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A Randomized Phase II Study of Capecitabine and Cisplatin (XP) +/- Sorafenib (Nexavar®) in Patients With Advanced Gastric Cancer

Phase 2
18 Years
75 Years
Open (Enrolling)
Malignant Neoplasm of Stomach, Effects of Chemotherapy

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Trial Information

A Randomized Phase II Study of Capecitabine and Cisplatin (XP) +/- Sorafenib (Nexavar®) in Patients With Advanced Gastric Cancer

Inclusion Criteria:

1. Age 18-75

2. Histological or cytological documentation of gastric adenocarcinoma or
gastroesophageal junction adenocarcinoma.;

3. Metastatic gastric adenocarcinoma or metastatic gastroesophageal junction
adenocarcinoma, initially diagnosed or recurrent.

4. Measurable disease according to Response Evaluation Criteria in Solid Tumors

5. ECOG Performance Status of 0 or 1

6. Life expectancy of at least 3 months

7. Adequate bone marrow, liver and renal function as assessed by the following
laboratory requirements:

- Hemoglobin ≥ 9.0 g / dl

- Absolute neutrophil count (ANC) ≥1,500 / mm3

- Platelet count ≥ 100,000 / mm3

- Total bilirubin < 1.5 x upper limit of normal

- ALT and AST < 2.5 x upper limit of normal (< 5 x ULN for patients with liver
involvement of their cancer)

- International normalized ratio of PT (PT-INR) / PTT < 1.5 x ULN

8. Creatinine Clearance ≥ 60 ml / min (based on Cockcroft and Gault formula)

9. Ability to understand and willingness to sign a written informed consent. Signed
informed consent must be obtained prior to any study specific procedures

Exclusion Criteria:

1. Patients with local-regional gastric or gastroesophageal adenocarcinoma (no
para-aortic nodes or visceral structure-invading primary [T4]) who can potentially
become candidates for surgery with curative intent following systemic therapy

2. History of cardiac disease:

- Congestive heart failure >NYHA class 2; unstable angina (angina symptoms present
at rest), new-onset angina (began within last three months prior to
randomization) or myocardial infarction within six months prior to

- Ventricular arrhythmias requiring anti-arrhythmic therapy (beta blockers or
digoxin are permitted);

- Uncontrolled hypertension (systolic blood pressure > 150 mmHg or diastolic blood
pressure > 90 mmHg) despite optimal medical management

3. Past or concurrent history of neoplasm < 5 years prior to start of study treatment
other than gastric adenocarcinoma or gastroesophageal junction adenocarcinoma, except
for curatively treated non-melanoma skin cancer, in situ carcinoma of the cervix
uteri or superficial bladder tumors [Ta noninvasive tumor (Ta), carcinoma in situ
(Tis) and T1 (tumor invades lamina propria)]

4. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to randomization

5. Evidence of gastrointestinal perforation or bowel obstruction during the screening

6. Evidence or history of bleeding diathesis or coagulopathy

7. Non-healing wound, ulcer, or bone fracture

8. History of gastrointestinal bleeding > grade 1 CTCAE version 4.0 within 4 weeks prior
to randomization

9. History of any other bleeding > grade 2 according to CTCAE version 4.0 within 4 weeks
prior to randomization

10. Known psychiatric and neurological disorders including known peripheral or autonomous
neuropathy or hearing impairment > grade 1 according to CTCAE version 4.0

- However, if the patient already has known irreversible grade 4 hearing loss (>90
decibels (dB) bilaterally) at baseline, he or she is eligible at the
investigator's discretion

11. Pregnant or lactating women, women of childbearing potential not employing adequate
contraception [Women of childbearing potential must have a negative serum pregnancy
test performed within seven days prior to the start of treatment. Of note, both men
and women enrolled in this trial must use adequate barrier birth control measures
during the course of the trial and four weeks after the completion of trial or 6
months after last dose of cisplatin (whichever is greater). The definition of
effective contraception will be based on the clinical judgment of the principal
investigator or a designated associate.]

12. Evidence of infection (> grade 2 )

13. History of HIV infection or chronic / active hepatitis B or C

14. Evidence of brain metastasis. Patients with unexplained neurological symptoms will
undergo a CT scan or MRI of the brain to exclude metastases.

15. Seizure disorder requiring treatment with medications that affect CYP 3A4

16. History of organ allograft

17. Known or suspected allergy or hypersensitivity to any of the study drugs, study drug
classes or excipients in the formulation given during the course of this trial

18. Any condition that is unstable or could jeopardize the safety of the patient and his
/ her compliance in the study

19. Inability to swallow or retain oral medications

20. Any malabsorption condition that the investigator deems would jeopardize the
absorption or pharmacokinetics of the study medication

21. Uncorrected dehydration

22. Known dihydropyrimidine dehydrogenase deficiency

23. Substance abuse, medical, psychological or social conditions that may interfere with
the patient's participation in the study or evaluation of the study results

24. Evidence of thrombotic or embolic disease, including cerebrovascular accident,
transient ischemic attacks, or pulmonary embolus within the past 6 months

25. Any tumor with characteristics that the investigator deems unsuitable for potentially
cytoreductive therapy due to likelihood of severe bleeding or perforation such as
ulcerations or hemorrhage. Excluded therapies and medications

26. Prior or concomitant systemic anticancer therapy including cytotoxic therapy,
targeted agents, or experimental therapy for gastric cancer. However, (neo)-adjuvant
cytotoxic therapy is permitted if the last dose was administered > 6 months (12
months for platinum based therapy) before start of study medication in this study.

27. Radiotherapy prior to or during the study (palliative radiotherapy will be allowed as
described in the 'prior and concomitant therapy section',4.3.7)

28. Use of biologic response modifiers, such as granulocyte G-CSF, within 3 weeks of
study entry and during the study.

29. Investigational drug therapy outside of this trial during or within 4 weeks prior to

30. Previous exposure to a Ras pathway inhibitor such MEK or Raf inhibitors or any
farnesyl transferase inhibitors

31. Therapeutic anticoagulation with vitamin K antagonists such as warfarin, or with
heparins or heparinoids

- Low dose warfarin (1 mg p.o. q.d.) is permitted if the international normalized
ratio is < 1.5

- Low-dose aspirin is permitted (≤ 100 mg daily)

- Prophylactic doses of heparin are permitted

- For patients on warfarin, the INR will be measured prior to initiation of
sorafenib, and patients will be monitored regularly for changes in prothrombin
time, INR or clinical bleeding episodes as infrequent bleeding or elevations in
the INR have been reported in some patients taking warfarin while on sorafenib

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Kang Yoon-Koo, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Asan Medical Center


Korea: Food and Drug Administration

Study ID:




Start Date:

August 2010

Completion Date:

August 2013

Related Keywords:

  • Malignant Neoplasm of Stomach
  • Effects of Chemotherapy
  • First line chemotherapy in advanced gastric cancer
  • Neoplasms
  • Stomach Neoplasms