CompletedNCT00131911Updated Nov 17, 2014Results posted

Sorafenib Tosylate in Treating Patients With Progressive Metastatic Neuroendocrine Tumors

A Phase 2 interventional study of sorafenib tosylate in Gastrinoma, Glucagonoma and Insulinoma, sponsored by National Cancer Institute (NCI). Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-11-17.

Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 93
Allocation: Non-randomized
Ages: 18 Years and older
Sex: All

Study summary

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.

Read the 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.

Conditions studied

Gastrinoma
Glucagonoma
Insulinoma
Metastatic Gastrointestinal Carcinoid Tumor
Neuroendocrine Tumor
Pancreatic Polypeptide Tumor
Recurrent Gastrointestinal Carcinoid Tumor
Recurrent Islet Cell Carcinoma
Somatostatinoma
WDHA Syndrome

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In context

Gastrinoma

28 studies on the registry are indexed under Gastrinoma; none are open to participants now.

This study's enrollment of 93 is above the median of 39 across 20 interventional studies indexed under Gastrinoma.

Browse Gastrinoma studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,554 studies on the registry; 334 are open to participants now.

Of its 407 completed or terminated interventional studies of FDA-regulated products, 370 (91%) have results posted.

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Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility 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

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 93 participants (actual)

Study arms

Experimental
Group A (patients with carcinoid tumors)
Patients receive 400 mg oral sorafenib twice daily on days 1-28.
Drug: sorafenib tosylate
Experimental
Group B (islet cell and other neuroendocrine tumors)
Patients receive 400 mg oral sorafenib twice daily on days 1-28.
Drug: sorafenib tosylate

Interventions

Drugsorafenib tosylate
400 mg given orally
Also known as: BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, Nexavar, SFN

What researchers measure

Primary outcomes

Confirmed Response Rate
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.
Time frame: Duration of Treatment (Up to 2 years)

Secondary outcomes

Toxicity
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.
Time frame: Up to 2 years
Overall Survival
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.
Time frame: From registration to death (up to 2 years)
Progression Free Survival
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.
Time frame: Time from registration to progression or death (up to 2 years)
Duration of Response
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.
Time frame: Time from response to progression (up to 2 years)

Results

Posted Nov 17, 2014

Participant flow

Between June 21, 2005 and September 15, 2006, a total of 93 (51 carcinoid, 42 islet cell) patients initiated treatment on this study.

Participant flow — Overall Study
Milestone	Group A (Patients With Carcinoid Tumors)	Group B (Islet Cell and Other Neuroendocrine Tumors)
Started	51	42
Completed	50	42
Not completed	1	0
Withdrew: Withdrawal by subject	1	0

Outcome measures

PrimaryConfirmed Response Rate

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.

Time frame:: Duration of Treatment (Up to 2 years)
Reported as:: Number · percentage of participants

Confirmed Response Rate
percentage of participants	Group A (Patients With Carcinoid Tumors)	Group B (Islet Cell and Other Neuroendocrine Tumors)
Confirmed Response Rate	10 (3 to 24)	14 (6 to 32)

SecondaryToxicity

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.

Time frame:: Up to 2 years
Reported as:: Number · participants

Toxicity
participants	Group A (Patients With Carcinoid Tumors)	Group B (Islet Cell and Other Neuroendocrine Tumors)
Grade 3 Toxicity	37	25
Grade 4 or Grade 5 Toxicity	5	2

SecondaryOverall Survival

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.

Time frame:: From registration to death (up to 2 years)
Reported as:: Median · months

Overall Survival
months	Group A (Patients With Carcinoid Tumors)	Group B (Islet Cell and Other Neuroendocrine Tumors)
Overall Survival	25.6 (15.5 to 30.2)	NA (NA to NA)

SecondaryProgression Free Survival

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.

Time frame:: Time from registration to progression or death (up to 2 years)
Reported as:: Median · months

Progression Free Survival
months	Group A (Patients With Carcinoid Tumors)	Group B (Islet Cell and Other Neuroendocrine Tumors)
Progression Free Survival	9.1 (5.7 to 12.7)	12.7 (8.3 to 19.9)

SecondaryDuration of Response

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.

Time frame:: Time from response to progression (up to 2 years)
Reported as:: Median · months

Duration of Response
months	Group A (Patients With Carcinoid Tumors)	Group B (Islet Cell and Other Neuroendocrine Tumors)
Duration of Response	6.7 (3.7 to 9.2)	9.2 (3.7 to 32)

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
All Patients	—	52/93 (55.9%)	90/93 (96.8%)

Most frequent serious events

Showing 10 of 84

Most frequent serious events
Event	All Patients
Abdominal painGastrointestinal disorders	18/93
FatigueGeneral disorders	15/93
NauseaGastrointestinal disorders	13/93
AnorexiaMetabolism and nutrition disorders	10/93
VomitingGastrointestinal disorders	8/93
DehydrationMetabolism and nutrition disorders	6/93
MyalgiaMusculoskeletal and connective tissue disorders	6/93
DyspneaRespiratory, thoracic and mediastinal disorders	6/93
DiarrheaGastrointestinal disorders	5/93
Ear, nose and throat examination abnormalGastrointestinal disorders	4/93

Most frequent other events

Showing 10 of 131

Most frequent other events
Event	All Patients
DiarrheaGastrointestinal disorders	65/93
FatigueGeneral disorders	63/93
Hand-and-foot syndromeSkin and subcutaneous tissue disorders	52/93
Rash acneiformSkin and subcutaneous tissue disorders	51/93
HypertensionVascular disorders	51/93
AlopeciaSkin and subcutaneous tissue disorders	46/93
NauseaGastrointestinal disorders	45/93
AnorexiaMetabolism and nutrition disorders	39/93
Ear, nose and throat examination abnormalGastrointestinal disorders	35/93
Abdominal painGastrointestinal disorders	34/93

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Group A (Patients With Carcinoid Tumors)	Group B (Islet Cell and Other Neuroendocrine Tumors)	Total
Median	60 (38 to 82)	56.5 (26 to 78)	59 (26 to 82)

Sex: Female, Male
Sex: Female, Male(Participants)	Group A (Patients With Carcinoid Tumors)	Group B (Islet Cell and Other Neuroendocrine Tumors)	Total
Female	28	21	49
Male	23	21	44

Region of Enrollment
Region of Enrollment(participants)	Group A (Patients With Carcinoid Tumors)	Group B (Islet Cell and Other Neuroendocrine Tumors)	Total
United States	51	42	93

Study locations

1 site

Mayo Clinic
Rochester, Minnesota 55905, United States

Timeline

Tracking since Sep 25, 2026

Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of Jun 2005, a primary completion of Oct 2010 and a completion of Apr 2013. It does not say whether these dates are actual or estimated.

Results were first posted in Nov 2014, 4 years 1 month after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered: Aug 16, 2005
First posted: Aug 19, 2005
Start: Jun 2005
Primary completionActual: Oct 2010
CompletionActual: Apr 2013
Results first posted: Nov 17, 2014
Last update: Nov 17, 2014

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on Nov 17, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00131911
Lead sponsor: National Cancer Institute (NCI)
Responsible party: Sponsor
First posted: Aug 19, 2005
Start date: Jun 2005
Primary completion: Oct 2010
Completion: Apr 2013
Results posted: Nov 17, 2014
Last update: Nov 17, 2014

Study contacts

Timothy Hobday

principal investigator · Mayo Clinic

View the source record on ClinicalTrials.gov ↗

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