Clinical trial NCT03244774: 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
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Gastric Adenocarcinoma
Lead sponsor: Fujian Cancer Hospital
Sponsor class: OTHER_GOV
First posted: 2017-08-10
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Dose limiting toxicity
timeFrame: From enrollment to completion of study. Estimated about 12 months.
measure: Maximum tolerance dose
timeFrame: From enrollment to completion of study. Estimated about 12 months.
Secondary outcomes:
measure: Objective response rate
timeFrame: From enrollment to 3 months after treatment
measure: Progression-free survival
timeFrame: From enrollment to progression of disease. Estimated about 6 months.
measure: Overall survival
timeFrame: From enrollment to death of patients. Estimated about 1 year.
Other outcomes:
Locations:
city: Fuzhou
country: China
facility: Rongbo Lin
state: Fujian
Study officials:
affiliation: Fujian Cancer Hospital
name: Rongbo Lin
role: PRINCIPAL_INVESTIGATOR
References: