A Clinical Study of Exploring Camrelizumab in the Treatment of Colorectal Mucinous Adenocarcinoma(MAC)

Phase 1

• Conditions: Colorectal Cancer
• Interventions: Drug: Carilizumab + anti-angiogenic TKIs (available with fuquitinib, rigofenib, apatinib, etc.)+Irinotecan; Drug: Carilizumab + anti-angiogenic TKIs (available with fuquitinib, rigofenib, apatinib, etc.)

• Registration Number: NCT04446091
• Lead Sponsor: Zhejiang Cancer Hospital

Brief Summary

This is an open-label, single center, non-randomized, phase Ⅱ trial to evaluate safety and efficacy of using the combination treatment of Camrelizumab with anti-angiogenic drugs and Chemotherapy of metastatic colorectal mucinous adenocarcinoma(MAC).

Detailed Description

Colorectal cancer contains multiple pathological types, and one of the more special pathological types is mucinous adenocarcinoma. The prognosis of patients with mucinous adenocarcinoma is not ideal.Some molecular and genetic factors may be related to the characteristics of mucinous adenocarcinoma, in which microsatellite instability and loss of mismatch repair proteins are a focus of current research. Microsatellite instability is often associated with poor differentiation and higher tumor stage. Adenocarcinoma that secretes a large amount of mucus in pathological features.so,In this study, the incidence of ORR and AEs was the main endpoint, and the efficacy and safety of Camrelizumab combined with anti-angiogenic drugs in the treatment of advanced colorectal mucinous adenocarcinoma were observed and evaluated.

Study Timeline

• Status Verified: 2020-06
• Study First Submitted: 2020-06-22
• Study First Submitted QC: 2020-06-22
• Last Update Submitted: 2020-06-22
• Study First Posted: 2020-06-24
• Last Update Posted: 2020-06-24
• Study Start: 2020-07-01
• Primary Completion: 2021-07-01
• Study Completion: 2022-07-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• 1. Join the study voluntarily and sign the informed consent;
• 2. Unresectable locally advanced or metastatic colorectal mucinous adenocarcinoma or colorectal adenocarcinoma containing mucinous gland components diagnosed by histopathology or cytology;
• 3. Patients who have received at least first-line and above systemic chemotherapy (which may include platinum, fluorouracil, or irinotecan-based) progress or intolerance (maintenance treatment progress after first-line chemotherapy can also be included). Simultaneous chemoradiotherapy for recurrence or metastasis after surgery is considered as first-line treatment; for radical concurrent chemoradiotherapy, neoadjuvant/adjuvant therapy (chemotherapy or radiochemotherapy), if disease progression occurs during treatment or within 6 months after stopping treatment, It should be counted as a failure of first-line treatment;
• 4. Age 18-75 years old (including boundary value, calculated on the day of signing informed consent), both men and women;
• 5. ECOG score 0-2 points;
• 6. Blood routine and liver and kidney function meet the following conditions: neutrophil count>1.5*10^9/L, hemoglobin concentration>90g/L, platelet count>80*109/L; ALT and AST<2.0*ULN (with liver The transferee may be <5.0*ULN);
• 7. Estimated survival time> 3 months;
• 8. Willing to accept long-term follow-up, willing to provide tumor tissue samples, willing to provide blood samples before and after treatment;

Exclusion Criteria

• 1. Known predisposition of inherited or acquired bleeding and thrombosis (such as hemophiliacs, coagulopathy, thrombocytopenia, etc.);
• 2. Urinary routines suggest that urine protein ≥ ++ and a confirmed 24-hour urine protein amount> 1.0 g;
• 3. Suffering from active infection, or unexplained fever within 7 days before medication ≥ 38.5℃, or baseline white blood cell count> 15×109/L;
• 4. There are contraindications for immunotherapy (including long-term use of hormones, radiation pneumonia has not been cured and cured within 3 months, etc.);
• 5. Active autoimmune diseases (such as vitiligo, psoriasis, hypothyroidism requiring hormone replacement therapy, etc.);
• 6. Patients with active hepatitis B or C, HIV patients, active tuberculosis, etc.;
• 7. Active infection requires antimicrobial treatment (for example, antibacterial drugs, antiviral drugs, antifungal drugs);
• 8. Known history of allogeneic organ transplantation and history of transplanted hematopoietic stem cells;
• 9. Patients with interstitial lung disease or previous history of interstitial pneumonia;
• 10. Those who have a history of psychotropic substance abuse and are unable to quit or have mental disorders;
• 11. Participated in clinical trials of other anti-tumor drugs within 2 weeks before enrollment;
• 12. Those who have used PD-1/PD-L1 and other immunotherapy drugs before entering the group;
• 13. Previous or concurrently suffering from other uncured malignant tumors, cured skin basal cell carcinoma, cervical carcinoma in situ, and superficial bladder cancer can be included;
• 14. Pregnant or lactating women; those with fertility who are unwilling or unable to take effective contraceptive measures;
• 15. According to the investigator's judgment, there are other factors that may affect the results of the study or lead to the forced termination of the study, such as alcoholism, drug abuse, other serious diseases (including mental illness) need to be treated together, and there are serious laboratory abnormalities , Accompanied by family or social factors, will affect the safety of the subject.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Three-drug group	Carilizumab + anti-angiogenic TKIs (available with fuquitinib, rigofenib, apatinib, etc.)+Irinotecan	Camrelizumab:200mg,iv,Q3W; Irinotecan:150mg/m2,iv 30\~90min,d1,Q3W Fruquintinib:5mg,po.qd,Day1\~21, repeat every 28 days;or Regorafenib: 80mg,po.qd,Day1\~21, repeat every 28 days;or Apatinib:250mg,po.qd,Day1\~21, repeat every 28 days;
Two-drug group	Carilizumab + anti-angiogenic TKIs (available with fuquitinib, rigofenib, apatinib, etc.)	Camrelizumab:200mg,iv,Q2W; Fruquintinib:5mg,po.qd,Day1\~21, repeat every 28 days;or Regorafenib: 80mg,po.qd,Day1\~21, repeat every 28 days;or Apatinib:250mg,po.qd,Day1\~21, repeat every 28 days;

Primary Outcome Measures

Name	Time	Method
ORR：Objective Response Rate	through study completion, an average of 2 year	Objective response rate evaluated by Independent Review Committee using radiographic examination according to RECIST1.1

Secondary Outcome Measures

Name	Time	Method
OS: overall survival	through study completion, an average of 2 year	time from randomization to death
PFS: progression-free survival	through study completion, an average of 2 year	time from randomization to progression and death
DCR: disease control rate	through study completion, an average of 2 year	partial rate of subjects evaluated as CR/PR/SD in all subjects

Trial Locations

Locations (1)

Zhejiang Province Cancer Hospital; 🇨🇳 Hangzhou, Zhejiang, China