Safety of Cetuximab in Combination With Trifluridin Tipiracil in the Third-line Treatment of RASwt Metastatic Colorectal Cancer
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Enrollment
- 6
- Locations
- 1
- Primary Endpoint
- Incidence of DLT（Dose-limited toxicity）
Study Overview
Brief Summary
This was a single-arm, prospective study to investigate the safety of cetuximab in combination with trifluridin tipiracil (TAS-102) in the third-line treatment of Chinese patients with RAS wild-type mCRC.
Detailed Description
This was a single-arm, prospective study to investigate the safety of cetuximab in combination with trifluridin tipiracil (TAS-102) in the third-line treatment of Chinese patients with RAS wild-type mCRC. Cetuximab will be administered at a fixed dose of 500 mg/m2 once every 2 weeks; trifluridin tipiracil will be administered in a dose de-escalation design: dose level 1: 35 mg/m2 twice daily on days 1-5 once every 2 weeks; after 1 cycle will be observed, and if ≤ 2 patients experience DLT, this dose level will be the recommended phase II dose; if ≥ 3 patients experience DLT, additional 6 patients will receive dose level 0. ( Dose level 0: 30 mg/m2, twice daily, Days 1-5, once every 2 weeks;) If ≤ 2 individuals experience DLT, this dose level is the recommended Phase II dose; if ≥ 3 individuals experience DLT, the study will be stopped.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •18-75 years old male or female;
- •Histologically or cytologically confirmed metastatic colon or rectal adenocarcinoma; excluding appendiceal cancer and anal canal cancer;
- •Previously received second-line treatment, at least 2 standard chemotherapy regimens(including fluorouracil, capecitabine, irinotecan, oxaliplatin, raltitrexed and anti-VEGF, anti-EGFR, etc.), if already accepted anti-EGFR treatment achieved at least PR or above;
- •ECOG PS 0-1;
- •At least one measurable lesion by CT or MRI (according to RECIST 1.1 criteria, the longest diameter of tumor lesion CT/MRI scan ≥ 10 mm, lymph node lesion CT/MRI scan shortest diameter ≥ 15 mm);
- •RAS gene mutation detection results are wild-type. The test sample can be the primary tumor or metastasis sample;
- •Can receive oral drug treatment;
- •Normal function of major organs, meeting the following criteria within 14 days before the start of treatment:
- •neutrophil count ≥ 1.5 × 10*9/L;
- •Platelet count ≥ 75 × 10*9/L;
- •Hemoglobin ≥ 9.0 g/dL;
- •AST ≤ 2.5 × UNL (upper limit of normal) (if liver metastasis AST ≤ 5 × UNL);
- •ALT ≤ 2.5 × UNL (if liver metastasis AST ≤ 5 × UNL);
- •g.Creatinine clearance (calculated according to Cockcroft and Gault formula) > 60 mL/min or serum creatinine ≤ 1.5 × UNL;
- •Expected survival time > 3 months (90 days);
- •Women of childbearing potential must have used reliable contraception and had a negative pregnancy test within 7 days prior to enrollment and be willing to use an appropriate method of contraception during the trial and for 6 months after the last dose of trial drug. Males must agree to use an adequate method of contraception or have been surgically sterilized during the trial and for 6 months after the last dose of trial drug;
- •The patients voluntarily participated in this study and signed the informed consent form, with good compliance and cooperation in the follow-up.
Exclusion Criteria
- •Previously treated with regorafenib, fruquintinib, TAS-102;
- •Participated in another drug clinical trial in the past 4 weeks, or received systemic chemotherapy, radiotherapy or biological therapy in the past 4 weeks;
- •Known brain metastases or strongly suspected brain metastases;
- •Patients with known BARF mutations should be excluded;
- •Synchronous cancer or metachronous cancer with disease-free survival ≥ 5 years (except colorectal cancer), excluding mucosal cancer (esophageal cancer, gastric cancer, cervical cancer, non-melanoma skin cancer, bladder cancer, etc.) that has been cured or may be cured by local resection;
- •Factors that significantly affect the absorption of oral drugs, such as inability to swallow, chronic diarrhea and gastric intestinal obstruction; ucontrolled Crohn's disease or ulcerative colitis;
- •Serosal effusion (including pleural effusion, ascites, pericardial effusion) with clinical symptoms and requiring symptomatic treatment;
- •Pregnant or lactating women; patients of childbearing potential are unwilling or unable to take effective contraceptive measures;
- •Known to be allergic to the study drug, study drug class and its ingredients;
- •Conditions requiring systemic steroid treatment (except topical steroid and cetuximab pretreatment);
- •History of interstitial lung disease (interstitial pneumonia, pulmonary fibrosis, etc.) or CT findings of interstitial lung disease;
- •Active local or systemic infection requiring treatment;
- •Cardiac function classification (NYHA classification) ≥ Grade III or severe heart disease;
- •Known history of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) or active hepatitis B, C;
- •Toxicity not recovered (CTCAE > grade 1) or not completely recovered from previous anticancer surgery;
- •Patients judged by the Investigator as unsuitable for this study.
Arms & Interventions
Cetuximab and trifluridin tipiracil
Cetuximab will be administered at a fixed dose of 500 mg/m2 once every 2 weeks; trifluridin tipiracil will be administered in a dose de-escalation design: dose level 1: 35 mg/m2 twice daily on days 1-5 once every 2 weeks; Or dose level 0: 30 mg/m2, twice daily, Days 1-5, once every 2 weeks;
Intervention: Cetuximab + trifluridin tipiracil (Drug)
Outcomes
Primary Outcomes
Incidence of DLT（Dose-limited toxicity）
Time Frame: From Baseline to primary completion date, about 18 months
Determination of RP2D based on incidence of DLT
Secondary Outcomes
- Adverse Eevents(From Baseline to primary completion date, about 18 months)
Investigators
Hongli Liu
Director, Head of GI Department , Principal Investigator, Clinical Professor
Wuhan Union Hospital, China