Second-line Treatment of Metastatic Colorectal Cancer

NCT06242067 | Recruiting Phase 2

• 1 other identifier: KYLL-202210-057-1
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this multicenter, single-arm, observational cohort study is to investigate the efficacy and safety of irinotecan in combination with trifluridine-tipiracil and bevacizumab in colorectal cancer with prior oxaliplatin and fluoropyrimidine-based chemotherapy (including 5-FU/capecitabine/S-1) exposure in the metastatic setting or within 12 months of recurrence.

Conditions

Metastatic Colorectal Cancer

Keywords

colorectal cancer; bevacizumab; trifluridine-tipiracil/TAS-102; irinotecan

Outcome Measures

Primary Outcomes (1)

• progression-free survival(PFS)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first,

  from the date of randomization up to 36 months

Secondary Outcomes (5)

• objective response rate(ORR)

  from the date of randomization up to 36 months

• disease control rate(DCR)

  from the date of randomization up to 36 months

• overall survival(OS)

  from the date of randomization up to 36 months

• Adverse Events(safety)

  Up to 28 days after discontinuation of study drug or start of subsequent therapy.

• Duration of Response (DOR)

  from the date of randomization up to 36 months

Study Arms (1)

Irinotecan,Trifluridine-tipiracil in combination with Bevacizumab

EXPERIMENTAL

Drug: Trifluridine/tipiracil

Interventions

Trifluridine/tipiracil DRUG

patients received biweekly Trifluridine/tipiracil (30 mg/m2 twice daily; days 1-5), irinotecan (150 mg/m2; day 1) and bevacizumab (5 mg/kg; day 1).

Also known as: Irinotecan, Bevacizumab

Irinotecan,Trifluridine-tipiracil in combination with Bevacizumab

Eligibility Criteria

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

You may qualify if:

• All subjects are required to sign an informed consent form before starting the study-related procedure
• Age 18-75 years old, male or female.
• have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1, life expectancy \>3 months.
• Histologically or cytological proven metastatic or recurrent adenocarcinoma of the colon or rectum.
• Prior treatment with a fluoropyrimidine (5-fluorouracil \[5-FU\] or capecitabine) and oxaliplatin with bevacizumab or cetuximab targeted therapy as the first-line regimen.
• Recurrence or metastasis within 12 months after completion of adjuvant/neoadjuvant therapy with oxaliplatin and fluoropyrimidine-based drugs is also considered as the failure of first-line chemotherapy.
• At least one measurable metastatic lesion, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
• Adequate organ function: bone marrow, kidney, liver function (within 7 days before treatment start) Absolute neutrophil count ≥ 1.5×109/L Platelet count ≥ 100×109/L Hemoglobin≥ 90g/L (no history of blood transfusion within 7 days); Creatinine clearance≥ 60 ml/min (Cockcroft-Gault formula) Bilirubin ≤ 1.5 x the upper limit of normal (ULN) Glutamate aminotransferase (AST)/ alanine aminotransferase (ALT) levels ≤2.5 x ULN or =\< 5 x ULN if with hepatic metastases; Alkaline phosphatase (AKP) ≤ 2.5 x ULN or =\< 5 x ULN if with hepatic metastases;
• Urine protein \<1+ or 24-hour urine protein \<1 gram;
• International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN or within the range if receiving anticoagulant therapy;
• Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence; IUDs, etc) during the study period and within 90 days of the last study medication. All female patients will be considered fertile unless they have spontaneous menopause, artificial menopause, or sterilization (e.g., hysterectomy, bilateral adnexectomy, or radiation ovarian irradiation).

You may not qualify if:

• First-line treatment with irinotecan;
• Patients with KRAS/NRAS/BRAF wild-type and not treated with cetuximab in the first line.
• Patients with dMMR/MSI-H (deficient mismatch repair/microsatellite instability-high) status;
• Symptomatic brain or meningeal metastases (except for brain metastases that have undergone local radiotherapy or surgery for more than 6 months and stable disease control)
• Previous or current severe bleeding (bleeding \>30ml within 3 months), coughing up blood (\>5ml of fresh blood within 4 weeks) or cerebrovascular accident (excluding lacunar cerebral infarction, minor cerebral ischemia or transient ischemic attack, etc.) within half a year before the first use of the study drug, myocardial infarction, unstable angina, poorly controlled arrhythmias (including QTc interval ≥450 ms for men and 470 ms for women≥) (QTc interval is calculated by Fridericia formula). According to the New York College of Cardiology (NYHA) standard class III or IV cardiac insufficiency or cardiac ultrasound: left ventricular ejection fraction (LVEF) \< 50%.
• Uncontrolled hypertension: systolic blood pressure \>140mmHg, diastolic blood pressure \> \>90mmHg;
• Digestive tract diseases or states that the investigator determines may affect drug absorption, including but not limited to active gastric and duodenal ulcers, ulcerative colitis and other digestive tract diseases or active bleeding in unresected gastrointestinal tumors, or other conditions that the investigator determines may cause gastrointestinal bleeding or perforation or obstruction;
• History of second primary malignancy within 5 years prior to enrollment, excluding basal cell skin carcinoma or in-situ cervical carcinoma after radical resection;
• Have known active infection, including but not limited to human immunodeficiency virus (HIV) infection, a history of liver disease known to be significant, including but not limited to hepatitis B virus (HBV) infection and HBV DNA positive (≥1×104/ml); hepatitis C virus infection (HCV) with positive HCV RNA (≥1×103/ml), or cirrhosis, etc.
• Unresolved toxicities from prior therapy of \> grade 1, excluding alopecia; Any other disorders, metabolic abnormality, physical examination abnormality, or laboratory abnormality which has reason to suspect that the patient not suitable for the study or will affect the interpretation of the results. Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug.

Sponsors & Collaborators

• Qilu Hospital of Shandong University: lead
• The Affiliated Hospital of Qingdao University: collaborator
• Shandong Provincial Hospital: collaborator
• Qianfoshan Hospital: collaborator
• Binzhou People's Hospital: collaborator
• Binzhou Medical University: collaborator
• Yantai Yuhuangding Hospital: collaborator
• Linyi Tumour Hospital: collaborator

Study Sites (1)

Qilu hospital of Shandong University

Jinan, Shandong, 250012, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

trifluridine tipiracil drug combination; Irinotecan; Bevacizumab

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

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jing Hao, Dr.

  Qilu hospital of Shandong University, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

xiangling Wang, Dr.

CONTACT

8653182169841; xlwang71@163.com

Study Design

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

Study Record Dates

• First Submitted: January 28, 2024
• First Posted: February 5, 2024
• Study Start: April 23, 2023
• Primary Completion: December 1, 2024
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 5, 2024

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)