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Sorafenib Tosylate in Treating Patients With Progressive Metastatic Neuroendocrine Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00131911
First received: August 16, 2005
Last updated: November 14, 2014
Last verified: June 2014
  Purpose

This phase II trial is studying how well sorafenib tosylate works in treating patients with progressive metastatic neuroendocrine tumors. 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.


Condition Intervention Phase
Gastrinoma
Glucagonoma
Insulinoma
Metastatic Gastrointestinal Carcinoid Tumor
Neuroendocrine Tumor
Pancreatic Polypeptide Tumor
Recurrent Gastrointestinal Carcinoid Tumor
Recurrent Islet Cell Carcinoma
Somatostatinoma
WDHA Syndrome
Drug: sorafenib tosylate
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Bay 43-9006 in Progressive Metastatic Neuroendocrine Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Confirmed Response Rate [ Time Frame: Duration of Treatment (Up to 2 years) ] [ Designated as safety issue: No ]

    Confirmed response rate was defined using Response Evaluation Criteria In Solid Tumors (RECIST). A confirmed response is defined as a complete response (CR) or partial response (PR) observed on subsequent scans at least 4 weeks apart. Confirmed response rate was estimated by the number of successes divided by the total number of evaluable patients.

    >

    > Complete Response (CR) is defined as the disappearance of all target lesions.

    > Partial Response (PR) is defined as a 30% decrease in sum of longest diameter of target lesions;

    >

    > We report the percentage of patients with a confirmed response and a 95% confidence interval estimated by the Duffy and Santner method.



Secondary Outcome Measures:
  • Toxicity [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    For this secondary endpoint, toxicity is defined as a grade 3 or higher adverse events that is classified as either possibly, probably, or definitely related to study treatment. The assignment of attribution to study treatment and grade (or degree of severity) of the adverse event are classified using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The number of participants reporting a grade 3 or higher toxicity are reported.

  • Overall Survival [ Time Frame: From registration to death (up to 2 years) ] [ Designated as safety issue: No ]
    Overall survival (OS) was defined as the time from registration to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% CI was estimated using the Kaplan Meier method.

  • Progression Free Survival [ Time Frame: Time from registration to progression or death (up to 2 years) ] [ Designated as safety issue: No ]
    Progression was defined using Response Evaluation Criteria In Solid Tumors (RECIST) as a 20% increase in the su of longest diameter of target lesions. Progression free survival (PFS) was defined as the time from registration to progression or death of any cause. Participants who were progression free were censored at the date of their most recent disease assessment. The median PFS with 95% CI was estimated using the Kaplan Meier method.

  • Duration of Response [ Time Frame: Time from response to progression (up to 2 years) ] [ Designated as safety issue: No ]
    Duration of response (DOR) was defined as the time from attaining a response (PR or CR) to the date of progression. Participants without progression were censored at the date of their most recent disease assessment. The median DOR was estimated using simple summary statistics.


Enrollment: 93
Study Start Date: June 2005
Study Completion Date: April 2013
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A (patients with carcinoid tumors)
Patients receive 400 mg oral sorafenib twice daily on days 1-28.
Drug: sorafenib tosylate
400 mg given orally
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN
Experimental: Group B (islet cell and other neuroendocrine tumors)
Patients receive 400 mg oral sorafenib twice daily on days 1-28.
Drug: sorafenib tosylate
400 mg given orally
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the objective tumor response rate of BAY 43-9006 (sorafenib tosylate) in patients with advanced neuroendocrine tumors.

SECONDARY OBJECTIVES:

I. Adverse event rate(s). II. Progression free survival and time to progression. III. Improvement in circulating hormone levels. IV. Overall survival.

OUTLINE: This is a multicenter study. Patients are grouped into 2 separate analysis Groups according to tumor type (Group A: Carcinoid; Group B: Islet cell/other well-differentiated tumor). Each Group was independently evaluated for all study endpoints.

Patients receive oral sorafenib tosylate 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.

  Eligibility

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

Criteria:

  • 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
  • Performance status:

    • Eastern Cooperative Oncology Group (ECOG) 0-2
  • Life expectancy:

    • At least 24 weeks
  • Hematopoietic:

    • Absolute neutrophil count >= 1,500/mm3
    • Platelet count >= 100,000/mm3
    • No bleeding diathesis
  • Hepatic:

    • Bilirubin =< 2 times upper limit of normal (ULN)
    • Aspartate aminotransferase (AST) =< 3 times ULN (5 times ULN if liver metastases are present)
    • International normalized ratio (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
  • 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
  • At least 4 weeks since prior interferon
  • No more than 1 prior systemic chemotherapy regimen:

Chemoembolization is not considered systemic chemotherapy

  • At least 4 weeks since prior chemoembolization
  • At least 3 weeks since prior radiotherapy
  • No prior procedures adversely affecting intestinal absorption
  • 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)
  • Prior or concurrent octreotide for symptomatic treatment allowed
  • 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

  • At least 4 weeks since prior major surgery
  • Recovered from all prior therapy
  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: NCT00131911

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Investigators
Principal Investigator: Timothy Hobday Mayo Clinic
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00131911     History of Changes
Other Study ID Numbers: NCI-2009-00121, MC044H, 7046, CDR0000437792, N01CM62205
Study First Received: August 16, 2005
Results First Received: June 19, 2014
Last Updated: November 14, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Gastrinoma
Carcinoid Tumor
Carcinoma, Islet Cell
Gastrointestinal Neoplasms
Glucagonoma
Insulinoma
Malignant Carcinoid Syndrome
Neoplasms
Neuroendocrine Tumors
Somatostatinoma
Adenocarcinoma
Adenoma
Adenoma, Islet Cell
Carcinoma
Carcinoma, Neuroendocrine
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Gastrointestinal Diseases
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Pancreatic Diseases
Pancreatic Neoplasms
Niacinamide
Sorafenib

ClinicalTrials.gov processed this record on November 25, 2014