Nimotuzumab Combined With Trifluridine/Tipiracil in the Treatment of Refractory Metastatic Colorectal Cancer

NCT06343116 | Not Yet Recruiting Phase 3

• 1 other identifier: BPL-Nim-CRC-3001
• Study Type: interventional
• Target: 420
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a randomized, double-blind, placebo-controlled, multicenter study. The main purpose of the study is to evaluate the clinical efficacy and safety of nimotuzumab combined with trifluridine/tipiracil in third-line and beyond for the treatment of metastatic colorectal cancer (mCRC). This study planned to be divided into two parts: Part A and Part B. Part A (safety run-in) with a 3 + 3 study design, which primary endpoint is safety; Part B (main study) with a prospective, randomized, double-blind, placebo-controlled design, which primary endpoint is overall survival (OS).

Conditions

Refractory Metastatic Colorectal Cancer

Keywords

Nimotuzumab; trifluridine/tipiracil; metastatic colorectal cancer

Outcome Measures

Primary Outcomes (2)

• overall survival (OS)

  The primary endpoint is overall survival (OS, defined as from randomization to death due to any cause).

  Up to 18 months

• dose-limiting toxicity (DLT)

  DLTs at the end of the 4 weeks' treatment in part A (safety run-in).

  Up to 4 weeks for each participant in part A

Secondary Outcomes (8)

• Progression free survival (PFS)

  Up to 18 months

• time to progress (TTP)

  Up to 18 months

• overall response rate (ORR)

  Up to 18 months

• disease control rate (DCR)

  Up to 18 months

• duration of response (DoR)

  Up to 18 months

Other Outcomes (1)

• tumor-related markers

  Up to 18 months

Study Arms (2)

experimental group

EXPERIMENTAL

Nimotuzumab will be administered weekly (dose of nimotuzumab depends on part A). Trifluridine/tipiracil will be administered (35 mg/m2) twice daily, 5 days a week, with 2 days of rest, for 2 weeks, followed by a 14-day rest. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent or death due to any cause.

Drug: Nimotuzumab injection; Drug: Trifluridine/tipiracil

control group

PLACEBO COMPARATOR

Placebo will be administered weekly (dose of placebo depends on part A). Trifluridine/tipiracil will be administered (35 mg/m2) twice daily, 5 days a week, with 2 days of rest, for 2 weeks, followed by a 14-day rest. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent or death due to any cause.

Drug: Placebo; Drug: Trifluridine/tipiracil

Interventions

Nimotuzumab injection DRUG

Nimotuzumab will be administered weekly (dose of nimotuzumab depends on part A) until disease progression, unacceptable toxicity, withdrawal of consent or death due to any cause.

Also known as: Taixinsheng

experimental group

Placebo DRUG

Placebo will be administered weekly (dose of placebo depends on part A) until disease progression, unacceptable toxicity, withdrawal of consent or death due to any cause.

control group

Trifluridine/tipiracil DRUG

Trifluridine/tipiracil will be administered (35 mg/m2) twice daily, 5 days a week, with 2 days of rest, for 2 weeks, followed by a 14-day rest.

control group; experimental group

Eligibility Criteria

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

You may qualify if:

• Age 18-75 years old, gender unlimited;
• Histologically or cytologically confirmed diagnosis of colorectal cancer (CRC);
• Metastatic colorectal cancer, disease progression after previous second-line or above standard therapy;
• Efficacy of previous line therapy containing an anti-EGFR agent (panitumumab or cetuximab) with complete or partial response, or disease stable; and more than 4 months from last dose of anti-EGFR agent administered before randomization;
• MSS/pMMR status detected by IHC or PCR;
• RAS and BRAF wild-type status;
• ECOG Performance Status 0-1;
• Measurable disease according to RECIST criteria v1.1;
• Life expectancy of at least 3 months;
• Adequate organ and bone marrow function, defined as follows: hemoglobin≥9.0 g/dL; absolute neutrophil count (ANC)≥1.5×10\^9/L; white Blood Cell Count≥4×10\^9/L;platelets≥100×10\^9/L; serum total bilirubin (TBIL)≤1.5×ULN; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times the upper limit of normal (ULN), patients with liver metastases should be ≤ 5 times the ULN; serum creatinine≤1.5×ULN or estimated creatinine clearance \> 60 mL/min;
• Women of childbearing age should have a negative result of serum HCG or urine pregnancy tests within 72 hours prior to randomization (Postmenopausal women who have had amenorrhea for at least 12 months are considered sterile and women known to have had tubal ligation are not required to undergo pregnancy tests) ;
• Good compliance and signed informed consent.

You may not qualify if:

• Had other malignancies within the past 5 years or at the same time (exceptions include: cured thyroid cancer, non-melanoma skin cancer, carcinoma in situ of the cervix, stage I ductal carcinoma in situ, stage I endometrial cancer or other solid tumors, and effectively treated lymphoma with no evidence of disease for more than 5 years);
• Has a serious underlying medical condition that makes it impossible to safely administer the trial treatment. Including but not limited to active infections requiring systemic medication: compensatory heart failure (NYHA grade III and IV), unstable angina, and acute myocardial infarction within 3 months prior to enrollment;
• Patients who received trifluridine/tipiracil or treated with EGFR monoclonal antibody or EGFR tyrosine kinase inhibitor within four months;
• Known allergy to prescription or any component of the prescription used in this study;
• Women who are pregnant or are breastfeeding;
• Has brain metastases or any symptoms of brain metastases
• Factors that significantly affect oral drug absorption, such as dysphagia, chronic diarrhea, gastrointestinal obstruction, etc; Uncontrolled Crohn's disease or ulcerative colitis;
• Participated in other clinical trials within 4 weeks;
• With HIV, HPV, or syphilis infection, or active hepatitis (hepatitis B, hepatitis C)
• Other reasons that are not suitable to participate in this study according to the researcher's judgment.

Sponsors & Collaborators

• Biotech Pharmaceutical Co., Ltd.: lead

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

nimotuzumab; trifluridine tipiracil drug combination

Condition Hierarchy (Ancestors)

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

Study Officials

• Lin Shen

  Peking University Cancer Hospital & Institute

  STUDY CHAIR

Central Study Contacts

Lin Shen, Dr

CONTACT

13911219511; linshenpku@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2024
• First Posted: April 2, 2024
• Study Start: April 1, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: April 2, 2024

Record last verified: 2024-03