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Phase I Study of the Combination of Apatinib and POF

Primary Purpose

Gastric Adenocarcinoma

Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Apatinib
POF
Sponsored by
Fujian Cancer Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastric Adenocarcinoma

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Patients with advanced unresectable, histologically confirmed adenocarcinoma of the gastric or gastroesophageal junction.
  2. No previous treatment with chemotherapy or radiation therapy.
  3. Ability to take medications orally.
  4. With or without measurable lesions.
  5. Patients must have a performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG) scale.
  6. Without serious system dysfunction and could tolerate chemotherapy. With normal marrow, liver and renal function: a hemoglobin (HGB) of ≥100g/L (without blood transfusion during 14 days); a leucopenia count of ≥4.0×109/L; a platelet count of ≥100×109/L; a total bilirubin (TBil) of ≤1.5 upper normal limitation (UNL); a creatinine (Cr) of ≤ 1.5 UNL; a creatinine clearance rate ≥ 50ml/min (Cockcroft-Gault); a alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) of ≤2.5 UNL or ≤5 UNL in case of liver metastasis.
  7. Life expectancy ≥3 months.
  8. With normal electrocardiogram results and no history of congestive heart failure.
  9. Without bleeding and thrombosis disease.
  10. With normal coagulation function: activated partial thromboplastin time (APTT), prothrombin time (PT) and INR, each ≤ 1.5 x ULN.
  11. Female subjects of child-bearing potential must agree to use contraceptive measures starting 1 week before the administration of the first dose of apatinib until 8 weeks after discontinuing study drug. Male subjects must agree to use contraceptive measures during the study and 8 weeks after last dose of study drug
  12. With written informed consent signed voluntarily by patients themselves or their supervisors witted by doctors.
  13. With good compliance and agree to accept follow-up of disease progression and adverse events.

Exclusion Criteria:

  1. Patients with a history of another neoplastic disease within the past three years, excluding basal cell carcinoma of the skin, cervical carcinoma in situ, or nonmetastatic prostate cancer.
  2. Patients with brain or central nervous system metastases, including leptomeningeal disease.
  3. Pregnant (positive pregnancy test) or breast feeding.
  4. Serious, non-healing wound, ulcer, or bone fracture.
  5. Significant cardiac disease as defined as: unstable angina, New York Heart Association (NYHA) grade II or greater, congestive heart failure, history of myocardial infarction within 6 months Evidence of bleeding diathesis or coagulopathy.
  6. History of a stroke or CVA within 6 months.
  7. Clinically significant peripheral vascular disease.
  8. Inability to comply with study and/or follow-up procedures.
  9. Patients with any other medical condition or reason, in that investigator's opinion, makes the patient unstable to participate in a clinical trial.

Sites / Locations

  • Rongbo LinRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Apatinib plus POF

Arm Description

This study will include a sequential evaluation of 3 subjects per cohort. Cohort 1: apatinib 250 mg per day and POF. Cohort 2: apatinib 375 mg per day and POF. Cohort 3: apatinib 500 mg per day and POF. Cohort 4: apatinib 625 mg per day and POF. Cohort 5: apatinib 750 mg per day and POF. A dose limiting toxicity (DLT) event is defined as any of the following events in the first 4-week period: CTCAE Grade 4 event (except for neutropenia lasting for ≤ 5 days); Grade 3 non-hematologic toxicity (except for nausea and vomiting that could be improved with optimal supportive care, escalation of alkaline phosphatase) If a DLT is experienced in any cohort, the cohort will be expanded to 6 subjects. If 2 DLTs are experienced in any cohort, the dose escalation ceased. The MTD was defined as the dose having at most two out of six patients experience DLT.

Outcomes

Primary Outcome Measures

Dose limiting toxicity
Dose limiting toxicity (DLT) is referred to grade 3 non-hematological toxicity or grade 4 hematological toxicity according to NCI CTCAE 4.03 criteria
Maximum tolerance dose
Maximum tolerance dose (MTD) is the dose of treatment in the cohort where there are 2 cases of DTL reported.

Secondary Outcome Measures

Objective response rate
Clinical response of treatment according to RESIST v1.1 criteria (ORR, objective response rate).
Progression-free survival
The length of time from enrollment until the time of progression of disease (PFS, progression-free survival).
Overall survival
The length of time from enrollment until the time of death (OS, overall survival).

Full Information

First Posted
July 29, 2017
Last Updated
January 24, 2018
Sponsor
Fujian Cancer Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03244774
Brief Title
Phase I Study of the Combination of Apatinib and POF
Official Title
Phase I Study of the Combination of Apatinib and POF (Paclitaxel Plus Oxaliplatin Plus 5-fluorouracil Plus Leucovorin)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2018
Overall Recruitment Status
Unknown status
Study Start Date
January 1, 2018 (Actual)
Primary Completion Date
December 31, 2018 (Anticipated)
Study Completion Date
June 30, 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fujian Cancer Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
In previous studies, we found that POF (A combination of oxaliplatin, fluorouracil and Paclitaxel) regimen appears to be of good efficacy and is well tolerated in patients with advanced gastric cancer. Apatinib is an orally antiangiogenic agent. It was approved and launched in China in 2014 as a 3rd-line treatment for patients with advanced gastric cancer. Therefore, investigators initialize this dose escalation phase I study to explore the safety of combination of apatinib and POF as first-line treatment for advanced gastric cancer. Investigators will analyze the maximum tolerated dose (MDT) and dose-limiting toxicity (DLT) of apatinib in this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastric Adenocarcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Apatinib plus POF
Arm Type
Experimental
Arm Description
This study will include a sequential evaluation of 3 subjects per cohort. Cohort 1: apatinib 250 mg per day and POF. Cohort 2: apatinib 375 mg per day and POF. Cohort 3: apatinib 500 mg per day and POF. Cohort 4: apatinib 625 mg per day and POF. Cohort 5: apatinib 750 mg per day and POF. A dose limiting toxicity (DLT) event is defined as any of the following events in the first 4-week period: CTCAE Grade 4 event (except for neutropenia lasting for ≤ 5 days); Grade 3 non-hematologic toxicity (except for nausea and vomiting that could be improved with optimal supportive care, escalation of alkaline phosphatase) If a DLT is experienced in any cohort, the cohort will be expanded to 6 subjects. If 2 DLTs are experienced in any cohort, the dose escalation ceased. The MTD was defined as the dose having at most two out of six patients experience DLT.
Intervention Type
Drug
Intervention Name(s)
Apatinib
Other Intervention Name(s)
YN968D1
Intervention Description
Apatinib 250mg p.o. qd in first cohort (3 subjects). 375mg p.o. qd in second cohort (3 subjects). 500mg p.o. qd in third cohort (3 subjects). 625mg p.o. qd in forth cohort (3 subjects); 750mg p.o. qd in fifth cohort (3 subjects). Other Name:
Intervention Type
Drug
Intervention Name(s)
POF
Other Intervention Name(s)
Paclitaxel plus Oxaliplatin plus Luecovorin plus 5-Fluorouracil
Intervention Description
The POF regimen consisted of a 3-hour infusion of paclitaxel (135 mg/m2) followed by oxaliplatin (85 mg/m2) and Calcium Levofolinate (200 mg/m2).Subsequently, a 46-hour infusion of fluorouracil (2400 mg/m2) was administered using an ambulatory pump, repeating the cycle every 14 days.
Primary Outcome Measure Information:
Title
Dose limiting toxicity
Description
Dose limiting toxicity (DLT) is referred to grade 3 non-hematological toxicity or grade 4 hematological toxicity according to NCI CTCAE 4.03 criteria
Time Frame
From enrollment to completion of study. Estimated about 12 months.
Title
Maximum tolerance dose
Description
Maximum tolerance dose (MTD) is the dose of treatment in the cohort where there are 2 cases of DTL reported.
Time Frame
From enrollment to completion of study. Estimated about 12 months.
Secondary Outcome Measure Information:
Title
Objective response rate
Description
Clinical response of treatment according to RESIST v1.1 criteria (ORR, objective response rate).
Time Frame
From enrollment to 3 months after treatment
Title
Progression-free survival
Description
The length of time from enrollment until the time of progression of disease (PFS, progression-free survival).
Time Frame
From enrollment to progression of disease. Estimated about 6 months.
Title
Overall survival
Description
The length of time from enrollment until the time of death (OS, overall survival).
Time Frame
From enrollment to death of patients. Estimated about 1 year.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with advanced unresectable, histologically confirmed adenocarcinoma of the gastric or gastroesophageal junction. No previous treatment with chemotherapy or radiation therapy. Ability to take medications orally. With or without measurable lesions. Patients must have a performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG) scale. Without serious system dysfunction and could tolerate chemotherapy. With normal marrow, liver and renal function: a hemoglobin (HGB) of ≥100g/L (without blood transfusion during 14 days); a leucopenia count of ≥4.0×109/L; a platelet count of ≥100×109/L; a total bilirubin (TBil) of ≤1.5 upper normal limitation (UNL); a creatinine (Cr) of ≤ 1.5 UNL; a creatinine clearance rate ≥ 50ml/min (Cockcroft-Gault); a alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) of ≤2.5 UNL or ≤5 UNL in case of liver metastasis. Life expectancy ≥3 months. With normal electrocardiogram results and no history of congestive heart failure. Without bleeding and thrombosis disease. With normal coagulation function: activated partial thromboplastin time (APTT), prothrombin time (PT) and INR, each ≤ 1.5 x ULN. Female subjects of child-bearing potential must agree to use contraceptive measures starting 1 week before the administration of the first dose of apatinib until 8 weeks after discontinuing study drug. Male subjects must agree to use contraceptive measures during the study and 8 weeks after last dose of study drug With written informed consent signed voluntarily by patients themselves or their supervisors witted by doctors. With good compliance and agree to accept follow-up of disease progression and adverse events. Exclusion Criteria: Patients with a history of another neoplastic disease within the past three years, excluding basal cell carcinoma of the skin, cervical carcinoma in situ, or nonmetastatic prostate cancer. Patients with brain or central nervous system metastases, including leptomeningeal disease. Pregnant (positive pregnancy test) or breast feeding. Serious, non-healing wound, ulcer, or bone fracture. Significant cardiac disease as defined as: unstable angina, New York Heart Association (NYHA) grade II or greater, congestive heart failure, history of myocardial infarction within 6 months Evidence of bleeding diathesis or coagulopathy. History of a stroke or CVA within 6 months. Clinically significant peripheral vascular disease. Inability to comply with study and/or follow-up procedures. Patients with any other medical condition or reason, in that investigator's opinion, makes the patient unstable to participate in a clinical trial.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Rongbo Lin
Phone
008613705919382
Email
rongbo_lin@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rongbo Lin
Organizational Affiliation
Fujian Cancer Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rongbo Lin
City
Fuzhou
State/Province
Fujian
ZIP/Postal Code
350014
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rongbo Lin, MD
Phone
86+13705919382
Email
rongbo_lin@163.com

12. IPD Sharing Statement

Plan to Share IPD
No

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Phase I Study of the Combination of Apatinib and POF

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