Clinical trial NCT06485713: Efficacy and Safety of Trifluridine/Tipiracil Combined With Fufuquitinib for Third-line Treatment of mCRC
Official title: Efficacy and Safety of Trifluridine/Tipiracil Combined With Fufuquitinib Versus Trifluridine/Tipiracil and Fufuquitinib for Third-line Treatment of Unresectable Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Drug Therapy
Keywords: Metastatic Colorectal Cancer
Fufuquitinib
trifluridine/tipiracil
Combination therapy
Lead sponsor: First Affiliated Hospital of Wenzhou Medical University
Sponsor class: OTHER
First posted: 2024-07-03
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the efficacy and safety of trifluridine/tipiracil combined with fufuquitinib versus trifluridine/tipiracil and fufuquitinib in patients with unresectable metastatic colorectal cancer.


Eligibility criteria: Inclusion Criteria:

* 1.Age 18-75 (at the time of signing the informed consent);ECOG PS score: 0-1; Expected survival time \> 3 months.

  2.Patients with advanced colorectal adenocarcinoma confirmed by histopathology who had failed standard first - and second-line treatment.

  3.At least 1 measurable lesion was present according to RECIST1.1 criteria. 4.Good organ function, laboratory tests meet the following criteria:
  1. Hemoglobin ≥90g/L;Absolute count of neutrophils (ANC) ≥1.5×109/L;Platelet ≥100×109/L;
  2. ALT and AST≤2.5 upper limit of normal (ULN).ALP≤2.5 ULN;(if liver metastases ≤5 ULN);
  3. Total bilirubin (TBIL) \< 1.5 ULN;
  4. Serum creatinine (CR) \<1.5 ULN or creatinine clearance (CCR) ≥50ml/min;
  5. Serum albumin ≥30g/L;
  6. International Normalized ratio (INR), prothrombin time (PT), activated partial thrombin time (APTT) ≤1.5ULN;
  7. Thyrotropin (TSH) ≤ULN;If abnormal, T3 and T4 levels should be investigated, and normal levels can be included.

     5.cardiac color ultrasound: Left ventricular ejection fraction (LVEF) ≥50%. 6.Hypertension was well controlled. 7.Female participants of reproductive age should agree to use contraception during the study period and for 6 months after the study ends; Serum pregnancy test was negative within 7 days prior to study enrollment,and should be Non-lactation stage. Male subjects should agree to use contraception during the study period and for 6 months after the study ends.

     Exclusion Criteria:
* 1.Combined disease or history

  1. .Present or present with other malignancies within 3 years.
  2. .Have multiple factors affecting oral medication (such as inability to swallow, chronic diarrhea, or intestinal obstruction)
  3. .Gastrointestinal bleeding or perforation occurred during the first 4 weeks of enrollment
  4. .Patients with ulcerative colitis, Crohn's disease, and active inflammatory bowel disease during the first 4 weeks of enrollment
  5. .Uncontrolled pleural effusion, ascites, and moderate or greater pericardial effusion
  6. .Unmitigated toxic reactions above grade 1 of CTC AE due to any previous treatment, excluding alopecia.
  7. .Received major surgical treatment or significant traumatic injury within 28 days prior to enrollment
  8. .Patients with hematemesis, hematochezia, or any bleeding event ≥ CTCS AE level 3 within the previous 3 months, or with any signs of bleeding or history determined by the investigator to be ineligible for enrollment
  9. .Arteriovenous thrombosis occurred within 6 months, such as cerebrovascular accident, pulmonary embolism, etc
  10. .A history of psychotropic substance abuse and inability to abstain
  11. .Subjects with any severe and/or uncontrolled disease, including

      1. Uncontrolled hypertension
      2. Unstable angina pectoris / ≥ grade 2 cardiogenic chest pain;Myocardial infarction occurred within 12 months before randomization;≥ grade 2 heart failure;Restrictive heart disease;≥ grade 2 atrioventricular block, arrhythmia that cannot be stably controlled with drugs.
      3. Active infection
      4. Decompensated cirrhosis, active hepatitis;
      5. Renal failure requires hemodialysis or peritoneal dialysis
      6. A history of immunodeficiency, including HIV positive or other acquired, congenital immunodeficiency diseases, or a history of organ transplantation

      h.Diabetes with poorly controlled i.Urine routine showed urine protein ≥++, and 24h albuminuria quantitative \> 1.0 g g.History of neurological or psychiatric disorders 2.Subjects who, in the investigator's judgment, have a concomitant medical condition that seriously endangers subjects' safety or interferes with the completion of the study, or are deemed unsuitable for enrollment for other reasons.

Primary outcomes:
measure: Progression-free survival
timeFrame: up to 24 weeks
Secondary outcomes:
measure: Total survival time
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
Study officials:
References:
citation: Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.
citation: Quasar Collaborative Group; Gray R, Barnwell J, McConkey C, Hills RK, Williams NS, Kerr DJ. Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study. Lancet. 2007 Dec 15;370(9604):2020-9. doi: 10.1016/S0140-6736(07)61866-2.
citation: Twelves C, Wong A, Nowacki MP, Abt M, Burris H 3rd, Carrato A, Cassidy J, Cervantes A, Fagerberg J, Georgoulias V, Husseini F, Jodrell D, Koralewski P, Kroning H, Maroun J, Marschner N, McKendrick J, Pawlicki M, Rosso R, Schuller J, Seitz JF, Stabuc B, Tujakowski J, Van Hazel G, Zaluski J, Scheithauer W. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med. 2005 Jun 30;352(26):2696-704. doi: 10.1056/NEJMoa043116.
citation: Yothers G, O'Connell MJ, Allegra CJ, Kuebler JP, Colangelo LH, Petrelli NJ, Wolmark N. Oxaliplatin as adjuvant therapy for colon cancer: updated results of NSABP C-07 trial, including survival and subset analyses. J Clin Oncol. 2011 Oct 1;29(28):3768-74. doi: 10.1200/JCO.2011.36.4539. Epub 2011 Aug 22.