CAMPANULA: Study to Assess the Efficacy and Safety of Different Doses of BIM 23A760 in Patients With Carcinoid Syndrome

• Sponsor: Ipsen (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01018953
• Collaborator: (none)
• Enrollment: 8
• Locations: 54
• Arm: 1
• Duration (Months): 11
• Patients Per Site: 0.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of the protocol is to assess the efficacy and safety of BIM 23A760 on patient's overall satisfaction in terms of symptom relief (diarrhoea and/or flushes) in patients with carcinoid syndrome after 24 weeks of treatment.

Condition or Disease	Intervention/Treatment	Phase
Carcinoid Syndrome	Drug: BIM 23A760	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II, Open, Adaptive, Dose Escalating, Multicentre Titration Study to Assess the Efficacy and Safety of Repeated Subcutaneous Administration of Different Doses of BIM 23A760 in Patients With Carcinoid Syndrome
• Study Start Date: Feb 1, 2010
• Actual Primary Completion Date: Dec 1, 2010
• Actual Study Completion Date: Jan 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Experimental: BIM 23A760 This dose adaptive study is planned to treat up to 20 patients in each starting dose cohort, with a maximum of three starting dose cohorts. The doses planned to be assessed are 1, 2, 4, 6 and 8 mg, however, the maximum starting dose will be 4 mg. The starting dose of the first cohort will be 1 mg; the first cohort will include at least five patients. After the first fifteen patients have been treated for 4 weeks, the results will be reviewed by a Data Review Committee. An extension phase (Part B) is planned for those subjects completing the initial study and fulfilling specific eligibility criteria (symptoms control, willingness to participate, safety and tolerability).

Drug: BIM 23A760; BIM 23A760 is a solution at a concentration of 5 mg/mL ready for subcutaneous injection. BIM 23A760 dose of 1, 2, 4, 6 and 8 mg can be given to the patient according to a dose escalation and titration process. Patients will receive 24 weekly injections of BIM 23A760 during the treatment period. Patients eligible to continue the extension phase will be administered BIM 23A760 for further 52 weekly injections.

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients With a Positive Overall Satisfactory Relief of Symptoms (Diarrhoea and/or Flushes) on the Likert Scale [Week 24]

   Patient satisfaction based on a Likert scale from 0-5 (0 being not satisfied and 5 being completely satisfied)

Secondary Outcome Measures

1. Percentage of Patients With Improvement in Symptoms (Diarrhoea and/or Flushes) [Up to week 24]

2. Change in the Quality of Life (QoL) Assessment [Week 24]

3. Change in 5 Hydroxyindoleacetic Acid (5 HIAA) and Chromogranin A [Week 24]

4. Number of Subjects Reported Adverse Events, Including Any Findings From an Examination of the Injection Site(s) [Up to week 26]

5. Minimum Concentration (Cmin) BIM 23A760 Plasma Levels [At 9 timepoints up to 1 week after 24th administration in week 24]

6. Concentration at 2 Hours Postdose (C2 Hours) BIM 23A760 Plasma Levels [At 8 timepoints up to week 24]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The patient has a carcinoid syndrome defined as ≥3 stools/day and/or ≥3 flushes/week.

• The patient has elevated 5-Hydroxyindoleacetic acid (above upper limit normal).

• The patient has a well-differentiated mid-gut carcinoid tumour or serotonin secreting tumour of unknown localisation with hepatic metastasis.

Exclusion Criteria:

• The patient has undergone surgery related to a neuroendocrine tumour (NET) within 4 weeks prior to study entry or has surgery planned during the study.

• The patient has received short acting somatostatin analogues (SSAs) within 2 weeks before study entry or has received short acting SSAs for more than 3 months.

• The patient has received a radiolabelled SSA at any time before study entry.

• The patient has received long acting SSAs under certain circumstances.

• The patient has previously received any specific anti tumour treatment such as chemotherapy, (chemo)embolisation, radiotherapy or interferon in the last 6 months.

• The patient has signs or symptoms of cardiac insufficiency.

• The patient has an ejection fraction <40% and/or clinically severe cardiac valvular regurgitation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital, Internal Medicine - Oncology	Vienna		Austria	A-9010
2	UZ Antwerpen	Edegem		Belgium	2650
3	UZ Gent	Gent		Belgium	9000
4	UZ GAsthuisberg	Leuven		Belgium	3000
5	Fakultní nemocnice Hradec Králové	Hradec Králové		Czechia	500 05
6	Fakultní nemocnice Olomouc	Olomouc		Czechia	775 20
7	Fakultní nemocnice Na Bulovce, Ústav radiační onkologie	Praha 8		Czechia	180 81
8	Helsinki Central University Hospital	Helsinki		Finland	FIN-00029
9	Turku University Hospital	Turku		Finland	FIN-20521
10	Service de Gastroentérologie	Clichy		France
11	Unité d'Oncologie Médicale	Lyon		France	Cedex 03
12	Institut Paoli Calmette	Marseille		France	13009
13	Centre René Gauducheau	Nantes		France	44805
14	Unité de Gastro-Entérologie	Villejuif		France
15	Charite Universitätsmedizin Berlin, Campus Virchow-Klinikum	Berlin		Germany	13353
16	Universitätsklinikum Heidelberg	Heidelberg		Germany	69120
17	Universitätsmedizin Mainz	Mainz		Germany	55131
18	St James's Hospital	Dublin		Ireland
19	Hadassah Medical Organization	Jerusalem		Israel	91120
20	Rabin Medical Center	Petah Tikva		Israel	49100
21	Università degli Studi di Bologna, Policlinico S. Orsola-Malpighi	Bologna		Italy	40138
22	Istituti Ospitalieri di Cremona	Cremona		Italy	26100
23	Ospedale San Martino	Genova		Italy	16132
24	AO Universitaria Policlinico di Modena	Modena		Italy	41124
25	Ospedale S.Maria della Misericordia	Perugia		Italy	06132
26	Università degli Studi di Roma "La Sapienza", II Facoltà di Medicina e Chirurgia, Ospedale Sant'Andrea	Roma		Italy	00109
27	Latvian Oncology centre of Riga Eastern Clinical University Hospital	Riga		Latvia	LV-1079
28	Vidzemes Hospital	Valmiera		Latvia	LV-4201
29	UMCG	Groningen		Netherlands	9700
30	Erasmus MC	Rotterdam		Netherlands	3015
31	Centrum Onkologii Instytut im.M. Sklodowskiej-Curie oddzial w Gliwicach	Gliwice		Poland	44-101
32	Szpital Uniwersytecki w Krakowie	Krakow		Poland	, 31-501
33	Instytut im Marii Sklodowskiej Curie	Warszawa		Poland	02-785
34	Samodzielny Publiczny Szpital Kliniczny nr 1	Wroclaw, 50-367		Poland	50-367
35	Altay Regional Oncology dispensary	Barnaul		Russian Federation	656052
36	Republican Clinical Oncology dispensary of the Ministry of Health of Republic of Tatarstan	Kazan		Russian Federation	420111
37	Non-state Institution of Public health "Central Clinical hospital # 1, public corporation "Russian railways"	Moscow		Russian Federation	125367
38	St-Petersburg State Medical University named after academician Pavlov I.P.	Saint Petersburg		Russian Federation	197089
39	St-Petersburg State Institution of Public Health City Clinical Oncology dispensary	Saint Petersburg		Russian Federation	198255
40	Tula Regional Oncology Dispensary	Tula		Russian Federation	300053
41	Voronezh Regional Clinical Oncology Dispensary	Voronezh		Russian Federation	394000
42	Narodny onkologicky ustav	Bratislava		Slovakia	83310
43	Martinska fakultna nemocnice	Martin		Slovakia	03601
44	Hospital Universitario Ramon y Cajal	Madrid		Spain	28034
45	Hospital 12 de Octubre	Madrid		Spain	28041
46	Hospital Universitario Son Dureta	Palma de Mallorca		Spain	07014
47	Akademiska Hospital, Dept of Oncology & Endocrinology	Uppsala		Sweden	751 85
48	Donetsk National Medical University named after M. Gorkiy, Donetsk Regional Antitumor Center	Donetsk		Ukraine	83092
49	Uzhgorod national university, Postgraduate faculty, Uzhgorod Central City Clinical Hospital	Uzhgorod		Ukraine	88000
50	University Hospital Aintree	Liverpool		United Kingdom	L9 7AL
51	St Bartholomew's Hospital	London		United Kingdom	EC1A 7BE
52	Royal Free Hospital	London		United Kingdom	NW3 2QG
53	Christie Hospital and Holt Radium Institute	Manchester		United Kingdom	M20 4BX
54	Royal Preston Hospital, Sharoe Green Lane, Lancashire	Preston		United Kingdom	PR2 9HT

Sponsors and Collaborators

• Ipsen

Investigators

• Study Director: Ipsen Medical Director, Ipsen

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ipsen
• ClinicalTrials.gov Identifier: NCT01018953
• Other Study ID Numbers: 8-55-52060-004; 2009-013222-16
• First Posted: Nov 25, 2009
• Last Update Posted: Nov 20, 2020
• Last Verified: Nov 1, 2020

• Additional relevant MeSH terms: Carcinoid Tumor; Malignant Carcinoid Syndrome; Syndrome; Serotonin Syndrome

Study Results

Participant Flow

Recruitment Details	This study was terminated prematurely. Only 8 patients were treated in part A and no patients participated in part B.
Pre-assignment Detail	Patients screened were 15 and not treated were 7 (2 subjects were not included due to early termination of study by sponsor and 5 subjects failed to meet inclusion criteria).

Arm/Group Title	BIM 23A760
Arm/Group Description	This dose adaptive study was planned to treat up to 20 patients in each starting dose cohort, with a maximum of three starting dose cohorts. The doses planned to be assessed were 1, 2, 4, 6 and 8 mg; however, the maximum starting dose was 4 mg. The starting dose of the first cohort was 1 mg and the first cohort would include at least five patients. After the first 15 patients were treated for 4 weeks, the results were to be reviewed by a Data Review Committee. An extension phase (Part B) was planned for those subjects completing the initial study and fulfilling specific eligibility criteria (symptoms control, willingness to participate, safety and tolerability). BIM 23A760 was a solution at a concentration of 5 mg/mL ready for subcutaneous injection. BIM 23A760 doses of 1, 2, 4, 6 and 8 mg were to be given to the patient according to a dose escalation and titration process. Patients would have received 24 weekly injections of BIM 23A760 during the treatment period.
Period Title: Overall Study
STARTED	8
BIM 23A760 1 mg	3
BIM 23A760 2 mg	2
BIM 23A760 4 mg	3
COMPLETED	0
NOT COMPLETED	8

Baseline Characteristics

Arm/Group Title	BIM 23A760
Arm/Group Description	This dose adaptive study was planned to treat up to 20 patients in each starting dose cohort, with a maximum of three starting dose cohorts. The doses planned to be assessed were 1, 2, 4, 6 and 8 mg; however, the maximum starting dose was 4 mg. The starting dose of the first cohort was 1 mg and the first cohort would include at least five patients. After the first 15 patients were treated for 4 weeks, the results were to be reviewed by a Data Review Committee. An extension phase (Part B) was planned for those subjects completing the initial study and fulfilling specific eligibility criteria (symptoms control, willingness to participate, safety and tolerability). BIM 23A760 was a solution at a concentration of 5 mg/mL ready for subcutaneous injection. BIM 23A760 doses of 1, 2, 4, 6 and 8 mg were to be given to the patient according to a dose escalation and titration process. Patients would have received 24 weekly injections of BIM 23A760 during the treatment period.
Overall Participants	8
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.1 (6.88)
Age, Customized (participants) [Number]
Between 18 and 75 years	8 100%
Sex: Female, Male (Count of Participants)
Female	6 75%
Male	2 25%
Race/Ethnicity, Customized (participants) [Number]
Caucasian/ White	8 100%
Region of Enrollment (participants) [Number]
Russian Federation	1 12.5%
United Kingdom	2 25%
Netherlands	1 12.5%
Belgium	1 12.5%
Ireland	1 12.5%
Finland	1 12.5%
Germany	1 12.5%
Diabetic status (participants) [Number]
Diabetic	0 0%
Nondiabetic	8 100%
Post-menopausal status (participants) [Number]
Yes	6 75%
No	0 0%
N/A - Not applicable	2 25%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients With a Positive Overall Satisfactory Relief of Symptoms (Diarrhoea and/or Flushes) on the Likert Scale
Description	Patient satisfaction based on a Likert scale from 0-5 (0 being not satisfied and 5 being completely satisfied)
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Study was prematurely terminated and no data was collected/analyzed for this outcome measure.

Arm/Group Title	BIM 23A760
Arm/Group Description	This dose adaptive study was planned to treat up to 20 patients in each starting dose cohort, with a maximum of three starting dose cohorts. The doses planned to be assessed were 1, 2, 4, 6 and 8 mg; however, the maximum starting dose was 4 mg. The starting dose of the first cohort was 1 mg and the first cohort would include at least five patients. After the first 15 patients were treated for 4 weeks, the results were to be reviewed by a Data Review Committee. An extension phase (Part B) was planned for those subjects completing the initial study and fulfilling specific eligibility criteria (symptoms control, willingness to participate, safety and tolerability). BIM 23A760 was a solution at a concentration of 5 mg/mL ready for subcutaneous injection. BIM 23A760 doses of 1, 2, 4, 6 and 8 mg were to be given to the patient according to a dose escalation and titration process. Patients would have received 24 weekly injections of BIM 23A760 during the treatment period.
Measure Participants	0

2. Secondary Outcome

Title	Percentage of Patients With Improvement in Symptoms (Diarrhoea and/or Flushes)
Time Frame	Up to week 24

Outcome Measure Data

Analysis Population Description

Study was prematurely terminated and no data was collected/analyzed for this outcome measure.

Arm/Group Title	BIM 23A760
Arm/Group Description
Measure Participants	0

3. Secondary Outcome

Title	Change in the Quality of Life (QoL) Assessment
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Study was prematurely terminated and no data was collected/analyzed for this outcome measure.

Arm/Group Title	BIM 23A760
Arm/Group Description
Measure Participants	0

4. Secondary Outcome

Title	Change in 5 Hydroxyindoleacetic Acid (5 HIAA) and Chromogranin A
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Study was prematurely terminated and no data was collected/analyzed for this outcome measure.

Arm/Group Title	BIM 23A760
Arm/Group Description
Measure Participants	0

5. Secondary Outcome

Title	Number of Subjects Reported Adverse Events, Including Any Findings From an Examination of the Injection Site(s)
Time Frame	Up to week 26

Outcome Measure Data

Analysis Population Description

Both ITT (Intent-To-Treat) and safety populations were the same analysis group. Treatment emergent adverse events (TEAE) reported by 2 or more patients (safety population) by primary system organ class.

Arm/Group Title	BIM 23A760
Arm/Group Description	This dose adaptive study was planned to treat up to 20 patients in each starting dose cohort, with a maximum of three starting dose cohorts. The doses planned to be assessed were 1, 2, 4, 6 and 8 mg; however, the maximum starting dose was 4 mg. The starting dose of the first cohort was 1 mg and the first cohort would include at least five patients. After the first 15 patients were treated for 4 weeks, the results were to be reviewed by a Data Review Committee. An extension phase (Part B) was planned for those subjects completing the initial study and fulfilling specific eligibility criteria (symptoms control, willingness to participate, safety and tolerability). BIM 23A760 was a solution at a concentration of 5 mg/mL ready for subcutaneous injection. BIM 23A760 doses of 1, 2, 4, 6 and 8 mg were to be given to the patient according to a dose escalation and titration process. Patients would have received 24 weekly injections of BIM 23A760 during the treatment period.
Measure Participants	8
General Disorders & Administration Site Condition	5 62.5%
Gastrointestinal Disorder	4 50%
Nervous System Disorders	3 37.5%
Infections and Infestations	2 25%
Metabolism and Nutritional Disorders	2 25%
Neoplasms Benign, Malignant and unspecified	2 25%
Reproductive System and Breast Disorders	2 25%

6. Secondary Outcome

Title	Minimum Concentration (Cmin) BIM 23A760 Plasma Levels
Time Frame	At 9 timepoints up to 1 week after 24th administration in week 24

Outcome Measure Data

Analysis Population Description

Study was prematurely terminated and no data was collected/analyzed for this outcome measure.

Arm/Group Title	BIM 23A760
Arm/Group Description
Measure Participants	0

7. Secondary Outcome

Title	Concentration at 2 Hours Postdose (C2 Hours) BIM 23A760 Plasma Levels
Time Frame	At 8 timepoints up to week 24

Outcome Measure Data

Analysis Population Description

Study was prematurely terminated and no data was collected/analyzed for this outcome measure.

Arm/Group Title	BIM 23A760
Arm/Group Description
Measure Participants	0

Adverse Events

Time Frame	Up to week 26
Adverse Event Reporting Description	Dose received prior to AE onset. Two serious adverse events (SAEs) 'Confusional State' and 'Nausea' were not included as they occurred during screening phase, before starting study drug.
Arm/Group Title	BIM 23A760
Arm/Group Description	This dose adaptive study was planned to treat up to 20 patients in each starting dose cohort, with a maximum of three starting dose cohorts. The doses planned to be assessed were 1, 2, 4, 6 and 8 mg; however, the maximum starting dose was 4 mg. The starting dose of the first cohort was 1 mg and the first cohort would include at least five patients. After the first 15 patients were treated for 4 weeks, the results were to be reviewed by a Data Review Committee. An extension phase (Part B) was planned for those subjects completing the initial study and fulfilling specific eligibility criteria (symptoms control, willingness to participate, safety and tolerability). BIM 23A760 was a solution at a concentration of 5 mg/mL ready for subcutaneous injection. BIM 23A760 doses of 1, 2, 4, 6 and 8 mg were to be given to the patient according to a dose escalation and titration process. Patients would have received 24 weekly injections of BIM 23A760 during the treatment period.
All Cause Mortality
	BIM 23A760
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	BIM 23A760
	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm progression	1/8 (12.5%)	1
Other (Not Including Serious) Adverse Events
	BIM 23A760
	Affected / at Risk (%)	# Events
Total	6/8 (75%)
Eye disorders
Vision blurred	1/8 (12.5%)	1
Gastrointestinal disorders
Nausea	3/8 (37.5%)	3
Abdominal pain	2/8 (25%)	2
Constipation	2/8 (25%)	2
Vomiting	2/8 (25%)	3
Abdominal distension	1/8 (12.5%)	1
Diarrhoea	1/8 (12.5%)	1
Dyspepsia	1/8 (12.5%)	1
Mucous stools	1/8 (12.5%)	1
General disorders
Injection site erythema	2/8 (25%)	2
Fatigue	1/8 (12.5%)	1
Injection site inflammation	1/8 (12.5%)	1
Injection site pain	1/8 (12.5%)	3
Injection site pruritus	1/8 (12.5%)	1
Injection site reaction	1/8 (12.5%)	1
Oedema	1/8 (12.5%)	1
Infections and infestations
Nasopharyngitis	1/8 (12.5%)	1
Sinusitis	1/8 (12.5%)	1
Injury, poisoning and procedural complications
Procedural pain	1/8 (12.5%)	1
Metabolism and nutrition disorders
Decreased appetite	2/8 (25%)	3
Hypoalbuminaemia	1/8 (12.5%)	1
Musculoskeletal and connective tissue disorders
Groin pain	1/8 (12.5%)	1
Systemic lupus erythematosus	1/8 (12.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to liver	1/8 (12.5%)	1
Metastases to peripheral vascular system	1/8 (12.5%)	1
Nervous system disorders
Dizziness	2/8 (25%)	2
Headache	1/8 (12.5%)	1
Lethargy	1/8 (12.5%)	1
Psychiatric disorders
Anxiety	1/8 (12.5%)	1
Reproductive system and breast disorders
Breast pain	1/8 (12.5%)	1
Pelvic floor muscle weakness	1/8 (12.5%)	1
Vulvovaginal dryness	1/8 (12.5%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/8 (12.5%)	1
Skin and subcutaneous tissue disorders
Dry skin	1/8 (12.5%)	1
Erythema	1/8 (12.5%)	1
Night sweats	1/8 (12.5%)	1
Vascular disorders
Flushing	1/8 (12.5%)	1

Limitations/Caveats

Due to premature termination of the study, no data was collected/analyzed and no patient participated in Part B.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.