Pazopanib With 5-Fluorouracil, Leucovorin and Oxaliplatin (FLO) as 1st-line Treatment in Advanced Gastric Cancer; a Randomized Phase-II-study of the Arbeitsgemeinschaft Internistische Onkologie
- Subjects must provide written informed consent prior to performance of study-specific
procedures or assessments, and must be willing to comply with treatment and follow
- Age ≥ 18 years.
- Histologically confirmed adenocarcinoma of the stomach or the gastroesophageal
junction with either metastatic or locally advanced disease, incurable by operation.
- Eastern Cooperative Oncology Group (ECOG) performance status of < or = 2
- At least one unidimensional, measurable tumor parameter (according to RECIST 1.1)
- No preceding cytotoxic therapy (neoadjuvant or adjuvant treatment allowed if finished
> 6 months before inclusion)
- Adequate organ system function.
- Men and women must perform an adequate contraception.
- Female subjects who are lactating should discontinue nursing prior to the first dose
of study drug and should refrain from nursing throughout the treatment period and for
14 days following the last dose of study drug.
- Prior malignancy, except for curatively treated basal cell carcinoma of the skin and
in situ carcinoma of the cervix.
- Overexpression of HER-2, defined as IHC 3+ or IHC 2+ and FISH positive.
- Known hypersensitivity against 5-FU, leukovorin, oxaliplatin or other platinum
compounds or pazopanib.
- History or clinical evidence of central nervous system (CNS) metastases or
- Clinically significant gastrointestinal abnormalities that may increase the risk for
gastrointestinal bleeding or the absorption of investigational product
- Presence of uncontrolled infection.
- Corrected QT interval (QTc) > 480 ms using Bazett's formula.
- History of any one or more of the following cardiovascular conditions within the past
6 months: cardiac angioplasty or stenting, myocardial infarction, unstable angina,
coronary artery bypass graft surgery, symptomatic peripheral vascular disease, NYHA
III or IV congestive heart failure.
- Poorly controlled hypertension.
- History of cerebrovascular accident including transient ischemic attack (TIA),
pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6
- Prior major surgery or trauma within 28 days prior to first dose of study drug and/or
presence of any non-healing wound, fracture, or ulcer.
- Evidence of active bleeding or bleeding diathesis.
- Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels.
- Hemoptysis in excess of 2.5 ml within 8 weeks of first dose of study drug.
- Any serious and/or unstable pre-existing medical, psychiatric, or other condition
that could interfere with subject's safety, provision of informed consent, or
compliance to study procedures.
- Unable or unwilling to discontinue use of prohibited medications for at least 14 days
or five half-lives of a drug (whichever is longer) prior to the first dose of study
drug and for the duration of the study.
- Treatment with any of the following anti-cancer therapies: radiation therapy, surgery
or tumor embolization within 14 days prior to the first dose of pazopanib OR
chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal
therapy within 14 days or five half-lives of a drug (whichever is longer) prior to
the first dose of pazopanib. A neoadjuvant or adjuvant chemotherapy must be finished
at least 6 month before study entry.
- Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is
progressing in severity, except alopecia.
- Grade 3 or 4 diarrhea.
- Peripheral polyneuropathy > NCI Grade.
- Pregnant or lactating women.
- Men or women who are planning a pregnancy within the next six months.
- Participation in another clinical trial with investigational agents within the last
30 days prior to study start.
- The patient is a colleague or employed by the study investigator or by an involved
institution including the sponsor of the study.
- Patient is detained in a psychiatric unit or imprisoned.