Sorafenib in Treating Patients With Angiosarcoma That is Locally Advanced, Metastatic, or Unable to Be Removed by Surgery

Centre Oscar Lambret

Status and phase: Unknown; Phase 2

Conditions: Sarcoma

Treatments: Drug: sorafenib tosylate

Study type: Interventional

Funder types: Other

Identifiers

NCT00874874

COL-Angio-Next

CDR0000633547

INCA-RECF0636

COL-2007-10

BAYER-COL-Angio-Next

EUDRACT-2007-004651-10

Details and patient eligibility

About

RATIONALE: 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.

PURPOSE: This phase II trial is studying how well sorafenib works in treating patients with angiosarcoma that is locally advanced, metastatic, or unable to be removed by surgery.

Full description

OBJECTIVES:

Primary

Determine the rate of non-progression at 9 months in patients with unresectable, locally advanced, or metastatic angiosarcoma treated with sorafenib tosylate.

Secondary

Determine the rate of non-progression at 60, 120, and 180 days. Determine the median time to progression. Determine overall survival. Determine the best response rate. Determine the clinical and biological factors that predict clinical benefit. Evaluate tolerability by NCI CTCAE v3.0. Correlate efficacy with plasma expression of genes implicated in controlling angiogenesis. Explore the tumor expression of these genes in tissue from a tumor bank.

OUTLINE: This is a multicenter study.

Patients are stratified according to disease type (cutaneous angiosarcoma [scalp, breast, or soft tissue] vs visceral angiosarcoma). All patients receive oral sorafenib tosylate twice daily for 9 months in the absence of disease progression or unacceptable toxicity.

Enrollment: 96 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed angiosarcoma

  • Locally advanced or metastatic disease
  • Unresectable disease

• No Kaposi sarcoma, hemangiopericytoma, or hemangioendothelioma

• Measurable tumor with at least 1 measurable lesion by RECIST criteria

• Tumor in a previously irradiated area must not show progression

• No brain metastases or meningeal tumors (symptomatic or asymptomatic)

PATIENT CHARACTERISTICS:

• WHO performance status 0-2

• Life expectancy ≥ 3 months

• WBC ≥ 3,000/mm³

• ANC ≥ 1,500/mm³

• Platelet count ≥ 100,000/mm³

• Hemoglobin ≥ 9 g/dL

• PT or INR and aPTT ≤ 1.5 times upper limit of normal (ULN)

  • Anticoagulation treatment with heparin or vitamin K allowed if the above criteria are met

• Liver transaminases ≤ 2.5 times ULN (≤ 5 times ULN in the presence of liver metastases)

• Total bilirubin ≤ 1.5 times ULN

• Serum creatinine ≤ 1.5 times ULN

• Amylase and lipase ≤ 1.5 times ULN

• Not pregnant or nursing

• Weight loss from pre-disease weight < 20% over the past 12 months

• Able to swallow

• No active or ischemic coronary artery disease

• No myocardial infarction within the past 6 months

• No NYHA class III-IV cardiac failure

• No uncontrolled hypertension

• No coagulopathy

• No active uncontrolled peptic ulcer

• No patients on renal dialysis

• No active bacterial or fungal infection > CTCAE v3.0 grade 2

• No HIV or hepatitis B or C positivity

• No chronic unstable illness that could jeopardize patient safety or compliance

• No other progressive or malignant tumor

• No known or suspected allergy to sorafenib tosylate

• No psychological, familial, social, or geographic situations that preclude clinical follow up

• No patients deprived of liberty or under guardianship

• No cardiac arrhythmia requiring antiarrhythmic medication (except beta-blockers or digoxin for chronic atrial fibrillation)

• No epilepsy requiring antiepileptic drugs

PRIOR CONCURRENT THERAPY:

• See Patient Characteristics
• No prior organ or peripheral stem cell transplantation
• No more than 2 prior lines of chemotherapy
• At least 28 days since prior treatment (systemic or major surgery)
• No concurrent therapy for another malignancy
• No concurrent CYP3A inducers (e.g., rifampicin, St. John wort, phenytoin, carbamazepine, phenobarbital, dexamethasone)