Evaluating the efficacy and safety of sunitinib in patients with progressive, advanced/metastatic well-differentiated, unresectable pancreatic neuroendocrine tumors.
ID
Source
Brief title
Condition
- Neoplastic and ectopic endocrinopathies
- Endocrine neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Progression Free Survival (PFS)
Secondary outcome
Objective Response Rate (ORR)
Overall Survival (OS)
Background summary
The purpose of this study is to evaluate the efficacy and safety of sunitinib
in patients with progressive, advanced/metastatic well-differentiated,
unresectable pancreatic neuroendocrine tumors. Pancreatic neuroendocrine tumors
(NET) are rare malignancies and because of the relatively indolent nature of
this disease, the majority of patients are diagnosed with disseminated
metastases. The resistance to traditional treatment modalities distinguishes
well differentiated neuroendocrine tumors from poorly differentiated carcinoma
and small cell carcinoma.
With the exception of surgery for localized disease, there was a lack of
available therapies with meaningful, clinical benefit for well differentiated
pancreatic NET until recently. Available treatment options for unresectable
disease have included the use of somatostatin analogs, which may relieve
symptoms related to hormonal hypersecretion, but there is little evidence to
support a direct antitumor effect.
Since 2010, Sunitinib (Sutent®) is registered in the Netherlands for the
treatment of progressive, advanced/metastatic well-differentiated, unresectable
pancreatic neuroendocrine tumors. This indicates that the Dutch government has
the opinion that prescribing sunitinib for this indication is well-considered.
However, experience with sunitinib as first line treatment is still limited.
This research will be done to collect more data on the efficacy and safety of
the drug as a first line treatment of this type of pancreatic cancer in an
advanced stage. This study is conducted to meet regulatory post-marketing
commitments of the FDA.
Study objective
Evaluating the efficacy and safety of sunitinib in patients with progressive,
advanced/metastatic well-differentiated, unresectable pancreatic neuroendocrine
tumors.
Study design
The patient participates in the study approximately 1 year on average; in this
period the patient will visit the hospital every 2 weeks (first month) or 4
weeks (after first month), 16 visits in total. During these visits the
following procedures will be performed:
* Discuss medical history, treatments, and drug use complaints.
* Measurement of blood pressure, pulse, temperature and weight and any further
physical examination.
* Blood tests (about 20 ml each time) to examine:
- Overall health status (including thyroid) assessment.
- The amount of sunitinib in the blood.
- the pancreas, the severity of the disease and the
possible impact of the study treatment thereon.
* Urinalysis to assess the general health status.
* Pregnancy test (if applicable).
* Assessment of the tumor with a CT scan and possibly a bone scan.
* ECG ("ECG").
* Measurement of the pumping power of the heart with an echocardiogram or MUGA
scan
* Completion of two questionnaires on health and daily activities. .
Four weeks after treatment, there is a final visit. After treatment with study
medication, the patient in the follow-up phase will be called every 8 weeks, up
to 5 years once all patients are included.
Intervention
- oral intake of 37.5 mg study medication once a day on a continuous daily
dosing regimen (CDD)
- laboratory assessments (blood and urine)
- questionnaires
Study burden and risks
All medicines have side effects, as well sunitinib. Side effects often
disappear when the drug is stopped. They can also remain for a longer period or
permanently. Side effects can be mild, but also severe and even life
threatening. However, there may be not previously reported, potentially
serious, side effects. Furthermore, the patient may also experience an allergic
reaction to the drug.
40% or more of patients experienced: diarrhea, fatigue, nausea.
10-40% of patients experienced: vomiting, blisters and/or rash on hands and
feet that may be painful, decreases in red blood cells (oxygen carrying cells),
decreases in platelets (which help stop and prevent you from bleeding), high
blood pressure, inflammation of mucous membranes (including mouth sores), taste
disturbances, constipation, decreases in white blood cells (infection-fighting
cells), upset stomach, decreased appetite (including anorexia), abdominal pain,
shortness of breath, headache, rash, cough, fever, back pain, swelling, pain
in extremities (hand and feet), skin, hair, and nail color changes, nosebleed,
joint pain, decreased thyroid function, dry skin, inability to sleep.
5-10% of patients experienced: weight loss, dizziness, muscle aches, chest
pain, hair loss, dehydration, dry mouth, skin redness, bloating, flatulence,
throat pain, heartburn and indigestion, itching, burning sensation of the
tongue, chills, swelling in the face, infection, watering of the eye, increased
levels of liver enzymes, skin peeling, depression.
RISK OF PROCEDURES
A blood draw may cause faintness, inflammation of the vein, pain, bruising, or
bleeding at the site of puncture
In a CT or bone scan, the patient is subject to additional radiation. In this
study there are no more scans performed than during treatment of the disease
outside a research setting. The patient is not exposed to more radiation
because of study participation. The injection of contrast may hurt.
Occasionally patients experience a hypersensitivity reaction.
In a MUGA scan, radioactive material is injected. The amount of radiation is
less than 2 times the amount to which we are exposed in everyday life in one
year . Cardiac function may also be assessed by an echocardiogram. In that
case, no radioactivity is used.
Rivium Westlaan 142
2909 LD Capelle a/d IJssel
NL
Rivium Westlaan 142
2909 LD Capelle a/d IJssel
NL
Listed location countries
Age
Inclusion criteria
1. Histologically or cytologically proven diagnosis of well differentiated pancreatic neuroendocrine tumor (according to WHO 2000 classification) with available Ki-67 index.;2. Unresectable (as assessed by the investigator) or metastatic disease documented on a scan (CT, MRI, or Octreoscan) taken within 28 days of study enrollment. Disease progression (per RECIST 1.0) within 12 months prior to study enrollment. ;3. Disease that is not amenable to surgery, radiation, or combined modality therapy with curative intent.;4. Presence of at least one measurable target lesion for further evaluation according to RECIST 1.0 (contrast enhancing lesion with the largest diameter larger or equal to 20 mm, based on conventional CT scan (or larger or equal to 10 mm with spiral CT scan) done within 3 weeks before the start of treatment).
Exclusion criteria
1. Patients with poorly-differentiated pancreatic neuroendocrine tumors (according to WHO 2000 classification). ;2. Prior treatment with any tyrosine kinase inhibitors, anti-VEGF angiogenesis inhibitors, non-VEGF-targeted angiogenesis inhibitors, or mTOR inhibitors.;3. Diagnosis of any second malignancy within the last 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ carcinoma of the cervix uteri.;4. Treatment with strong CYP3A4 inhibitors and inducers within 7 and 12 days, respectively, prior to study drug administration.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-004363-74-NL |
| ClinicalTrials.gov | NCT01525550 |
| CCMO | NL39081.042.12 |