Clinical trial NCT01921673: Dovitinib Plus Docetaxel in Gastric Cancer
Official title: A Phase I-II Trial of Dovitinib Plus Docetaxel as Second-line Chemotherapy in Patients With Metastatic or Unresectable Gastric Cancer After Failure of First-line Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Gastric Cancer
Keywords: Gastric cancer
Phase I/II
Second-line chemotherapy
Dovitinib
Docetaxel
Refractory to first-line chemotherapy
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
First posted: 2013-08-13
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Docetaxel is currently one of standard second-line therapy in patients with gastric cancer. As angiogenesis and FGFR pathway has been suggested to be associated with gastric cancer, dovitinib, dual VEGFR and FGFR inhibitor, may have the potential to improve the outcomes of patients with gastric cancer. Therefore, we investigated the combination regimen of docetaxel and dovitinib.


Eligibility criteria: Inclusion Criteria:

1. Pathologically proven metastatic or unresectable adenocarcinoma of stomach or gastroesophageal junction
2. Patients with progressive disease (radiological confirmation required) after one line of chemotherapy except taxane for advanced gastric cancer in palliative setting
3. Presence of at least one evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
4. Age of 18 to 74 years
5. Estimated life expectancy of more than 3 months
6. Eastern Cooperative Oncology Group (ECOG) performance status 0\~2
7. Adequate bone marrow function (Absolute neutrophil counts ≥ 1,500/uL, hemoglobin ≥ 8.0g/dL, and platelet ≥ 100,000/uL)
8. Adequate renal function (creatinine \< 1.5mg/dL)
9. Adequate hepatic function (total bilirubin \< 1.5 mg/dL, transaminase \< 3 times the upper normal limit \[5 times for patients with liver metastasis\])
10. No prior anti-angiogenic therapy (anti-VEGF or VEGFR tyrosine kinase inhibitor etc) or FGF/FGFR inhibitor
11. No prior radiation therapy within 4 weeks of the study (Irradiated lesions should not be included in the evaluable lesions.)
12. Written informed consent

Exclusion Criteria:

1. Past or concurrent history of neoplasm other than gastric adenocarcinoma, except for curatively treated non-melanoma skin cancer or in situ carcinoma of the cervix uteri
2. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start
3. Bowel obstruction
4. Evidence of serious gastrointestinal bleeding
5. Presence of central nervous system (CNS) metastasis
6. History of significant neurologic or psychiatric disorders
7. Significant cardiac disease within 6 months of the study (congestive heart failure uncontrollable by medication, symptomatic coronary heart disease, or arrhythmia, myocardial infarction)
8. Left ventricular ejection fraction (LVEF) assessed by 2-D echocardiogram (ECHO) or multiple gated acquisition scan (MUGA), \< 45%
9. Uncontrolled hypertension defined by a SBP ≥ 160 mm Hg and/or DBP ≥ 100 mm Hg, with or without anti-hypertensive medication. Initiation or adjustment of antihypertensive medication (s) is allowed prior to study entry.
10. QTc \> 480 msec on screening ECG
11. Proteinuria defined by NCI CTCAE grade \> 1 at baseline as measured by a urine dipstick (2+ or greater) and confirmed by a 24 hour urine collection ( \> 1g/24hrs). Subjects may be re-screened if blood pressure is shown to be controlled with or without intervention
12. History of thrombotic or bleeding diathesis or coagulopathy
13. Serious non-healing wound, peptic ulcer, or bone fracture
14. Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months
15. Pregnant or lactating women, women of childbearing potential not employing adequate contraception
16. Other serious illness or medical conditions

Primary outcomes:
measure: Maximum tolerated dose
timeFrame: 6 months
measure: Progression-free survival
timeFrame: 2 year
Secondary outcomes:
measure: Response rate
timeFrame: 2 year
measure: Toxicity
timeFrame: 2 years
measure: Overall survival
timeFrame: 2 years
measure: Biomarker
timeFrame: Baseline and 2 weeks after study treatment
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
Study officials:
affiliation: Asan Medical Center
name: Yoon-Koo Kang, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lee JL, Ryu MH, Chang HM, Kim TW, Yook JH, Oh ST, Kim BS, Kim M, Chun YJ, Lee JS, Kang YK. A phase II study of docetaxel as salvage chemotherapy in advanced gastric cancer after failure of fluoropyrimidine and platinum combination chemotherapy. Cancer Chemother Pharmacol. 2008 Apr;61(4):631-7. doi: 10.1007/s00280-007-0516-6. Epub 2007 May 23.
citation: Wesche J, Haglund K, Haugsten EM. Fibroblast growth factors and their receptors in cancer. Biochem J. 2011 Jul 15;437(2):199-213. doi: 10.1042/BJ20101603.
citation: Yamamoto S, Yasui W, Kitadai Y, Yokozaki H, Haruma K, Kajiyama G, Tahara E. Expression of vascular endothelial growth factor in human gastric carcinomas. Pathol Int. 1998 Jul;48(7):499-506. doi: 10.1111/j.1440-1827.1998.tb03940.x.