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Sorafenib, Docetaxel, and Cisplatin in Treating Patients With Metastatic or Advanced Gastric or Gastroesophageal Junction Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00253370
Recruitment Status : Completed
First Posted : November 15, 2005
Results First Posted : November 24, 2014
Last Update Posted : November 24, 2014
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase II trial is studying how well giving sorafenib together with docetaxel and cisplatin works in treating patients with metastatic or locally advanced gastric or gastroesophageal junction cancer that cannot be removed by surgery. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as docetaxel and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sorafenib together with docetaxel and cisplatin may kill more tumor cells.

Condition or disease Intervention/treatment Phase
Adenocarcinoma of the Gastroesophageal Junction Metastatic Gastric Cancer Advanced Unresectable Gastric Cancer Drug: BAY 43-9006 Drug: docetaxel Drug: cisplatin Phase 2

Detailed Description:


I. To evaluate the response rate (complete response and partial response) of the combination of BAY 43-9006 with docetaxel and cisplatin or oxaliplatin in patients with gastric and GEJ adenocarcinoma.

II. To evaluate the progression-free survival (PFS) and overall survival.

III. To evaluate the toxicities of BAY 43-9006 in patients with advanced and metastatic gastric or GEJ adenocarcinoma combined with docetaxel/cisplatin or docetaxel/oxaliplatin.

IV. To evaluate Raf status in the tumor and to correlate response and PFS to the presence or absence of an activating mutation in B-Raf.

V. To analyze the pharmacokinetic and pharmacogenetic properties of BAY 43-9006 including angiogenesis, monooxygenases, polymorphisms and multidrug-resistance (MDR). This study will be conducted via the E1Y03 mechanism.

OUTLINE: This is an open-label, multicenter study. Patients are stratified according to Siewert's tumor location (I vs II vs III) and extent of disease (locally advanced unresectable vs distant metastases).

Patients receive oral BAY 43-9006 twice daily on days 1-21. Patients also receive docetaxel intravenously (IV) over 1 hour and cisplatin IV over 1-2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 3 years.

An addition of an arm containing oxaliplatin was proposed after meeting the accrual goal but did not move forward and the study was closed to accrual in July, 2007 with a final accrual of 44 patients.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study to Evaluate Overall Response Rate of BAY 43-9006 (Sorafenib) Combined With Docetaxel and Cisplatin or Oxaliplatin in the Treatment of Metastatic or Advanced Unresectable Gastric and Gastroesophageal Junction (GEJ) Adenocarcinoma
Study Start Date : October 2005
Actual Primary Completion Date : May 2008
Actual Study Completion Date : September 2010

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: BAY 43-9006, docetaxel, cisplatin
Patients receive oral BAY 43-9006 400mg twice daily on days 1-21. Patients also receive docetaxel IV, 75 mg/m2 over 1 hour and cisplatin IV, 75 mg/m2 over 1-2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: BAY 43-9006
Given orally
Other Names:
  • Sorafenib (NSC724772)
  • BAY 54-9085 (tosylate salt)

Drug: docetaxel
Given IV
Other Names:
  • Taxotere
  • RP 56976
  • NSC #628503

Drug: cisplatin
Given IV
Other Names:
  • Cis-diaminedichloroplatinum
  • Cis-diaminedichloroplatinum (II)
  • diaminedichloroplatinum
  • cis-platinum
  • platinum
  • Platinol
  • Platinol-AQ
  • DDP
  • CDDP
  • DACP
  • NSC 119875.

Primary Outcome Measures :
  1. The Proportion of Patients With Objective Response (Complete Response or Partial Response) [ Time Frame: Assessed every 6 weeks until disease progression or up to 3 years ]
    Response was evaluated using RECIST (Response Evaluation Criteria in Solid Tumors) 1.0 criteria. Per RECIST criteria, complete response (CR) = disappearance of all target and non-target lesions. Partial response (PR)= >=30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits. Objective response = CR + PR.

Secondary Outcome Measures :
  1. Progression-free Survival (PFS) [ Time Frame: Assessed every 6 weeks until disease progression or up to 3 years ]

    Progression-free survival was defined as the shorter of:

    1. The time from registration to progression. or
    2. The time from registration to death without documentation of progression given that the death occurs within 4 months of the last disease assessment without progression (or registration, whichever is more recent).

    Therefore, cases not meeting either of the criteria for a PFS event are censored at the date of last disease assessment without progression (or registration, whichever is more recent).

    Progression is defined as at least 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s) or unequivocal progression of existing non-target lesions.

  2. Overall Survival (OS) [ Time Frame: Assessed every 3 months if patient is < 2 years from study entry; then every 6 months if patient is 2-3 years from study entry. ]
    Overall survival was defined as the time from registration to death from any cause.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients must have measurable, histologically confirmed, advanced unresectable or metastatic gastric or GEJ adenocarcinoma; imaging studies must be conducted within 4 weeks of study entry
  • For patients with GEJ adenocarcinoma, the tumor location should be specified using the Siewert classification used in other NCI-sponsored Phase II studies in these disease sites
  • Patients must have an ECOG performance status of 0-1
  • Patients may have had adjuvant chemotherapy or chemoradiation therapy, with or without 5-Fluorouracil if the treatment was performed more than 6 months before any evidence of recurrent or metastatic disease
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Must have the following baseline laboratory values obtained within 2 weeks of registration:

    • Absolute Granulocyte Count >= 1,500/mm^3
    • Platelet Count >= 100,000/mm^3
    • White Blood Count >= 3,000/mm^3
    • Serum Creatinine <= 1.5 mg/dl
    • Total Bilirubin <= 2.0 mg/dl
    • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/alkaline phosphatase (Alk phos) <= 2.5 x upper limit of normal
  • Patients must be able to take oral medication without crushing, dissolving or chewing tablets

Exclusion Criteria:

  • Prior radiotherapy, chemotherapy or investigational therapies, particularly inhibitors of tyrosine Kinases, signal transduction or angiogenesis in the treatment for their recurrent and/or metastatic gastric or GEJ adenocarcinoma
  • Receiving any other investigational agents
  • Being pregnant or breast-feeding; all females of childbearing potential must have a blood or urine test within 2 weeks prior to registration to rule out pregnancy
  • HIV-positive patients receiving combination antiretroviral therapy are excluded from the study because of possible pharmacokinetic interactions with BAY 43-9006
  • Brain metastases
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to BAY 43-9006
  • Acute active infection with significant clinical intervention per physician's discretion
  • Previous or concurrent malignancies are not allowed, except:

    • Non-melanoma skin cancer and in situ cervical cancer
    • Treated cancer from which the patient has been continuously disease-free for more than five years
  • Other uncontrolled intercurrent illnesses including, but not limited to: uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/addictive disorders that would limit compliance with study requirements
  • Evidence of bleeding diathesis
  • Concurrent cytochrome P450 enzyme-inducing anti-epileptic drugs:

    • Phenytoin
    • Carbamazepine
    • Phenobarbital
    • Rifampin
    • St. John's Wort

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00253370

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United States, Massachusetts
Eastern Cooperative Oncology Group
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
National Cancer Institute (NCI)
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Study Chair: Weijing Sun, MD University of Pennsylvania

Publications of Results:
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Responsible Party: National Cancer Institute (NCI) Identifier: NCT00253370     History of Changes
Other Study ID Numbers: NCI-2012-02951
NCI-2012-02951 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
E5203 ( Other Identifier: Eastern Cooperative Oncology Group (ECOG) )
U10CA021115 ( U.S. NIH Grant/Contract )
First Posted: November 15, 2005    Key Record Dates
Results First Posted: November 24, 2014
Last Update Posted: November 24, 2014
Last Verified: December 2013
Keywords provided by National Cancer Institute (NCI):
gastric cancer
gastroesophageal junction adenocarcinoma
Additional relevant MeSH terms:
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Stomach Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors