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A Phase II, Open Label, Uncontrolled and Multicenter Trial of Pazopanib Given as a Single Agent in Patients With Progressive Advanced/Metastatic Neuroendocrine Tumors (NET): a Search for Activity, Safety, and Predictive Biomarkers


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Advanced/Metastatic Neuroendocrine Tumors

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Trial Information

A Phase II, Open Label, Uncontrolled and Multicenter Trial of Pazopanib Given as a Single Agent in Patients With Progressive Advanced/Metastatic Neuroendocrine Tumors (NET): a Search for Activity, Safety, and Predictive Biomarkers


Inclusion Criteria:



1. Subjects must provide signed informed consent form prior to performance of
study-specific procedures or assessments, and must be willing to comply with
treatment and follow‑up.

Procedures conducted as part of the subject's clinical routine (e.g., blood count,
imaging study) and obtained prior to signing the consent form might be used for
screening or baseline purposes provided these procedures have been conducted as
specified in the protocol.

2. Age ≥ 18 years.

3. Diagnosis of pancreatic islet cell tumors, well differentiated gastrointestinal NETs,
pulmonary carcinoids and well differentiated thymic carcinoids. Locally-advanced or
metastatic disease documented as progressive by CT scan, MRI, or Octreoscan at
baseline and within 12 months prior to baseline. The previous scans will be used to
classify the patient as having progressive disease at baseline according to RECIST
criteria. Octreoscan results may be used to document progressive disease at baseline,
but not for RECIST determination during the study.

4. ECOG performance status 0-1.

5. Disease not amenable to surgery, radiation or combined modality therapy with curative
intent.

6. Presence of at least one dimensionally measurable target lesion for further
evaluation according to RECIST 1.0 criteria (contrast enhancing lesion with the
largest diameter > 1cm, based on CT or MRI scan done within 4 weeks before the start
of treatment).

7. Patients could have received treatment with somatostatin analogs, chemotherapy,
anti-VEGF, and anti-mTOR agents previously to the entrance into this study if the
final toxicity was grade ≤ 1.

8. From patients who sign an informed consent form to donate biological samples: Tumor
tissue must be provided for all available subjects at baseline and serum samples will
be collected at baseline and at week 12 of treatment for biomarker analysis as
defined at the biomarker section of this protocol.

9. Adequate organ system function as follows:

9.1.Hematologic system:

- Absolute neutrophil count (ANC) ≥ 1.5 X 10^9/L

- Hemoglobin (1) ≥ 9 g/dL (5.6 mmol/L)

- Platelets ≥ 100 X 10^9/L

- Prothrombin time (PT) or international normalized ratio (INR) ≤ 1.2 X upper
limit of normal (ULN)

- Partial thromboplastin time (PTT) ≤ 1.2 X ULN

9.2.Hepatic system (2):

- Total bilirubin ≤ 1.5 X ULN

- AST and ALT ≤ 2.5 X ULN

9.3.Renal system:

- Serum creatinine ≤ 1.5 mg/dL (133 µmol/L),

Or, if greater than 1.5 mg/dL:

- Calculated creatinine clearance ≥ 50 mL/min

(Note 1):"Subjects should not have had a transfusion within 7 days of screening
assessment." (Note 2): "Concomitant elevations in bilirubin and AST/ALT above 1.0 x
ULN are not permitted"

10. A female is eligible to enter and participate in this study if she is of:

10.1.Non-childbearing potential (i.e., physiologically incapable of becoming
pregnant), including any female who has had:

- A hysterectomy

- A bilateral oophorectomy (ovariectomy)

- A bilateral tubal ligation

- Is post-menopausal

10.2.Childbearing potential, including any female who has had a negative serum
pregnancy test within 2 weeks prior to the first dose of study treatment, preferably
as close to the first dose as possible, and agrees to use adequate contraception.
GETNE acceptable contraceptive methods, when used consistently and in accordance with
both the product label and the instructions of the physician, are as follow:

- An intrauterine device with a documented failure rate of less than 1% per year.

- Vasectomized partner who is sterile prior to the female subject's entry and is
the sole sexual partner for that female.

- Complete abstinence from sexual intercourse for 14 days before exposure to
investigational product, through the dosing period, and for at least 21 days
after the last dose of investigational product.

- Double-barrier contraception (condom with spermicidal jelly, foam suppository,
or film; diaphragm with spermicide; or male condom and diaphragm with
spermicide).

- Oral contraceptives

- Female subjects who are lactating should discontinue nursing prior to the first
dose of study drug and should refrain from nursing throughout the treatment
period and for 14 days following the last dose of study drug.

11. Life expectancy > 3 months.

12. Able to swallow oral compound.

13. Signed and dated informed consent document indicating that the patient has been
informed of all pertinent aspects of the trial prior to enrollment.

14. Willingness and ability to comply with scheduled visits, treatment plans, laboratory
tests and other study procedures.

Exclusion Criteria:

1. 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.

2. History or clinical evidence of central nervous system (CNS) metastases or
leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS
metastases, are asymptomatic, and have had no requirement for steroids or
anti-seizure medication for 6 months prior to first dose of study drug. Screening
with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging
[MRI]) is required only if clinically indicated or if the subject has a history of
CNS metastases.

3. Clinically significant gastrointestinal abnormalities that may increase the risk for
gastrointestinal bleeding including, but not limited to:

3.1.Active peptic ulcer disease 3.2.Known intraluminal metastatic lesion/s with risk
of bleeding 3.3.Inflammatory bowel disease (e.g. ulcerative colitis, Chrohn's
disease), or other gastrointestinal conditions with increased risk of perforation
3.4.History of abdominal fistula, gastrointestinal perforation, or intra‑abdominal
abscess within 28 days prior to beginning study treatment.

4. Clinically significant gastrointestinal abnormalities that may affect absorption of
investigational product including, but not limited to:

4.1.Malabsorption syndrome 4.2.Major resection of the stomach or small bowel.
4.3.Active peptic ulcer disease 4.4.Known intraluminal metastatic lesion/s with risk
of bleeding 4.5.Inflammatory bowel disease (e.g. ulcerative colitis, Chrohn's
disease), or other gastrointestinal conditions with increased risk of perforation
4.6.History of abdominal fistula, gastrointestinal perforation, or intra‑abdominal
abscess within 28 days prior to beginning study treatment.

5. Presence of uncontrolled infection.

6. Corrected QT interval (QTc) > 480 msecs using Bazett's formula.

7. History of any one or more of the following cardiovascular conditions within the past
6 months:

7.1.Cardiac angioplasty or stenting 7.2.Myocardial infarction 7.3.Unstable angina
7.4.Coronary artery bypass graft surgery 7.5.Symptomatic peripheral vascular disease
7.6.Class III or IV congestive heart failure, as defined by the New York Heart
Association (NYHA)

8. Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140 mmHg
or diastolic blood pressure (DBP) of ≥ 90mmHg].

9. History of cerebrovascular accident including transient ischemic attack (TIA),
pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6
months.

Note: Subjects with recent DVT who have been treated with therapeutic
anti-coagulating agents for at least 6 weeks are eligible.

10. Prior major surgery or trauma within 28 days prior to first dose of study drug and/or
presence of any non-healing wound, fracture, or ulcer (procedures such as catheter
placement not considered to be major).

11. Evidence of active bleeding or bleeding diathesis.

12. Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels.

13. Hemoptysis in excess of 2.5ml within 8 weeks of first dose of study drug.

14. Any serious and/or unstable pre-existing medical, psychiatric, or other condition
that could interfere with subject's safety, provision of informed consent, or
compliance to study procedures.

15. Unable or unwilling to discontinue use of prohibited medications list in Concomitant
Medication Section for at least 14 days or five half-lives of a drug (whichever is
longer) prior to the first dose of study drug and for the duration of the study.

16. Treatment with any of the following anti-cancer therapies:

- radiation therapy, surgery or tumor embolization within 28 days prior to the
first dose of pazopanib, or

- chemotherapy, immunotherapy, biological therapy, investigational therapy or
hormonal therapy within 28 days prior to the first dose of pazopanib.

17. Any ongoing toxicity from prior anti-cancer therapy that is > Grade 1 and/or that is
progressing in severity, except alopecia.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Clinical Benefit Rate at six months

Outcome Description:

Defined as the percentage of patients with a confirmed CR or PR and SD as per RECIST 1.0 criteria at six months.

Outcome Time Frame:

anticipated 3 years

Safety Issue:

No

Principal Investigator

Enrique Grande Pulido, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Grupo Espanol de Tumores Neuroendocrinos

Authority:

Spain: Agencia Española de Medicamentos y Productos Sanitarios

Study ID:

GETNE-1002

NCT ID:

NCT01280201

Start Date:

December 2010

Completion Date:

December 2013

Related Keywords:

  • Advanced/Metastatic Neuroendocrine Tumors
  • Neuroendocrine Tumors
  • Pazopanib
  • GETNE
  • Biomarkers
  • Neuroendocrine Tumors

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