Toripalimab,Celecoxib and Regorafenib in the Treatment of Refractory Advanced Colorectal Cancer (NCT05933980) | Clinical Trial Compass
UnknownPhase 2
Toripalimab,Celecoxib and Regorafenib in the Treatment of Refractory Advanced Colorectal Cancer
China44 participantsStarted 2023-12-19
Plain-language 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.
Who can participate
Age range18 Years – 100 Years
SexALL
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Inclusion criteria
✓. With subject's consent and signed informed consent form, willing and capable of following planned visits, research treatments, laboratory tests, and other trial procedures
✓. 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.
✓. Age 18 and above.
✓. 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.
✓. The Eastern Cancer Cooperative Group's Physical Fitness Score (ECOG) is 0-1 points.
. Clearly identify measurable lesions that meet the requirements of the evaluation criteria for solid tumor efficacy (RECIST version 1.1)
✓. 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.
✓. 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
✕. 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);
✕. 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.
✕. Thrombosis or embolism events occurred within 6 months before the study, such as cerebrovascular accident (including transient ischemic attack), Pulmonary embolism, Deep vein thrombosis.
✕. 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.
✕. 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).
✕. 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);
✕. Within 7 days prior to enrollment in the study, there were uncontrollable pleural effusion, ascites, or pericardial effusion after effective treatment.
✕. 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).