Sorafenib. ICORG 06-41, V4

Study Description

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Brief Summary:

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 or disease	Intervention/treatment	Phase
Esophageal Cancer; Gastric Cancer	Drug: sorafenib tosylate; Other: laboratory biomarker analysis	Phase 2

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	54 participants
Intervention Model:	Single Group Assignment
Masking:	None (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
Study Start Date :	February 2009
Actual Primary Completion Date :	November 2012

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Sorafenib 400mg bd, p.o, continuously	Drug: sorafenib tosylate; Other: laboratory biomarker analysis

Outcome Measures

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Primary Outcome Measures :

1. Disease control rate after 4 months [ Time Frame: After 4 months of treatment ]

Secondary Outcome Measures :

1. Progression-free survival [ Time Frame: Ongoing ]

   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.

2. Overall survival [ Time Frame: Ongoing ]
   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.
3. Time to tumor progression [ Time Frame: Ongoing ]
4. Objective response rate [ Time Frame: Response would be assessed by appropriate imaging (e.g. CT) every 8 weeks. ]
   The study has been designed to use the disease control rate at 4 months on treatment as the primary endpoint.
5. Tolerability and toxicity [ Time Frame: Ongoing for duration of treatment and 30 day follow up. ]
   Patients would be assessed for toxicity according to NCI CTC version 3.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
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

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Locations

Ireland
Bon Secours Hospital
Cork, Ireland
Cork University Hospital
Cork, Ireland
Adelaide and Meath Hospital, Dublin Incorporating the National Children's Hospital
Dublin, Ireland, 24
Mater Misericordiae University Hospital
Dublin, Ireland, 7
St. James's Hospital
Dublin, Ireland, 8
Beaumont Hospital
Dublin, Ireland, 9
University College Hospital
Galway, Ireland
Waterford Regional Hospital
Waterford, Ireland

Sponsors and Collaborators

Cancer Trials Ireland

Investigators

Principal Investigator:	Kenneth O'Byrne, MD	St. James's Hospital, Ireland

More Information

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Responsible Party:	Cancer Trials Ireland
ClinicalTrials.gov Identifier:	NCT01158287 History of Changes
Other Study ID Numbers:	06-41 ICORG; ICORG-06-41; EUDRACT-2008-005062-31; EU-21045
First Posted:	July 8, 2010
Last Update Posted:	December 31, 2014
Last Verified:	January 2014

Keywords provided by Cancer Trials Ireland:

adenocarcinoma of the esophagus; recurrent esophageal cancer; recurrent gastric cancer; adenocarcinoma of the stomach

Additional relevant MeSH terms:

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