Efficacy of Medical Treatment With SOM230 LAR in Patients With Primary Inoperable Thymoma and/or With Local Recurrent Thymoma to Reduce Tumor Size

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.

Study Overview

• Status: Completed
• Conditions: Primary Inoperable Thymoma; Local Recurrent Thymoma
• Intervention / Treatment: Drug: SOM230 LAR

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Bavaria
    • Regensburg, Bavaria, Germany, 93053
      • Klinik und Poliklinik für Neurologie der Universität Regensburg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SOM230 LAR; SOM230 LAR in a dosage of 60 mg i.m. once every 4 weeks	Drug: SOM230 LAR; SOM230 LAR in a dosage of 60 mg is administered i.m. once every 4 weeks.; Other Names: Pasireotide; Sandostatin®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Tumor Volume From Baseline to EOS	To evaluate whether SOM230 LAR is effective in patients with inoperable thymoma with respect to shrinkage of tumor volume. Response is defined as the decrease in tumor volume of 20 % at EOS as compared to baseline. Tumor shrinkage is assessed by CT or MRI.	at least 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor Resection Status	To evaluate the resection status based on the categories R0, R1 and ≥ R2 at EOS using CT or MRI imaging. R0 resection means no residual tumor tissue (best status); R1 indicates microscopic residual tumor tissue and R2 indicates macroscopic residual tumor tissue (worst status).	at least 6 months
Assessment of Tumor Operability	Assessment if patients reaching operability at the EOS.	at least 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)		at least 6 months
Assessment of Myasthenia Gravis (MG) Status by Determining Titin-antibody Status	MG severity status is assessed by determining Titin-antibody status at Baseline and EOS.	at least 6 months
Assessment of Myasthenia Gravis (MG) Status by Measuring ACHR-antibody Concentrations	MG severity status is assessed by measuring ACHR-antibody concentrations at Baseline and EOS.	at least 6 months
Health Related Quality of Life	Health related quality of life information was collected at Baseline and EOS using SF-36 questionnaire. Questionnaires had to be completed by the patients. All questions are scored on a scale from 0 to 100, with 100 representing the highest level of functioning possible. Patient reported answers were transformed into domain scores according to the guidelines provided by RAND/MOS. Statistical significance of the result was tested with a paired Wilcoxon rang sum test with a significance level of 0.05 considering only paired values (n=11) using PSPP Version 0.10.1.	at least 6 months

Collaborators and Investigators

• Sponsor: Prof. Dr. Berthold Schalke
• Collaborators: Crolll Gmbh
• Investigators: Principal Investigator: Berthold Schalke, Prof. Dr., Professor

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: December 20, 2013
• First Submitted That Met QC Criteria: December 20, 2013
• First Posted (Estimate): December 27, 2013

Study Record Updates

• Last Update Posted (Actual): February 5, 2018
• Last Update Submitted That Met QC Criteria: July 19, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: primary inoperable thymoma; local recurrent thymoma; reduction of tumor size; SOM230 LAR
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Lymphatic Diseases; Neoplasms by Site; Disease Attributes; Thoracic Neoplasms; Neoplasms, Complex and Mixed; Recurrence; Thymoma; Thymus Neoplasms; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pasireotide
• Other Study ID Numbers: CSOM230CIC01T