Sintilimab, Cetuximab, Regorafenib,Combine,mCRC Clinical Trial
Official title:
Efficacy and Safety of Sintilimab Combined With Regorafenib and Cetuximab / Sintilimab Combined With Regorafenib in Posterior Line Therapy of Advanced Colorectal Cancer (Regosinti)
| NCT number | NCT04745130 |
| Other study ID # | Rui Liu |
| Secondary ID | |
| Status | Recruiting |
| Phase | Phase 2 |
| First received | |
| Last updated | |
| Start date | March 1, 2021 |
| Est. completion date | January 2024 |
The incidence of colorectal cancer ranks the third in the world and the mortality ranks the second in the world. The incidence and mortality of colorectal cancer have increased in China in the past decade. The incidence of colorectal cancer is associated with dietary patterns, obesity and lifestyle. The 2010 colorectal cancer survey in China showed that the incidence of colorectal cancer was low in the age group below 50 years old, and began to increase rapidly in the age group above 50 years old, reached the maximum in the age group above 70 years old, and decreased after 80 years old. For advanced colorectal cancer, systemic chemotherapy, local radiotherapy, synchronous or sequential chemoradiotherapy are lack of specificity, killing tumor cells as well as human normal cells, and the space for the traditional cytotoxic chemotherapy drugs to further improve the clinical efficacy of anti-malignant tumor is very limited. Therefore, molecular targeted tumor therapy with strong specificity and relatively small toxic and side effects has gradually become the fourth treatment mode following the three conventional treatment methods of surgery, radiotherapy and chemotherapy. Epidermal growth factor receptor (EGFR) is a clear target for treatment of advanced colorectal cancer. Immunotherapy has been a hot topic in recent years, In the field of colorectal cancer, studies on MSI-H population have been carried out successively since ASCO in 2015.However, the MSI-H population accounts for only 5% of patients with advanced colorectal cancer and 12-15% of total colorectal cancer, and the benefit population is very limited. Cetuximab is approved for the treatment of advanced colorectal cancer in the United States, Europe and China. Cetuximab in combination with chemotherapy is the standard treatment for RAS wild-type (RAS-WT) colorectal cancer. PD-1 monotherapy has been approved for patients with MSI-H/ DMMR colorectal cancer. The approved PD-1 mAb includes Nivolumab and Pembrolizumab. In some small trials, PD-1 monoclonal antibody combined with Regorafenib showed initial efficacy in patients with MSS type advanced colorectal cancer. EGFR signaling pathway blocker combined with PD-1 antibody, a new treatment mode, is of great significance to enrich the content of immunotherapy for patients with colorectal cancer, improve the survival prognosis of patients, and search for new efficacy predictors. In conclusion, this study, on the one hand, is expected to confirm that RAS and RAF wild-type advanced colorectal cancer and MSS type can benefit from Sintilimab combined with Regorafenib treatment, and at the same time, observe the effective rate of this regimen in the mutant group, so as to provide reference for clinical selection.
| Status | Recruiting |
| Enrollment | 90 |
| Est. completion date | January 2024 |
| Est. primary completion date | February 2023 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: - 1. Age =18 years old, no gender limitation; 2. Patients with unresectable recurrent or metastatic adenocarcinoma of the colon or rectum, proven histologically or cytologically; 3. Central laboratory tests confirm microsatellite stability (MSS) or microsatellite instability-low (MSI-L) or proficiency of MMR (PMMR); 4. For patients who have previously failed systemic therapy for relapsed or metastatic colorectal cancer, or who are intolerant to treatment, the time for disease progression after the last systemic therapy should not exceed 3 months?Systemic therapy must contain two or more of fluorouracil, oxaliplatin, and irinotecan, and may include or not targeted therapy (bevacizumab, cetuximab, etc.); 5. Patients must have a measurable disease (RECIST v1.1); 1. Non-lymph node lesions with the longest single diameter =10mm, or lymph node lesions with short diameter =15mm; 2. Lesion after previous local treatment, such as radiotherapy or ablation, can also be a measurable target if it has been clearly developed according to RECIST 1.1 and the longest single diameter is =10mm? 6.ECOG PS:0-1; 7.Life expectancy of more than 3 months; 8. Good organ function (no blood transfusion, no use of hematopoietic stimulating factor, no albumin or blood products within 14 days prior to examination); 1. platelets(PLT)=75,000 /mm3; 2. Absolute neutrophil(ANC)=1,500 /mm3; 3. hemoglobin(Hb)=9.0 g/dl; 4. international normalized ratio(INR)=1.5; 5. Total bilirubin =2 times the institutional upper limit of normal (ULN); 6. Aspartate aminotransferase(AST)(serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase(ALT)(serum glutamate pyruvate transaminase [SPGT])=3X institutional ULN (or=5 times ULN in case of liver metastasis); 7. Creatinine(Cr)=1.5×ULN and creatinine clearance(CrCl)=60mL/min; 9. Use contraception and avoid breast-feeding during the study period and for 3 months after the last dosing;Male subjects must agree to use contraception for the duration of the study and for 3 months after the last dosing; 10. Able to understand and willing to sign written informed consent? Exclusion Criteria: - 1. Study any other malignancy with a primary site or histological type different from that of CRC that was diagnosed within 5 years prior to treatment initiation, other than adequately treated basal or squamous cell skin cancer or cervical carcinoma in situ; 2. Central laboratory tests confirm microsatellite instability-high(MSI-H) or DNA mismatch repair defcient (dMMR); 3. Previous treatment with Regorafenib, PD-1/PD-L1/PD-L2 antibodies, or other co-stimulatory targets or checkpoints on T cells; 4. Known to be allergic to the study drug or excipient, or to similar drugs; 5. Known allergy to the study drug or excipient, or to similar drugs received immunosuppressive drugs within 2 weeks prior to the commencement of study treatment (excluding inhaled corticosteroids or other systemic steroids =10 mg/ day of prednisone or equivalent pharmacological dose); 6. A live attenuated vaccine was scheduled to be given 4 weeks before the start of study treatment or during the study period; 7. CYP3A4 inducers or inhibitors should not be discontinued 1 week before and during study treatment; 8. Central nervous system metastases are known to occur; 9. Any autoimmune disease or history of autoimmune disease; 10. Presenting any autoimmune disease or unwell controlled hypertension with a history of autoimmune disease (SBP =140 mmHg or Diastolic BP =90 mmHg); 11. Clear bleeding tendency, hemoptysis, hematemesis and stool? |
| Country | Name | City | State |
|---|---|---|---|
| China | Rui Liu | Tianjin | Tianjin |
| Lead Sponsor | Collaborator |
|---|---|
| Tianjin Medical University Cancer Institute and Hospital |
China,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Overall Survival (OS) | Overall Survival (OS) (median) was determined using the number of months measured from the initial date of treatment to the recorded date of death of participants. | Up to 2 years | |
| Secondary | Progression-free Survival (PFS) | Progression-free Survival (PFS) (median) was determined using the number of months measured from the initial date of treatment to the date of documented progression, or the date of death (in the absence of progression) of participants. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | up to 6 months | |
| Secondary | Objective Response Rate | The objective response rate is estimated by the proportion (percentage) of participants with the best response of complete response (CR), or partial response (PR) by RECIST 1.1 criteria, with corresponding exact 95% confidence limits being reported. | Up to 12months |