Efficacy of Medical Treatment With SOM230 LAR in Patients With Primary Inoperable Thymoma and/or With Local Recurrent Thymoma to Reduce Tumor Size
Condition: Primary Inoperable Thymoma; Local Recurrent Thymoma
MeSH terms: Thymoma; Thymus Neoplasms; Recurrence
Intervention: SOM230 LAR
Intervention description: SOM230 LAR in a dosage of 60 mg is administered i.m. once every 4 weeks.
Intervention MeSH terms: Pasireotide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: primary inoperable thymoma; local recurrent thymoma; reduction of tumor size; SOM230 LAR

Summary:

      This is a monocenter, single-arm, open label phase II trial evaluating the effect of SOM230
      LAR in adult patients with inoperable primary thymoma and thymoma metastasis (Masaoka
      II-IVa). SOM230 LAR in a dosage of 60 mg is administered i.m. once every 4 weeks. The purpose
      of this trial is a proof of concept.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female patients aged ≥18 years

          -  Diagnosis of thymoma as assessed by biopsy and/or szintigraphy

          -  Inoperability of thymoma or loco-regional metastases. Inoperability is defined as at
             least adherence of the tumor to the neighbored organs, suspicious to infiltrate
             neighbored organs or local metastasis so that R0 resection can not be expected and /or
             local recurrence of thymic tumor

          -  Tumor stage: Thymomas of all WHO based histological subtypes (WHO A, AB, B1, B2, B3)
             (Rosai, 1999; Travis 2004) at Masaoka stage II to IVa based on histological
             examination of resection specimens or core biopsies.

          -  Patients with and without thymoma associated paraneoplastic syndrome.

          -  Performance status 0,1, or 2 (ECOG)

          -  Patients for whom written informed consent to participate in the study has been
             obtained

        Exclusion Criteria:

          -  Patients having received 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 who have received radiotherapy for any reason within the last 4 weeks and
             must have recovered from any side effects of radiotherapy before recording baseline
             symptoms

          -  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 QT related risk factor: QTcF at screening > 450 msec

          -  Patients with QT related risk factor: History of syncope or family history of
             idiopathic sudden death

          -  Patients with QT related risk factor:Sudden or clinically significant cardiac
             arrhythmias

          -  Patients with QT related risk factor: Risk factors for Torsades de Pointes such as
             hypokalemia, hypomagnesemia, cardiac failure, clinically significant / symptomatic
             bradycardia, or high-grade AV block

          -  Patients with QT related risk factor: Concomitant disease(s) that could prolong QT
             such as autonomic neuropathy (caused by diabetes or Parkinson's disease), HIV,
             cirrhosis, uncontrolled hypothyroidism or cardiac failure

          -  Patients with QT related risk factor: Concomitant medication(s) known to increase the
             QT interval

          -  Patients with potassium <3.0 mmol/L at study entry, magnesium <0.4 mmol/L at study
             entry, calcium <1.75 mmol/L at study entry, family history of long QT syndrome, and
             concomitant medications known to prolong the QT interval. If the electrolyte
             abnormalities are corrected prior to study commencement, the patient may become
             eligible for the trial.

          -  Patients with liver disease such as cirrhosis, chronic active hepatitis or chronic
             persistent hepatitis with serum bilirubin > 1.5 X ULN, serum albumin < 0.67 X LLN,
             and/or ALT or AST more than 2 X ULN for patients without liver Confidential - 20 -
             Amended Clinical Study Protocol v01 / Track Changes Study No. CSOM230CIC01T 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)

          -  Patients with WBC <2.5 X 109/L; Hgb <10 g/dL; PLT <100 X 109/L (patients with
             paraneoplastic pan-, leuco-, erythro- or thrombopenia can be included if this seems to
             be the only reason for pan-, leuco-, erythro- or thrombopenia)

          -  Known hypersensitivity to somatostatin analogues or any component of the pasireotide
             or octreotide LAR or s.c. formulations

          -  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

          -  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 a secure method of contraception if sexually active and the partner should use a
             condom. If oral contraception is used, the patient must have been practicing this
             method for at least two months prior to enrollment and must agree to continue the oral
             contraceptive throughout the course of the study, and for three months after the study
             has ended. Male patients who are sexually active are required to use condoms during
             the study and for three months afterwards as a precautionary measure (available data
             do not suggest any increased reproductive risk with the study drugs). Female partners
             of these male patients should use a secondary barrier contraception.

          -  Patients who are currently part of or have participated in any clinical investigation
             with an investigational drug within 1 month prior to dosing

          -  Patients with a history of non-compliance to medical regimens or who are considered
             potentially unreliable or will not be able to complete the entire study

          -  Patient has received any other investigational agents within 28 days of first day of
             study drug dosing

          -  Abnormal clinical laboratory values considered by the investigator to be clinically
             significant and which could affect the interpretation of the study results