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

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ClinicalTrials.gov Identifier: NCT02021942

Recruitment Status : Completed

First Posted : December 27, 2013

Results First Posted : February 5, 2018

Last Update Posted : February 5, 2018

Sponsor:

Collaborator:

Crolll Gmbh

Information provided by (Responsible Party):

Prof. Dr. Berthold Schalke, University of Regensburg

Study Type	Interventional
Study Design	Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Conditions	Primary Inoperable Thymoma Local Recurrent Thymoma
Intervention	Drug: SOM230 LAR
Enrollment	16

Participant Flow

Recruitment Details	This monocentric trial was conducted in Regensburg, Germany. The patients were asked for study participation by the investigator.
Pre-assignment Details


Arm/Group Title	SOM230 LAR
Arm/Group Description	SOM230 LAR in a dosage of 60 mg i.m...
Arm/Group Description	SOM230 LAR in a dosage of 60 mg i.m. once every 4 weeks
Period Title: Overall Study
Started	16
Completed	16
Not Completed	0

Baseline Characteristics

Arm/Group Title		SOM230 LAR
Arm/Group Description		SOM230 LAR in a dosage of 60 mg i.m...
Arm/Group Description		SOM230 LAR in a dosage of 60 mg i.m. once every 4 weeks
Overall Number of Baseline Participants		16
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	16 participants
		52.6 (12.7)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	16 participants
	Female	7 43.8%
	Male	9 56.3%
Region of Enrollment Measure Type: Count of Participants Unit of measure: Participants
Germany	Number Analyzed	16 participants
Germany		16 100.0%

Outcome Measures

1.Primary Outcome


Title	Percent Change in Tumor Volume From Baseline to EOS
Description	To evaluate whether SOM230 LAR is effective in patients with inoperabl...
Description	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.
Time Frame	at least 6 months

Outcome Measure Data

Analysis Population Description

Initial diagnosis of thymoma for one patient could not be confirmed, but a squamous cell carcinoma was diagnosed by the central pathologist. Tumor voume was 320.99 cm^3 at screening. Tumor size was reduced to 176.87 cm^3 at month 2 (-44.9 % compared to baseline). At month 4 (EOS) tumor volume was slightly increased compared to month 2 (189 cm^3).


Arm/Group Title	SOM230 LAR
Arm/Group Description:	SOM230 LAR in a dosage of 60 mg i.m...
Arm/Group Description:	SOM230 LAR in a dosage of 60 mg i.m. once every 4 weeks
Overall Number of Participants Analyzed	16
Mean (95% Confidence Interval) Unit of Measure: percentage of tumor volume
	-37.38 (-60.88 to -13.88)

2.Secondary Outcome


Title	Tumor Resection Status
Description	To evaluate the resectio...
Description	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).
Time Frame	at least 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	SOM230 LAR
Arm/Group Description:	SOM230 LAR in a dosage of 60 mg i.m...
Arm/Group Description:	SOM230 LAR in a dosage of 60 mg i.m. once every 4 weeks
Overall Number of Participants Analyzed	16
Measure Type: Count of Participants Unit of Measure: Participants
Surgery performed with resection status R0	6 37.5%
Surgery performed with resection status R1	4 25.0%
No surgery performed	6 37.5%

3.Secondary Outcome


Title	Assessment of Tumor Operability
Description	Assessment if patients reaching operability at the EOS.
Description	Assessment if patients reaching operability at the EOS.
Time Frame	at least 6 months

Outcome Measure Data

Analysis Population Description

Operability of the tumor at the EOS was based on the decision of the treating surgeon. In addition the response criteria had to be fulfilled.

The tumors of 11 patients (68.75%) were operable. One of these patients decided not to undergo surgery. Tumors of 5 patients were inoperable (31.25%) at the EOS.


Arm/Group Title	SOM230 LAR
Arm/Group Description:	SOM230 LAR in a dosage of 60 mg i.m...
Arm/Group Description:	SOM230 LAR in a dosage of 60 mg i.m. once every 4 weeks
Overall Number of Participants Analyzed	16
Measure Type: Count of Participants Unit of Measure: Participants
Tumor assesed as operable.	11 68.8%
Tumor assesed as not operable.	5 31.3%

4.Other Pre-specified Outcome


Title	Safety: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
Description	[Not Specified]
Description	[Not Specified]
Time Frame	at least 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	SOM230 LAR
Arm/Group Description:	SOM230 LAR in a dosage of 60 mg i.m...
Arm/Group Description:	SOM230 LAR in a dosage of 60 mg i.m. once every 4 weeks
Overall Number of Participants Analyzed	16
Measure Type: Count of Participants Unit of Measure: Participants
Number of participants with AEs	16 100.0%
Number of participants with SAEs	7 43.8%

5.Other Pre-specified Outcome


Title	Assessment of Myasthenia Gravis (MG) Status by Determining Titin-antibody Status
Description	MG severity status is assessed by determining Titin-antibody status at...
Description	MG severity status is assessed by determining Titin-antibody status at Baseline and EOS.
Time Frame	at least 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	SOM230 LAR
Arm/Group Description:	SOM230 LAR in a dosage of 60 mg i.m...
Arm/Group Description:	SOM230 LAR in a dosage of 60 mg i.m. once every 4 weeks
Overall Number of Participants Analyzed	16
Measure Type: Count of Participants Unit of Measure: Participants
Missing data at baseline or EOS	8 50.0%
Change from negative to negative	4 25.0%
Change from negative to positive	0 0.0%
Change from positive to positive	2 12.5%
Change from positive to negative	2 12.5%

6.Other Pre-specified Outcome


Title	Assessment of Myasthenia Gravis (MG) Status by Measuring ACHR-antibody Concentrations
Description	MG severity status is assessed by measuring ACHR-antibody concentratio...
Description	MG severity status is assessed by measuring ACHR-antibody concentrations at Baseline and EOS.
Time Frame	at least 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	SOM230 LAR
Arm/Group Description:	SOM230 LAR in a dosage of 60 mg i.m...
Arm/Group Description:	SOM230 LAR in a dosage of 60 mg i.m. once every 4 weeks
Overall Number of Participants Analyzed	16
Measure Type: Count of Participants Unit of Measure: Participants
Missing data at baseline or EOS	8 50.0%
ACHR-antibody level increased	1 6.3%
ACHR-antibody level decreased	4 25.0%
ACHR-antibody level constant	3 18.8%

7.Other Pre-specified Outcome


Title	Health Related Quality of Life
Description	Health related quality o...
Description	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.
Time Frame	at least 6 months

Outcome Measure Data

Analysis Population Description

5 out of 16 patients were excluded from analysis due to missing EOS data.


Arm/Group Title	SOM230 LAR
Arm/Group Description:	SOM230 LAR in a dosage of 60 mg i.m...
Arm/Group Description:	SOM230 LAR in a dosage of 60 mg i.m. once every 4 weeks
Overall Number of Participants Analyzed	11
Mean (Standard Deviation) Unit of Measure: units on a scale
Physical function (SCR)	58.6 (28.9)
Physical function (EOS)	49.1 (25.6)
Role limitations due to physical health (SCR)	31.8 (38.9)
Role limitations due to physical health (EOS)	34.1 (45.1)
Pain (SCR)	57.3 (28.8)
Pain (EOS)	52.3 (35.7)
General health (SCR)	53.2 (12.9)
General health (EOS)	47.1 (14.5)
Energy/Fatigue (SCR)	43.6 (15.5)
Energy/Fatigue (EOS)	39.2 (21.3)
Social functioning (SCR)	61.4 (27.6)
Social functioning (EOS)	60.2 (30.5)
Role limitations due to emotional problems (SCR)	63.6 (45.8)
Role limitations due to emotional problems (EOS)	60.6 (44.3)
Emotional well-being (SCR)	60.4 (18.7)
Emotional well-being (EOS)	56.6 (20.9)
Change in health (general) (SCR)	38.6 (20.5)
Change in health (general) (EOS)	50.0 (15.8)

Adverse Events

Time Frame	Baseline, i.e. start of study drug, through study completion (EOS, including four weeks following the last dose of study drug).
Adverse Event Reporting Description	An adverse event (AE) is the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event is not considered to be related to study drug. Medical conditions/diseases present before starting study drug are only considered AE if they worsen after starting study drug.

Arm/Group Title	SOM230 LAR
Arm/Group Description	SOM230 LAR in a dosage of 60 mg i.m...
Arm/Group Description	SOM230 LAR in a dosage of 60 mg i.m. once every 4 weeks
All-Cause Mortality
	SOM230 LAR
	Affected / at Risk (%)
Total	0/16 (0.00%)
Serious Adverse Events Serious Adverse Events
	SOM230 LAR
	Affected / at Risk (%)	# Events
Total	7/16 (43.75%)
Blood and lymphatic system disorders
Anaemia ^† 1	1/16 (6.25%)	1
General disorders
Non-cardiac chest pain ^† 1	1/16 (6.25%)	1
Systemic inflammatory response syndrome ^† 1	1/16 (6.25%)	1
Infections and infestations
Pneumonia ^† 1	1/16 (6.25%)	1
Sepsis ^† 1	1/16 (6.25%)	1
Injury, poisoning and procedural complications
Foot fracture ^† 1	1/16 (6.25%)	1
Spinal fracutre ^† 1	1/16 (6.25%)	1
Metabolism and nutrition disorders
Hyperglycaemia ^† 1	3/16 (18.75%)	3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastasis ^† 1	1/16 (6.25%)	1
Tumor pain ^† 1	1/16 (6.25%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea ^† 1	1/16 (6.25%)	1
Vascular disorders
Embolism ^† 1	1/16 (6.25%)	1
Venous thrombosis ^† 1	1/16 (6.25%)	1
1 Term from vocabulary, MedDRA 19.0 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	SOM230 LAR
	Affected / at Risk (%)	# Events
Total	16/16 (100.00%)
Blood and lymphatic system disorders
Leukocytosis ^† 1	3/16 (18.75%)	3
Endocrine disorders
Cushing's syndrome ^† 1	1/16 (6.25%)	1
Eye disorders
Cataract ^† 1	2/16 (12.50%)	2
Gastrointestinal disorders
Diarrhoea ^† 1	10/16 (62.50%)	12
Abdominal pain ^† 1	3/16 (18.75%)	4
Vomiting ^† 1	2/16 (12.50%)	2
Abdominal pain upper ^† 1	1/16 (6.25%)	1
Abnormal faeces ^† 1	1/16 (6.25%)	1
Flatulence ^† 1	1/16 (6.25%)	1
Haemorrhoids ^† 1	1/16 (6.25%)	1
Nausea ^† 1	1/16 (6.25%)	1
Oral dysaesthesia ^† 1	1/16 (6.25%)	1
General disorders
Chest pain ^† 1	3/16 (18.75%)	3
Fatigue ^† 1	1/16 (6.25%)	1
Influenza like illness ^† 1	1/16 (6.25%)	1
Malaise ^† 1	1/16 (6.25%)	1
Oedema peripheral ^† 1	1/16 (6.25%)	1
Peripheral swelling ^† 1	1/16 (6.25%)	1
Pyrexia ^† 1	1/16 (6.25%)	1
Immune system disorders
Immunodeficiency ^† 1	1/16 (6.25%)	1
Infections and infestations
Cystitis ^† 1	2/16 (12.50%)	2
Nasopharyngitis ^† 1	2/16 (12.50%)	2
Skin infection ^† 1	2/16 (12.50%)	2
Bacterial infection ^† 1	1/16 (6.25%)	1
Oral candidiasis ^† 1	1/16 (6.25%)	1
Oral herpes ^† 1	1/16 (6.25%)	1
Penile infection ^† 1	1/16 (6.25%)	1
Vaginal infection ^† 1	1/16 (6.25%)	1
Injury, poisoning and procedural complications
Contusion ^† 1	1/16 (6.25%)	1
Muscle strain ^† 1	1/16 (6.25%)	1
Investigations
Gamma-glutamyltransferase increased ^† 1	2/16 (12.50%)	2
Blood creatine phosphokinase increased ^† 1	1/16 (6.25%)	1
Glycosylated haemoglobin increased ^† 1	1/16 (6.25%)	1
Troponin increased ^† 1	1/16 (6.25%)	1
Weight decreased ^† 1	1/16 (6.25%)	1
Metabolism and nutrition disorders
Hyperglycaemia ^† 1	4/16 (25.00%)	12
Diabetes mellitus ^† 1	2/16 (12.50%)	2
Gout ^† 1	1/16 (6.25%)	1
Musculoskeletal and connective tissue disorders
Muscle spasms ^† 1	3/16 (18.75%)	3
Intervertebral disc protrusion ^† 1	2/16 (12.50%)	2
Back pain ^† 1	1/16 (6.25%)	1
Neck pain ^† 1	1/16 (6.25%)	1
Pain in extremity ^† 1	1/16 (6.25%)	1
Nervous system disorders
Dizziness ^† 1	1/16 (6.25%)	1
Dysgeusia ^† 1	1/16 (6.25%)	1
Headache ^† 1	1/16 (6.25%)	1
Peripheral sensory neuropathy ^† 1	1/16 (6.25%)	1
Renal and urinary disorders
Glycosuria ^† 1	1/16 (6.25%)	1
Haematuria ^† 1	1/16 (6.25%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea ^† 1	1/16 (6.25%)	1
Cough ^† 1	1/16 (6.25%)	1
Epistaxis ^† 1	1/16 (6.25%)	2
Haemoptysis ^† 1	1/16 (6.25%)	1
Laryngeal inflammation ^† 1	1/16 (6.25%)	1
Skin and subcutaneous tissue disorders
Alopecia ^† 1	1/16 (6.25%)	1
Erythema ^† 1	1/16 (6.25%)	1
Skin hyperpigmentation ^† 1	1/16 (6.25%)	1
Vascular disorders
Flushing ^† 1	1/16 (6.25%)	1
1 Term from vocabulary, MedDRA 19.0 † Indicates events were collected by systematic assessment

Limitations and Caveats

Eval. of 3 intended secondary efficacy parameters was suspended due to scarcity of resources:

histopath. eval. of tumor samples, immunohistochem. eval. of tumor derived cells and eval. of changes in the subset composition of intratumorous T-cells

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Prof. Dr. Berthold Schalke
Organization:	Klinik und Poliklinik für Neurologie der Universitaet Regensburg
Phone:	+49 941 941 ext 3010
EMail:	berthold.schalke@medbo.de

Layout table for additonal information

Responsible Party:	Prof. Dr. Berthold Schalke, University of Regensburg
ClinicalTrials.gov Identifier:	NCT02021942
Other Study ID Numbers:	CSOM230CIC01T
First Submitted:	December 20, 2013
First Posted:	December 27, 2013
Results First Submitted:	January 31, 2017
Results First Posted:	February 5, 2018
Last Update Posted:	February 5, 2018

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