenib combined with PD-1 monoclonal antibody drugs, the
overall ORR is between 0% and 33.3%, the ORR for non-liver metastases is between 20% and
50%, and the ORR for liver metastases is between 0% and 15%.
In this study, pMMR /MSS type patients with refractory advanced colorectal cancer without
liver metastasis were selected as the subjects. Regorafenib, Toripalimab and Celecoxib
were used to evaluate the maximum tolerable dose, objective response rate (ORR), total
survival time (OS), progression free survival time (PFS), disease control rate (DCR),
response duration (DoR) and safety of the subjects.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. With subject's consent and signed informed consent form, willing and capable of
following planned visits, research treatments, laboratory tests, and other trial
procedures
2. Subjects diagnosed with colon or rectal adenocarcinoma by pathology or cytology have
evidence of locally advanced lesions or metastases that cannot be surgically
removed, without liver metastasis, and all other histological types are excluded.
3. Age 18 and above.
4. The subject has received at least second-line standard chemotherapy in the past and
has failed. These standard treatment protocols must include fluorouracil,
Oxaliplatin, irinotecan, and Bevacizumab. Subjects with left colon cancer RAS/BRAF
V600E genotype of wild type must have received Cetuximab or Panitumumab and other
Epidermal growth factor receptor inhibitors. The definition of treatment failure is:
disease progression or intolerable toxic side effects occur during the treatment
process or within 3 months after the last treatment (One or more chemotherapy drugs
with a duration of ≥ 1 cycle for each frontline treatment until the disease
progresses; adjuvant/neoadjuvant treatment is allowed in the early stage. If there
is recurrence or metastasis during the adjuvant/neoadjuvant treatment or within 6
months after completion, adjuvant/neoadjuvant treatment is considered a failure of
frontline systemic chemotherapy for advanced diseases.
5. The Eastern Cancer Cooperative Group's Physical Fitness Score (ECOG) is 0-1 points.
6. Clearly identify measurable lesions that meet the requirements of the evaluation
criteria for solid tumor efficacy (RECIST version 1.1)
7. Based on the following laboratory test values obtained during the screening period,
appropriate organ function is achieved: white blood cell count ≥ 3.3 × 109/L,
neutrophil count ≥ 1.5 × 109/L, platelet count ≥ 75 × 109/L, serum total bilirubin ≤
1.5 × Upper limit of normal value (UNL), Aspartate transaminase or alanine
aminotransferase ≤ 2.5 × UNL (liver metastasis subjects should be ≤ 5 × ULN), serum
creatinine ≤ 1.5 × UNL.
8. Female subjects of childbearing age must carry out a serum Pregnancy test within 3
days before starting the study medication, and the result is negative, and are
willing to use a medically approved effective contraceptive measure (such as
Intrauterine device, contraceptives or condoms) during the study period and within 3
months after the last administration of the study medication.For male subjects whose
partners are women of childbearing age, they should undergo surgical sterilization
or agree to use effective methods of contraception during the study period and
within 3 months after the last study administration.
Exclusion Criteria:
1. Previous or concurrent existence of other active malignant tumors (except malignant
tumors that have received cured therapy and have not developed for more than 5 years
or Carcinoma in situ that can be cured through adequate treatment);
2. At present, there are duodenal ulcer, Ulcerative colitis, Bowel obstruction and
other digestive tract diseases or other conditions that may cause gastrointestinal
bleeding or perforation as determined by researchers.
3. Thrombosis or embolism events occurred within 6 months before the study, such as
cerebrovascular accident (including transient ischemic attack), Pulmonary embolism,
Deep vein thrombosis.
4. Within the 6 months prior to enrollment in the study, the following conditions
occurred: myocardial infarction, severe/unstable angina, NYHA grade 2 or above
cardiac insufficiency, clinically significant supraventricular or ventricular
arrhythmias, and symptomatic congestive heart failure.
5. Systemic use of antibiotics for ≥ 7 days within 4 weeks prior to enrollment in the
study, or unexplained fever >38.5°C occurring during the screening period/before the
first administration (according to the investigator's judgment, fever caused by
tumor can be enrolled).
6. Major operations such as laparotomy, thoracotomy, organ removal through Laparoscopy
or severe trauma were performed within 4 weeks before the study (Surgical incision
should be completely healed before randomization);
7. Within 7 days prior to enrollment in the study, there were uncontrollable pleural
effusion, ascites, or pericardial effusion after effective treatment.
8. Immunosuppressive drugs were used within 7 days before the enrollment study,
excluding nasal and inhaled Corticosteroid or systemic Sex hormone hormones with
physiological dose (i.e. no more than 10mg /d prednisone or other Corticosteroid
with physiological dose of equivalent drugs).
9. The general term standard for adverse events (NCICTCAE Version 5.0) caused by any
previous treatment that has not yet subsided has toxicity of grade 2 or above
(except anemia, hair loss, skin pigmentation and peripheral neurotoxicity related to
Oxaliplatin).
10. There are any active, known or suspected autoimmune diseases. Subjects who were in a
stable state at the time of enrollment and did not need systemic immunosuppression
treatment, such as type I diabetes, hypothyroidism only requiring hormone
replacement treatment, and skin diseases that did not need systemic treatment (such
as Vitiligo, psoriasis, and alopecia) are allowed.
11. There are Interstitial lung disease, non infectious pneumonia or uncontrollable
systemic diseases (such as diabetes, hypertension, Pulmonary fibrosis and acute
pneumonia).
12. HIV (HIV) infection or known acquired immunodeficiency syndrome (AIDS), untreated
active hepatitis (hepatitis B, defined as HBV-DNA ≥ 500 IU/ml; hepatitis C, defined
as HCV-RNA higher than the detection limit of the analytical method) or co infection
of hepatitis B and C.
13. Previously received antibodies against Programmed cell death protein-1 (PD-1) or its
ligand (PD-L1), antibodies against cytotoxic T-lymphocyte associated protein 4
(CTLA-4), or other drugs/antibodies that act on the costimulation or checkpoint
pathway of T cells.
14. Previous treatment with regofinib.
15. Medical history of known or suspected allergy to any relevant Drug allergy used in
the study.
16. Pregnant or lactating women.
17. Women of childbearing age who have not used or refused to use effective non hormonal
contraceptive methods (<2 years after their last menstrual period) or men who are at
risk of giving birth.
18. The presence of other serious physical or mental illnesses or laboratory examination
abnormalities may increase the risk of participating in the study, or interfere with
the results of the study, as well as subjects deemed unsuitable by the researcher
for participation in this study。
Gender:
All
Minimum age:
18 Years
Maximum age:
100 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Gastrointestinal Hospital, Sun Yat-sen University
Address:
City:
Guangzhou
Zip:
510655
Country:
China
Status:
Recruiting
Contact:
Last name:
Yanghong Deng, PhD
Phone:
008613925106525
Email:
dengyanh@mail.sysu.edu.cn
Investigator:
Last name:
Yanhong Deng, PhD
Email:
Principal Investigator
Start date:
December 19, 2023
Completion date:
December 20, 2025
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/NCT05933980
