Dovitinib Plus Docetaxel in Gastric Cancer

Gastric Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01921673
• Other study ID #: AMC1302
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: August 10, 2013
• Last updated: July 13, 2017
• Start date: August 2013
• Est. completion date: October 2016

Study information

• Verified date: July 2017
• Source: Asan Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: October 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

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

Related Conditions & MeSH terms

• Gastric Cancer
• Stomach Neoplasms

Intervention

Drug:
• Dovitinib and docetaxel
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.

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Asan Medical Center	Novartis Pharmaceuticals

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (3)

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. Epub 2007 May 23. — View 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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose	If dose limiting toxicities are experienced in two or more out of six patients in the cohort (more than 33% of patient cohort), that dose will be defined as the maximum tolerated dose.	6 months
Primary	Progression-free survival	Progression-free survival is defined as the time from the first treatment to the onset of progressive disease or to the date of death whichever comes first.	2 year
Secondary	Response rate	Proportion of patients with complete and partial response according to the Response Evaluation Criteria in Solid Tumors version 1.1	2 year
Secondary	Toxicity	Adverse events caused by study drugs according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0	2 years
Secondary	Overall survival	Time from start of study treatment to any cause of death	2 years
Secondary	Biomarker	FGFR2 copy number will be evaluated in blood and tumor tissue. Treatment efficacy including overall response rate, progression-free survival, and overall survival will be compared according to FGFR2 copy number determined by both FISH and real time PCR using TaqMan probe.	Baseline and 2 weeks after study treatment