Sorafenib. ICORG 06-41, V4

Cancer Trials Ireland

Status and phase

Completed

Phase 2

Conditions

Gastric Cancer

Esophageal Cancer

Treatments

Other: laboratory biomarker analysis

Drug: sorafenib tosylate

Study type

Interventional

Funder types

NETWORK

Identifiers

NCT01158287

06-41 ICORG

EUDRACT-2008-005062-31

EU-21045

ICORG-06-41

Details and patient eligibility

About

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.

Full 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.

Enrollment

54 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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