Safety and Efficacy Study of Chemotherapy Plus Apatinib as Second-line Therapy in Metastatic Colorectal Cancer

NCT03193814 | Withdrawn Phase 2

• 1 other identifier: XHZL
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of apatinib in combination with second-line FOLFOX or FOLFIRI for metastatic colorectal cancer in patients with disease progression during or after first-line therapy.

Conditions

Colorectal Cancer; Chemotherapy; Angiogenesis

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS) Time

  PFS was defined as the time from the date of randomization until the date of objectively determined progressive disease (PD) \[according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v). 1.1\] or death due to any cause, whichever was first. PD is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). Participants who died without a reported prior progression were considered to have progressed on the day of their death. Participants who did not progress or were lost to follow-up were censored at the day of their last radiographic tumor assessment.

  2 years

Secondary Outcomes (2)

• Percentage of Participants Achieving an Objective Response (Objective Response Rate)

  1 year

• Overall Survival (OS)

  2 years

Study Arms (1)

Chemotherapy + Apatinib

EXPERIMENTAL

chemotherapy regimens include: Folfox (Oxaplatin 85 mg/m2 IV over 2 hours, day 1; Leucovorin 400 mg/m2 over 2 hours, day 1; 5-FU 400 mg/m2 IV bolus on day 1, then 1200mg/m2/day x 2 days; repeat every 2 weeks) or Folfiri (Irinotecan 150-180 mg/m2 IV over 30-90 minutes, day 1; Leucovorin 400 mg/m2 over 2 hours, day 1; 5-FU 400 mg/m2 IV bolus on day 1, then 1200mg/m2/day x 2 days; repeat every 2 weeks)； apatinib 500mg po qd

Drug: Chemotherapy + Apatinib

Interventions

Chemotherapy + Apatinib DRUG

chemotherapy regimens could be folfox or folfiri; apatinib 500mg po qd

Also known as: chemotherpy plus apatinib mesylate

Chemotherapy + Apatinib

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically-confirmed inoperable colorectal adenocarcinoma excluding vermiform appendix cancer and anal canal cancer
• Age ≥18 years at the time of informed consent
• ECOG performance status (PS) of 0-1
• Written informed consent prior to study-specific screening procedures
• Life expectancy of at least 90 days
• Withdrawal from first-line chemotherapy (regardless of containing molecular-targeted drugs) for metastatic colorectal cancer due to intolerable toxicity or progressive disease, or relapse within 180 days after the last dose of adjuvant chemotherapy
• Adequate organ function according to following laboratory values obtained within 14 days before enrolment (excluding patients who received blood transfusions or hematopoietic growth factors within 14 days before the laboratory test) Neutrophil count: ≥1500/mm3 Platelet count: ≥10.0 x 104/mm3 Hemoglobin: ≥9.0 g/dL Total bilirubin: ≤1.5 mg/dL AST, ALT: ≤100 IU/L (≤200 IU/I if liver metastases present) Serum creatinine: ≤1.5 mg/dL
• Measurable or nonmeasurable disease based on the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
• Adequate coagulation function \[International Normalized Ratio (INR) ≤1.5 and Partial Thromboplastin Time (PTT) or activated PTT (aPTT) ≤1.5 x upper limit of normal (ULN)). Participants on full-dose anticoagulation must be on a stable dose of anticoagulant therapy and if on oral anticoagulation, must have an INR ≤3 and have no clinically significant active bleeding or pathological condition that carries a high risk of bleeding
• Consent to provide a historical colorectal cancer tissue sample for assessment of biomarkers and the tumor tissue sample is available
• Ability to provide signed informed consent

You may not qualify if:

• History of other malignancy with a disease-free interval \<5 years (other than curatively treated cutaneous basal cell carcinoma, curatively treated carcinoma in situ of the cervix, and gastroenterological cancer confirmed to be cured by endoscopic mucosal resection)
• With massive pleural effusion or ascites requiring intervention
• Radiological evidence of brain tumor or brain metastases
• Active infection including hepatitis
• Any of the following complication: i) Gastrointestinal bleeding or gastrointestinal obstruction (including paralytic ileus) ii) Symptomatic heart disease (including unstable angina, myocardial infarction, and heart failure) iii) Interstitial pneumonia or pulmonary fibrosis iv) Uncontrolled diabetes mellitus v) Uncontrolled diarrhea (that interferes with daily activities despite adequate therapy)
• Any of the following medical history: Myocardial infarction: History of one episode within one year before enrollment or two or more lifetime episodes i) Serious hypersensitivity to any of the study drugs ii) History of adverse reaction to fluoropyrimidines suggesting dihydropyrimidine dehydrogenase (DPD) deficiency
• Pregnant or lactating females, and males and females unwilling to use contraception
• Psychiatric disability that would preclude study compliance
• Otherwise determined by the investigator to be unsuitable for participation in the study
• Concurrent gastrointestinal perforation or history of gastrointestinal perforation with 1 year before enrollment
• History of pulmonary hemorrhage/hemoptysis ≥ Grade 2 (defined as bright red blood of at least 2.5mL) within 1 month prior to enrollment.
• History of laparotomy, thoracotomy, or intestinal resection within 28 days before enrollment
• Unhealed wound (except suture wounds from implantation of a central venous port), gastrointestinal ulcer, or traumatic fracture
• Current or recent (within 1 year) thromboembolism or cerebrovascular disease
• Currently receiving or requires anticoagulation therapy (\> 325 mg/day of aspirin)

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead

Related Publications (2)

• Tabernero J, Yoshino T, Cohn AL, Obermannova R, Bodoky G, Garcia-Carbonero R, Ciuleanu TE, Portnoy DC, Van Cutsem E, Grothey A, Prausova J, Garcia-Alfonso P, Yamazaki K, Clingan PR, Lonardi S, Kim TW, Simms L, Chang SC, Nasroulah F; RAISE Study Investigators. Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study. Lancet Oncol. 2015 May;16(5):499-508. doi: 10.1016/S1470-2045(15)70127-0. Epub 2015 Apr 12.

  PMID: 25877855 BACKGROUND

• Li J, Qin S, Xu J, Xiong J, Wu C, Bai Y, Liu W, Tong J, Liu Y, Xu R, Wang Z, Wang Q, Ouyang X, Yang Y, Ba Y, Liang J, Lin X, Luo D, Zheng R, Wang X, Sun G, Wang L, Zheng L, Guo H, Wu J, Xu N, Yang J, Zhang H, Cheng Y, Wang N, Chen L, Fan Z, Sun P, Yu H. Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Apatinib in Patients With Chemotherapy-Refractory Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction. J Clin Oncol. 2016 May 1;34(13):1448-54. doi: 10.1200/JCO.2015.63.5995. Epub 2016 Feb 16.

  PMID: 26884585 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Drug Therapy; apatinib

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)

Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Gastrointestinal Oncology Department

Study Record Dates

• First Submitted: June 17, 2017
• First Posted: June 21, 2017
• Study Start: December 1, 2019
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2024
• Last Updated: January 3, 2024

Record last verified: 2023-12