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

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ClinicalTrials.gov Identifier: NCT03193814
Recruitment Status : Not yet recruiting
First Posted : June 21, 2017
Last Update Posted : September 6, 2018
Sponsor:
Information provided by (Responsible Party):
Tao Zhang, Wuhan Union Hospital, China

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.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Chemotherapy Angiogenesis Drug: Chemotherapy + Apatinib Phase 2

Detailed Description:
Angiogenesis is an important therapeutic target in metastatic colorectal carcinoma. Apatinib is a potent oral inhibitor of the intracellular domain and emerging as original antiangiogenic opportunities. We assessed 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Study Evaluating the Safety and Efficacy of FOLFOX Plus Apatinib or FOLFIRI Plus Apatinib as Second-line Therapy in Metastatic Colorectal Cancer
Estimated Study Start Date : December 1, 2019
Estimated Primary Completion Date : December 1, 2020
Estimated Study Completion Date : December 1, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Chemotherapy + Apatinib
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
chemotherapy regimens could be folfox or folfiri; apatinib 500mg po qd
Other Name: chemotherpy plus apatinib mesylate




Primary Outcome Measures :
  1. Progression-free Survival (PFS) Time [ Time Frame: 2 years ]
    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.


Secondary Outcome Measures :
  1. Percentage of Participants Achieving an Objective Response (Objective Response Rate) [ Time Frame: 1 year ]
    The objective response rate is equal to the proportion of participants achieving a best overall response of partial response or complete response (PR + CR). Response was defined using RECIST, v. 1.1 criteria. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm and normalization of tumor marker level of non-target lesions; PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions taking as reference the baseline sum diameter.

  2. Overall Survival (OS) [ Time Frame: 2 years ]
    OS was defined as the time in months from the date of randomization to the date of death from any cause. For participants not known to have died as of the cut-off date, OS was censored at the last known date alive.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically-confirmed inoperable colorectal adenocarcinoma excluding vermiform appendix cancer and anal canal cancer
  2. Age ≥18 years at the time of informed consent
  3. ECOG performance status (PS) of 0-1
  4. Written informed consent prior to study-specific screening procedures
  5. Life expectancy of at least 90 days
  6. 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
  7. 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
  8. Measurable or nonmeasurable disease based on the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
  9. 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
  10. Consent to provide a historical colorectal cancer tissue sample for assessment of biomarkers and the tumor tissue sample is available
  11. Ability to provide signed informed consent

Exclusion Criteria:

  1. 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)
  2. With massive pleural effusion or ascites requiring intervention
  3. Radiological evidence of brain tumor or brain metastases
  4. Active infection including hepatitis
  5. 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)
  6. 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
  7. Pregnant or lactating females, and males and females unwilling to use contraception
  8. Psychiatric disability that would preclude study compliance
  9. Otherwise determined by the investigator to be unsuitable for participation in the study
  10. Concurrent gastrointestinal perforation or history of gastrointestinal perforation with 1 year before enrollment
  11. History of pulmonary hemorrhage/hemoptysis ≥ Grade 2 (defined as bright red blood of at least 2.5mL) within 1 month prior to enrollment.
  12. History of laparotomy, thoracotomy, or intestinal resection within 28 days before enrollment
  13. Unhealed wound (except suture wounds from implantation of a central venous port), gastrointestinal ulcer, or traumatic fracture
  14. Current or recent (within 1 year) thromboembolism or cerebrovascular disease
  15. Currently receiving or requires anticoagulation therapy (> 325 mg/day of aspirin)
  16. Bleeding diathesis, coagulopathy, or coagulation factor abnormality (INR ≥1.5 within 14 days before enrollment)
  17. Uncontrolled hypertension
  18. Urine dipstick for proteinuria >+2

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03193814


Contacts
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Contact: Tao Zhang, MD 862785871982 1277577866@qq.com
Contact: Zhenyu Lin, MD 862785871982 tojilin@gmail.com

Sponsors and Collaborators
Wuhan Union Hospital, China

Publications:
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Responsible Party: Tao Zhang, Chief of Gastrointestinal Oncology Department, Wuhan Union Hospital, China
ClinicalTrials.gov Identifier: NCT03193814     History of Changes
Other Study ID Numbers: XHZL
First Posted: June 21, 2017    Key Record Dates
Last Update Posted: September 6, 2018
Last Verified: September 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Apatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action