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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

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:

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.

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

NCT ID

NCT03244774

First Posted

July 29, 2017

Last Updated

January 24, 2018

Sponsor

Fujian Cancer Hospital

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

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

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

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

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

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

rongbo_lin@163.com

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Phase I Study of the Combination of Apatinib and POF

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