Sorafenib. ICORG 06-41, V4

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
ICORG- All Ireland Cooperative Oncology Research Group
ClinicalTrials.gov Identifier:
NCT01158287
First received: July 7, 2010
Last updated: January 22, 2014
Last verified: January 2014
  Purpose

RATIONALE: Sorafenib tosylate 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.

PURPOSE: This phase II trial is studying how well sorafenib tosylate works in treating patients with relapsed esophageal cancer and/or stomach cancer.


Condition Intervention Phase
Esophageal Cancer
Gastric Cancer
Drug: sorafenib tosylate
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Single Agent Sorafenib in the Treatment of Relapsed Esophageal/Gastric Adenocarcinoma in Platinum Pre-Treated Patients

Resource links provided by NLM:


Further study details as provided by ICORG- All Ireland Cooperative Oncology Research Group:

Primary Outcome Measures:
  • Disease control rate after 4 months [ Time Frame: After 4 months of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: Ongoing ] [ Designated as safety issue: No ]

    Progression free survival and overall survival probabilities over time will be estimated using Kaplan-Meier plots. Their medians with their confidence intervals will be also presented.

    Progression Free Survival is measured from first treatment until the date of disease progression or death, whichever is reported first. Subjects who do not progress or die at the time of the analysis will be censored at the day of their last tumour assessment.


  • Overall survival [ Time Frame: Ongoing ] [ Designated as safety issue: No ]
    Overall survival is measured from the date of first treatment to the date of the subject's death. If the subject is alive or the vital status is unknown, the date of death will be censored at the date that the subject is last known to be alive.

  • Time to tumor progression [ Time Frame: Ongoing ] [ Designated as safety issue: No ]
  • Objective response rate [ Time Frame: Response would be assessed by appropriate imaging (e.g. CT) every 8 weeks. ] [ Designated as safety issue: No ]
    The study has been designed to use the disease control rate at 4 months on treatment as the primary endpoint.

  • Tolerability and toxicity [ Time Frame: Ongoing for duration of treatment and 30 day follow up. ] [ Designated as safety issue: Yes ]
    Patients would be assessed for toxicity according to NCI CTC version 3.


Estimated Enrollment: 54
Study Start Date: February 2009
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sorafenib 400mg bd, p.o, continuously Drug: sorafenib tosylate Other: laboratory biomarker analysis

Detailed Description:

OBJECTIVES:

Primary

  • To determine the disease control rate (complete response, partial response, and stable disease) of sorafenib tosylate after 4 months in patients with relapsed esophageal or gastric adenocarcinoma previously treated with platinum-based chemotherapy.

Secondary

  • To determine the progression-free survival of patients treated with this drug.
  • To determine the overall survival of patients treated with this drug.
  • To determine the time to tumor progression in patients treated with this drug.
  • To determine the objective response rate in patients treated with this drug.
  • To determine the tolerability and toxicity in patients treated with this drug.
  • To assess biomarkers associated with response/resistance to therapy. (exploratory)

OUTLINE: This is a multicenter study.

Patients receive oral sorafenib tosylate twice a day on days 1-28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

Blood and tumor samples may be collected periodically and analyzed for biological markers.

After completion of study treatment, patients are followed up periodically.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed esophageal and/or gastric adenocarcinoma

    • Relapsed or progressed disease after prior platinum-based chemotherapy and not a suitable candidate for radical therapy
  • At least 1 unidimensionally measurable lesion as assessed by RECIST criteria
  • No uncontrolled, symptomatic brain metastases

    • Patients with intracranial bleeding into metastases allowed provided the disease is well-controlled and not undergoing acute steroid therapy or taper (chronic steroid therapy allowed provided the dose is stable for 1 month prior to and following screening radiographic studies)

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Life expectancy ≥ 2 months
  • Hemoglobin ≥ 9.0 g/dL
  • Absolute neutrophil count ≥ 1.5 x 10^9/L
  • Platelet count ≥ 100 x 10^9/L
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT/AST ≤ 2.5 times ULN (≤ 5 times ULN for patients with liver involvement)
  • Alkaline phosphatase ≤ 2.5 times ULN (≤ 4 times ULN for patients with bony involvement)
  • INR ≤ 1.5
  • aPTT normal
  • Creatinine ≤ 1.5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier method contraception prior to and during study therapy (men and women) and for 3 months after completion of study therapy (men)
  • Not planning pregnancy within 6 months after completion of study therapy
  • No history of cardiac disease, including any of the following:

    • NYHA class III-IV congestive heart failure
    • Active coronary artery disease (myocardial infarction more than 6 months prior to study entry allowed)
    • Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
  • No uncontrolled hypertension (systolic BP > 150 mm Hg or diastolic BP > 90 mm Hg, despite optimal medical management)
  • No known HIV infection or chronic hepatitis B or C
  • No active, clinically serious infections > CTCAE grade 2
  • No thrombotic or embolic events (e.g., cerebrovascular accident including transient ischemic attacks within the past 6 months)
  • No pulmonary hemorrhage or bleeding event > CTCAE grade 2 within the past 4 weeks
  • No other hemorrhage or bleeding event > CTCAE grade 3 within the past 4 weeks
  • No serious, nonhealing wound, ulcer (apart from the tumor), or bone fracture
  • No evidence or history of bleeding diathesis or coagulopathy
  • No current signs or symptoms of severe progressive or uncontrolled hepatic, hematological, renal, endocrine, pulmonary, or cardiac disease
  • No known or suspected allergy to sorafenib or any agent given in the course of this trial
  • No previous cancer that is distinct in primary site or histology from esophago-gastric junction cancer except for carcinoma in situ of the cervix, treated basal cell carcinoma, superficial bladder tumors [Ta and Tis], or any cancer curatively treated > 3 years prior to study entry
  • No concurrent cancer that is distinct in primary site or histology from esophago-gastric cancer
  • No substance abuse, medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
  • No condition that impairs the patient's ability to swallow whole pills
  • No malabsorption condition
  • No seizure disorder requiring medication (e.g., steroids or antiepileptics)
  • No familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
  • No significant traumatic injury within the past 4 weeks

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 3 weeks since prior local radiotherapy
  • At least 3 weeks since prior biologic response modifiers (e.g., G-CSF)

    • G-CSF and other hematopoietic growth factors allowed in the management of acute toxicity (e.g., febrile neutropenia) when clinically indicated or at the discretion of the investigator, however they may not be substituted for a required dose reduction
    • Concurrent chronic erythropoietin allowed provided no dose adjustment is undertaken within 2 months prior to the study or during the study
  • At least 4 weeks since prior major surgery or open biopsy
  • At least 4 weeks since prior and no concurrent radiotherapy

    • Prior or concurrent palliative radiotherapy to symptomatic disease sites allowed (unless the site to be irradiated is one of the target lesions used for response assessment)
  • At least 4 weeks since prior and no concurrent anticancer chemotherapy, immunotherapy, or hormonal therapy (except bisphosphonates)
  • At least 30 days since prior and no concurrent investigational drug therapy
  • At least 5 weeks since prior and no concurrent mitomycin C or nitrosoureas
  • At least 4 months since prior autologous bone marrow transplant or stem cell rescue
  • No history of organ allograft
  • No prior licensed or investigational tyrosine kinase inhibitor or antiangiogenic agent (e.g., sunitinib or bevacizumab)
  • No prior sorafenib tosylate
  • No prior licensed or investigational drug treatment that targets the RAS, VEGF, VEGFR, or EGFR pathway
  • No concurrent rifampin or St. John wort
  • No concurrent therapeutic anticoagulation with vitamin K antagonists (e.g., warfarin, heparins, or heparinoids)

    • Low-dose warfarin (1 mg by mouth once a day) allowed provided INR is < 1.5
    • Low-dose aspirin allowed
  • No concurrent renal dialysis
  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: NCT01158287

Locations
Ireland
Cork University Hospital
Cork, Ireland
Bon Secours Hospital
Cork, Ireland
Adelaide and Meath Hospital, Dublin Incorporating the National Children's Hospital
Dublin, Ireland, 24
Beaumont Hospital
Dublin, Ireland, 9
Mater Misericordiae University Hospital
Dublin, Ireland, 7
St. James's Hospital
Dublin, Ireland, 8
University College Hospital
Galway, Ireland
Waterford Regional Hospital
Waterford, Ireland
Sponsors and Collaborators
ICORG- All Ireland Cooperative Oncology Research Group
Investigators
Principal Investigator: Kenneth O'Byrne, MD St. James's Hospital, Ireland
  More Information

Additional Information:
No publications provided

Responsible Party: ICORG- All Ireland Cooperative Oncology Research Group
ClinicalTrials.gov Identifier: NCT01158287     History of Changes
Other Study ID Numbers: CDR0000680617, ICORG-06-41, EUDRACT-2008-005062-31, EU-21045
Study First Received: July 7, 2010
Last Updated: January 22, 2014
Health Authority: Ireland: Irish Medicines Board

Keywords provided by ICORG- All Ireland Cooperative Oncology Research Group:
adenocarcinoma of the esophagus
recurrent esophageal cancer
recurrent gastric cancer
adenocarcinoma of the stomach

Additional relevant MeSH terms:
Adenocarcinoma
Esophageal Neoplasms
Stomach Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Stomach Diseases
Sorafenib
Niacinamide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 27, 2014