Estudio multicéntrico, aleatorizado, ciego, de eficacia y seguridad de pasireotida LAR frente a octreotida LAR, en pacientes con tumores carcinoides metastásicos cuyos síntomas relacionados con la enfermedad no están suficientemente controlados con análogos de la somatostatina

Conditions: tumores carcinoides avanzados
MedDRA version: 9.1Level: LLTClassification code 10007271Term: Carcinoid tumor

Registration Number: EUCTR2007-000739-25-ES

Lead Sponsor: ovartis Farmaceutica, S.A

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 202

Inclusion Criteria

? Male or female patients aged 18 years or greater.
? Patients with histopathologically confirmed (from primary or metastatic lesion biopsy) metastatic carcinoid tumors of the digestive system with extent of disease determined by Computer Tomography (CT) scan or Magnetic Resonance Imaging (MRI).
? Symptoms of carcinoid disease, diarrhea and flushing, must be inadequately controlled:
Inadequate control: a daily mean of 4 or more bowel movements over a two week period and a total of 5 or more flushing episodes during this period, while receiving the highest recommended dose of one of the following somatostatin analogues:
? octreotide LAR (= 30 mg q 28 days)
? octreotide s.c. (= 600 ?g total daily dose)
? lanreotide Autogel (= 120 mg q 28 days)
? lanreotide SR (= 30 mg q 14 days)
? Patients with measurable or evaluable disease per RECIST criteria (see Post-text
supplement 1)
? Karnofsky Performance Status ? 60 (Requires occasional assistance, but is able to care for most of his personal needs, or better)
? Patients must complete the following washout periods before randomization:
? octreotide LAR, lanreotide autogel or any other long-acting somatostatin analogues: 8 weeks
? lanreotide SR: 4 weeks
? prescription oral opioids: 5 days
? octreotide s.c., other short-acting somatostatin analogues or any other antidiarrheals: 48 hours
Note that during the washout period for long-acting somatostatin analogues, octreotide s.c. or any other short-acting antidiarrheal agents may be administered after the baseline symptoms have been collected. However these are not to be taken during the last 48 hours of the washout period prior to randomization.
? Patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary (see Section 6.6.2.1)
? Female patients of child bearing potential must have a negative pregnancy test at baseline.
? Patients for whom written informed consent to participate in the study has been obtained
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

?Patients receiving radiolabeled somatostatin analogue therapy within the 6 months or any
cytotoxic chemotherapy or interferon therapy within the 2 months prior to recording
baseline symptoms
? Patients who have undergone major surgery/surgical therapy for any cause within 1 month
or surgical therapy of loco-regional metastases within the last 3 months before recording
baseline symptoms
? Patients with hepatic artery embolization within the last 6 months (1 month if there are
other sites of measurable disease), or patients who have undergone cryoablation or
radiofrequency ablation of hepatic metastasis within the last 2 months before recording
baseline symptoms
? Patients who have received radiotherapy for any reason within the last 4 weeks must have
recovered from any side effects of radiotherapy before recording baseline symptoms
? Patients who are unwilling to follow dietary restrictions (see Section 7.4.2.7) within 3
days of urinary 5-HIAA sample collection or require medications that would interfere with
urinary 5-HIAA measurement (e.g. Reserpine, mephenesin carbamate, Lugol?s solution)
? Patients with malabsorption syndrome, short bowel or chologenic diarrhea not controlled
by specific therapeutic means
? Patients who are not biochemically euthyroid
? Diabetic patients on antidiabetic medications whose fasting blood glucose is poorly
controlled as indicated by HbA1C > 8%
? Patients with symptomatic cholelithiasis
? Patients who have congestive heart failure (NYHA Class III or IV), unstable angina,
sustained ventricular tachycardia, ventricular fibrillation, clinically significant
bradycardia, advanced heart block or a history of acute myocardial infarction within the
six months preceding enrollment
? Patients with risk factors for torsades de pointes, i.e. patients with a baseline QTc > 450
ms, hypokalemia, hypomagnesemia, hypocalcemia, family history of long QT syndrome,
and concomitant medications known to prolong the QT interval
? Patients with liver disease such as cirrhosis, chronic active hepatitis or chronic persistent
hepatitis with serum creatinine > 2.0 X ULN, serum bilirubin > 2 X ULN, serum albumin
< 0.67 X LLN, and/or ALT or AST more than 2 X ULN for patients without liver
metastases or ALT or AST more than 5X ULN for patients with documented liver
metastases
? Patients with additional active malignant disease within the last five years (with the
exception of basal cell carcinoma or carcinoma in situ of the cervix)
? Patients with the presence of active or suspected acute or chronic uncontrolled infection or
with a history of immunocompromise, including a positive HIV test result (ELISA and
Western blot). A HIV test will not be required; however, previous medical history will be
reviewed
? Patients with abnormal coagulation (PT or APTT elevated by 30% above normal limits) or
patients receiving anticoagulants that affect PT (prothrombin time) or APTT ( activated
thromboplastin time)
? Patients with WBC <2.5 X 109/L; Hgb <10 g/dL; PLT <100 X 109/L
? Patients who have any current or prior medical condition that may interfere with the
conduct of the study or the evaluation of its results in the opinion of the Investigator or the
Sponsor?s Medical Monitor
? Female patients who are pregnant or lactating, or are of childbearing potential and not
practicing a medically acceptable method of birth control. Female patients must use
barrier contraception with condoms. If oral contraception is used in addition to condoms,
the pat