Sorafenib in Treating Patients With Progressive Metastatic Neuroendocrine Tumors

Official Title: “A Phase II Trial of Bay 43-9006 in Progressive Metastatic Neuroendocrine Tumors”

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 progressive metastatic neuroendocrine tumors.

OBJECTIVES:

Primary - Determine the objective tumor response rate in patients with progressive metastatic neuroendocrine tumors treated with sorafenib.

Secondary - Determine the adverse event rate in patients treated with this drug. - Determine time to progression and progression-free and overall survival of patients treated with this drug. - Determine improvement in circulating hormone levels in patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to tumor type (carcinoid vs islet cell/other well-differentiated tumor).

Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months until disease progression and then every 6 months for up to 2 years from study entry.

PROJECTED ACCRUAL: Approximately 38-90 patients (22-46 with carcinoid tumors and 12-39 with islet cell carcinoma/other well-differentiated tumors) will be accrued for this study within 3.2-7.5 months.

Intervention(s) in this Clinical Trial

• Drug: sorafenib tosylate

Primary Measures

• Confirmed response rate
  • Safety Issue?: No

Secondary Measures

• Toxicity
  • Safety Issue?: Yes
• Biochemical levels and response
  • Safety Issue?: No
• Survival time
  • Safety Issue?: No
• Time to disease progression
  • Safety Issue?: No
• Duration of response
  • Safety Issue?: No
• Time to treatment failure
  • Safety Issue?: No

DISEASE CHARACTERISTICS:

• Histologically confirmed neuroendocrine tumor
• Carcinoid tumor OR islet cell carcinoma/other well-differentiated tumor
• No anaplastic or high-grade histology
• Metastatic disease
• Measurable disease
• No thyroid carcinoma of any histology, thymoma, or pheochromocytoma/paraganglioma
• No known brain metastases

PATIENT CHARACTERISTICS:

• Age
• 18 and over
• Performance status
• ECOG 0-2
• Life expectancy
• At least 24 weeks
• Hematopoietic
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• No bleeding diathesis
• Hepatic
• Bilirubin ≤ 2 times upper limit of normal (ULN)
• AST ≤ 3 times ULN (5 times ULN if liver metastases are present)
• INR normal
• PTT normal
• Renal
• Creatinine ≤ 1.5 times ULN
• Cardiovascular
• No poorly controlled hypertension
• No symptoms of congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• Gastrointestinal
• Able to swallow capsules intact
• No gastrointestinal tract disease resulting in an inability to take oral medication (e.g., dysphagia)
• No requirement for IV alimentation
• No active peptic ulcer disease
• Other
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No other invasive malignancy within the past 3 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No other uncontrolled illness

PRIOR CONCURRENT THERAPY:

• Biologic therapy
• At least 4 weeks since prior interferon
• Chemotherapy
• No more than 1 prior systemic chemotherapy regimen
• Chemoembolization is not considered systemic chemotherapy
• At least 4 weeks since prior chemoembolization
• Endocrine therapy
• Prior or concurrent octreotide for symptomatic treatment allowed
• Radiotherapy
• At least 3 weeks since prior radiotherapy
• Surgery
• At least 4 weeks since prior major surgery
• No prior procedures adversely affecting intestinal absorption
• Other
• Recovered from all prior therapy
• At least 4 weeks since prior hepatic artery embolization
• No other prior systemic therapy
• No other concurrent investigational treatment
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent enzyme-inducing anticonvulsants (e.g., carbamazepine, phenobarbital, or phenytoin)
• No concurrent rifampin
• No concurrent Hypericum perforatum (St. John's wort)
• No concurrent therapeutic anticoagulation
• Concurrent prophylactic anticoagulation (i.e., low dose warfarin) of venous or arterial access devices allowed provided requirements for INR or PTT are met

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Mayo Clinic Other

Overall Clinical Trial Officials and Contacts

Timothy Hobday, MD Study Chair Mayo Clinic  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00131911

Study ID Number: CDR0000437792

ClinicalTrials.gov Identifier: NCT00131911

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database