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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00253370
First received: November 11, 2005
Last updated: November 19, 2014
Last verified: December 2013
  Purpose

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

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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:
  • Progression-free Survival (PFS) [ Time Frame: Assessed every 6 weeks until disease progression or up to 3 years ] [ Designated as safety issue: No ]

    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.


  • 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. ] [ Designated as safety issue: No ]
    Overall survival was defined as the time from registration to death from any cause.


Enrollment: 44
Study Start Date: October 2005
Study Completion Date: September 2010
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Detailed Description:

PRIMARY OBJECTIVES:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00253370

Locations
United States, Massachusetts
Eastern Cooperative Oncology Group
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Investigators
Study Chair: Weijing Sun, MD University of Pennsylvania
  More Information

Additional Information:
Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00253370     History of Changes
Other Study ID Numbers: NCI-2012-02951, NCI-2012-02951, E5203, U10CA021115
Study First Received: November 11, 2005
Results First Received: May 21, 2014
Last Updated: November 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
Sorafenib
Docetaxel
Cisplatin
gastric cancer
gastroesophageal junction adenocarcinoma

Additional relevant MeSH terms:
Adenocarcinoma
Esophageal Neoplasms
Stomach Neoplasms
Carcinoma
Digestive System Diseases
Digestive System Neoplasms
Esophageal Diseases
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Head and Neck Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Stomach Diseases
Cisplatin
Docetaxel
Sorafenib
Antimitotic Agents
Antineoplastic Agents
Enzyme Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Radiation-Sensitizing Agents
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on November 24, 2014