Dovitinib Plus Docetaxel in Gastric Cancer

Asan Medical Center

Status and phase: Completed; Phase 2; Phase 1

Conditions: Gastric Cancer

Treatments: Drug: Dovitinib and docetaxel

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01921673

AMC1302

Details and patient eligibility

About

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.

Enrollment: 14 patients

Sex: All

Ages: 18 to 74 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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14 participants in 1 patient group

Dovitinib plus docetaxel

Experimental group

Description:

In phase I portion of the study Docetaxel 45-75 mg/m2, intravenous, every 3 weeks Dovitinib 200-500 mg, oral, 5 days on/2 days off In phase II portion of the study Recommended dose of docetaxel and dovitinib in phase I portion will be used.

Treatment:

Drug: Dovitinib and docetaxel