Neoadjuvant Fruquintinib Plus Tislelizumab Combined With mCapeOX Versus CapeOX for Mid-high pMMR/MSS Locally Advanced Rectal Cancer

NCT06443671 | Not Yet Recruiting Phase 2

• 1 other identifier: PKUCH-R09
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if neoadjuvant Fruquintinib and Tislelizumab combined with mCapeOX works to treat mid-high pMMR/MSS locally advanced rectal cancer patients compared with CapeOX. It will also learn about the safety of neoadjuvant Fruquintinib and Tislelizumab combined with mCapeOX. The main questions it aims to answer are:

• Does neoadjuvant Fruquintinib and Tislelizumab combined with mCapeOX improve the pCR rate of mid-high pMMR/MSS locally advanced rectal cancer patients?
• What medical problems do participants have when receiving neoadjuvant Fruquintinib and Tislelizumab combined with mCapeOX? Researchers will compare Fruquintinib and Tislelizumab combined with mCapeOX to CapeOX to see if neoadjuvant Fruquintinib and Tislelizumab combined with mCapeOX works to treat mid-high pMMR/MSS locally advanced rectal cancer patients. Participants will:
• Receive Fruquintinib and Tislelizumab combined with mCapeOX or CapeOX before surgery up to 4 cycles
• Receive radical operations and three years follow-up
• Keep a diary of their postoperative pathology results and survival

Conditions

Rectal Cancer

Keywords

local advanced rectal cancer; neoadjuvant chemotherapy; pMMR/MSS; Furoquinib and Tislelizumab; CapeOX

Outcome Measures

Primary Outcomes (1)

• Pathological complete response(pCR) rates

  Pathological complete response(pCR) rates are defined as no viable tumor cells remaining in the primary tumor and lymph nodes (ypT0N0), that is, subjects with level 0 of the AJCC 8th edition Tumor Regression Grading (TRG) scoring system proportion.

  10 days after surgery

Secondary Outcomes (4)

• Adverse events (AEs)

  From the beginning to the 21st day after the end of neoadjuvant treatment

• Major Pathologic Response(MPR)

  10 days after surgery

• 3-year event-free survival (EFS) rate

  36 months after randomization

• 3-year overall survival (OS) rate

  36 months after randomization

Study Arms (2)

CapeOX group

ACTIVE COMPARATOR

Receiving CapeOX treatment for up to four cycles before surgery: Capecitabine: 1000mg/m2, BID, PO, D1-14, Q3W; Oxaliplatin: 130 mg/m2, intravenous drip for 0-2 hours, D1, Q3W.

Drug: CapeOX

Fruquintinib and Tislelizumab combined with mCapeOX

EXPERIMENTAL

Receiving Fruquintinib plus Tislelizumab combined with mCapeOX treatment for up to four cycles before surgery: Fruquintinib: 3mg/d, QD, PO, Use for 2 weeks, stop for 1 week, Q3W; Tislelizumab: 200mg, D1, Intravenous infusion, Q3W; Capecitabine: 825mg/m2, BID, PO, D1-14, Q3W; Oxaliplatin: 100 mg/m2, intravenous drip for 0-2 hours, D1, Q3W.

Drug: Fruquintinib and Tislelizumab combined with mCapeOX

Interventions

CapeOX DRUG

Receiving CapeOX treatment for up to four cycles before surgery: Capecitabine: 1000mg/m2, BID, PO, D1-14, Q3W; Oxaliplatin: 130 mg/m2, intravenous drip for 0-2 hours, D1, Q3W.

CapeOX group

Fruquintinib and Tislelizumab combined with mCapeOX DRUG

Receiving Fruquintinib plus Tislelizumab combined with mCapeOX treatment for up to four cycles before surgery: Fruquintinib: 3mg/d, QD, PO, Use for 2 weeks, stop for 1 week, Q3W; Tislelizumab: 200mg, D1, Intravenous infusion, Q3W; Capecitabine: 825mg/m2, BID, PO, D1-14, Q3W; Oxaliplatin: 100 mg/m2, intravenous drip for 0-2 hours, D1, Q3W.

Fruquintinib and Tislelizumab combined with mCapeOX

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subjects voluntarily joined this study and signed an informed consent form;
• Age: 18-75 years old (including 18 and 75 years old), regardless of gender;
• Histologically confirmed rectal adenocarcinoma; Immunohistochemistry suggests pMMR, or PCR suggests MSS type patients;
• The tumor location meets the following criteria:
• Colonoscopy or digital examination shows that the distance from the lower edge of the tumor to the anus is 6-15cm or more than 4cm from the ARJ;
• MRI/CT determines that the lower edge of the tumor or the lower edge of the invading part is not higher than the sacral promontory pubic line;
• Preoperative staging meets the following conditions:
• Preoperative staging of tumor infiltration breaking through the intestinal muscle layer (T3) or above or accompanied by periintestinal lymph node metastasis;
• Non invasion of the intrinsic fascia of the rectum (MRF -);
• No swelling observed in lateral lymph nodes (short diameter not exceeding 7mm)
• There is no clear evidence of distant metastasis, and R0 resection is expected to be feasible after treatment; \*Baseline partial phase method: Rectal T2/DWI MR or Abdominal Pelvic CT or PET/CT or PET/MRI;
• Have not received any anti-tumor treatment for rectal cancer in the past, including surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc;
• ECOG score: 0-1 points;
• Able to swallow tablets and capsules normally;
• The plan is to complete the entire process of neoadjuvant therapy and undergo surgical resection;

You may not qualify if:

• Have a history of allergies to any anti-angiogenic targeted drugs, any components of monoclonal antibodies, capecitabine, oxaliplatin, or other platinum-based drugs in the past;
• Preoperative evidence suggests distant metastasis (including lymph node metastasis in the iliac foramen area) Metastasis of aortic lymph nodes and retroperitoneal lymph nodes above the root level of IMA; In addition to clear liver lung metastasis, liver lung nodules with unknown properties should also be excluded;
• Symptoms of incomplete or complete intestinal obstruction; Or preoperative colonoscopy may indicate narrowing of the intestinal lumen circumference; Or if the tumor is too large, colonoscopy cannot pass through the tumor;
• Those who are currently using immunosuppressive agents, systemic or absorbable local hormone therapy to achieve immunosuppressive effects (dosage\>10mg/day prednisone or other therapeutic hormones), and continue to use them within 2 weeks prior to enrollment;
• Receive attenuated live vaccines within 4 weeks prior to the first use of the study drug;
• Any active autoimmune disease or history of autoimmune disease (such as but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism; subjects with vitiligo or complete remission of childhood asthma in adulthood without any intervention can be included; subjects with asthma requiring medical intervention with bronchodilators cannot be included);
• Other malignant tumors in the past 5 years (excluding skin basal cell or squamous cell carcinoma, cervical carcinoma in situ, breast cancer, thyroid papillary carcinoma and small kidney carcinoma that are clinically cured after proper treatment (OS\>5 years));
• Congenital or acquired immune deficiency (such as HIV infected persons), or active hepatitis (hepatitis B: HBsAg positive and HBV DNA ≥ 104 copies/ml; hepatitis C: HCV antibody positive and HCV RNA\>1 × 103 copies/ml);
• Have uncontrolled clinical symptoms or diseases of the heart, such as: (1) NYHA grade 2 or above heart failure; (2) Unstable angina pectoris; (3) Have experienced myocardial infarction within one year; (4) Clinically significant supraventricular or ventricular arrhythmias require treatment or intervention;
• Suffering from hypertension and unable to achieve good control through antihypertensive drug treatment (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg);
• Active or uncontrolled severe infections (≥ CTCAE level 2 infection);
• Urinary routine indicates that urine protein is ≥ 2+, and the 24-hour urine protein content is\>1.0g;
• Known genetic or acquired bleeding and thrombotic tendencies (such as hemophilia, coagulation dysfunction, thrombocytopenia, splenic hyperfunction, etc.) or undergoing thrombolytic or anticoagulant therapy;
• The patient currently has digestive tract diseases such as active gastric and duodenal ulcers, ulcerative colitis, or active bleeding from unresectable tumors, or other conditions determined by the researcher that may cause gastrointestinal bleeding or perforation;
• Patients with significant evidence of bleeding tendency or medical history within the 3 months prior to enrollment (bleeding\>30 mL within 3 months, vomiting blood, black stool, and rectal bleeding), hemoptysis (fresh blood\>5 mL within 4 weeks), or thromboembolic events (including stroke events and/or transient ischemic attacks) within 12 months;

Sponsors & Collaborators

• Peking University Cancer Hospital & Institute: lead

Study Sites (1)

Peking University Cancer Hospital & Institute

Beijing, Haidian District, 100142, China

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

HMPL-013

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Central Study Contacts

Ai Wen Wu, M.D.

CONTACT

+8613911577190; wuaw@sina.com

Xiao Kang Lei, M.D.

CONTACT

+8618811181993; lxkpku@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2024
• First Posted: June 5, 2024
• Study Start: June 1, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2028
• Last Updated: June 5, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)