Phase I Study of the Combination of Apatinib and POF

NCT03244774 | Unknown Phase 1 DMC

• 1 other identifier: FNF 007
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Gastric Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• 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

  From enrollment to completion of study. Estimated about 12 months.

• Maximum tolerance dose

  Maximum tolerance dose (MTD) is the dose of treatment in the cohort where there are 2 cases of DTL reported.

  From enrollment to completion of study. Estimated about 12 months.

Secondary Outcomes (3)

• Objective response rate

  From enrollment to 3 months after treatment

• Progression-free survival

  From enrollment to progression of disease. Estimated about 6 months.

• Overall survival

  From enrollment to death of patients. Estimated about 1 year.

Study Arms (1)

Apatinib plus POF

EXPERIMENTAL

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: 1. CTCAE Grade 4 event (except for neutropenia lasting for ≤ 5 days); 2. 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.

Drug: Apatinib; Drug: POF

Interventions

Apatinib DRUG

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:

Also known as: YN968D1

Apatinib plus POF

POF DRUG

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.

Also known as: Paclitaxel plus Oxaliplatin plus Luecovorin plus 5-Fluorouracil

Apatinib plus POF

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fujian Cancer Hospital: lead

Study Sites (1)

Rongbo Lin

Fuzhou, Fujian, 350014, China

RECRUITING

MeSH Terms

Interventions

apatinib; Paclitaxel; Oxaliplatin; Fluorouracil

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Rongbo Lin

  Fujian Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rongbo Lin

CONTACT

008613705919382; rongbo_lin@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2017
• First Posted: August 10, 2017
• Study Start: January 1, 2018
• Primary Completion: December 31, 2018
• Study Completion: June 30, 2019
• Last Updated: January 26, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)