HOSCAR: Study to Evaluate the Efficacy and Safety of Sandostatin LAR at High Dose or in Combination Either With GH-receptor Antagonist or Dopamine-agonist in Acromegalic Patients

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01278342
• Collaborator: (none)
• Enrollment: 70
• Locations: 20
• Arms: 3
• Duration (Months): 38
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will assess the efficacy of 8 months treatment of Sandostatin® LAR® High Dose monotherapy or Sandostatin® LAR® High Dose in combination either with growth hormone antagonist or dopamine agonist to control biochemical parameters (GH and insulin-like growth factor I [IGF I]) of acromegalic patients not achieving biochemical normalization at conventional regimen.

Condition or Disease	Intervention/Treatment	Phase
Acromegaly	Drug: Sandostatin LAR; Drug: pegvisomant; Drug: cabergoline	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Two-step, Multicenter European Study to Evaluate the Efficacy and Safety of Sandostatin LAR at High Dose or in Combination Either With GH-receptor Antagonist or Dopamine-agonist in Acromegalic Patients Not Adequately Controlled by Conventional Regimen
• Study Start Date: Sep 1, 2006
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Nov 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Sandostatin LAR high dose Alone All patients were treated with Sandostatin LAR 40 mg i.m. every 28 days for 3 months. Following biochemical assessment, patients with controlled GH and IGF-I after 3 months of Sandostatin LAR monotherapy continued to receive Sandostatin LAR 40 mg i.m. every 28 days for an additional 4 months.	Drug: Sandostatin LAR; 40 mg intramuscular (i.m.) every 28 days for 3 months; Other Names: octreotide acetate
Experimental: Sandostatin LAR high dose + Pegvisomat All patients were treated with Sandostatin LAR 40 mg i.m. every 28 days for 3 months. Following biochemical assessment, patients with uncontrolled GH and or IGF-I received Sandostatin LAR40 mg every 28 days in combination with weekly doses of pegvisomant 70 mg subcutaneously (s.c.) for a further 4 months	Drug: Sandostatin LAR; 40 mg intramuscular (i.m.) every 28 days for 3 months; Other Names: octreotide acetate ; Drug: pegvisomant; Weekly doses of pegvisomant 70 mg subcutaneously (s.c.) for 4 months given with Sandostatin LAR 40 mg intramuscular (i.m.) every 28 days for 4 months; Other Names: Somavert octreotide acaetate
Experimental: Sandostatin LAR high dose + Cabergoline All patients were treated with Sandostatin LAR 40 mg i.m. every 28 days for 3 months. Following biochemical assessment, patients with uncontrolled GH and or IGF-I received Sandostatin LAR 40 mg every 28 days in combination with weekly cabergoline for a further 4 months, with cabergoline doses as follows: st week: 0.25 mg twice a week (0.50 mg/week) nd week: 0.50 mg/week twice a week (1 mg/week) rd week: 0.50 mg four times a week (2 mg/week) th week: 0.50 mg daily (3.5 mg/week) Subsequent 3 months: 0.50 mg daily (3.5 mg/week)	Drug: Sandostatin LAR; 40 mg intramuscular (i.m.) every 28 days for 3 months; Other Names: octreotide acetate ; Drug: cabergoline; Weekly cabergoline for 4 months, with weekly doses of Sandostatin LAR 40 mg intramuscular (i.m.) every 28 days for 4 months. Cabergoline doses as follows: st week: 0.25 mg twice a week (0.50 mg/week) nd week: 0.50 mg/week twice a week (1 mg/week) rd week: 0.50 mg four times a week (2 mg/week) th week: 0.50 mg daily (3.5 mg/week) Subsequent 3 months: 0.50 mg daily (3.5 mg/week); Other Names: Dostinex octreotide acetate

Outcome Measures

Primary Outcome Measures

1. The Percentage of Participants With Complete Response (CR) at 8 Months [From Baseline to 8 months]

   A patient was classified as a Complete Responder (CR) if both biochemical parameters were controlled at the end of 8 months of treatment: Mean 1 hour GH < 2.5µg/L (according to Central Laboratory); and IGF-I within the Central Laboratory Normal Range (for age and gender).

Secondary Outcome Measures

1. The Percentage of Participants With Complete Response (CR) At 3 Months [From Baseline to 3 months]

   A patient was classified as CR if both biochemical parameters were controlled at the end of 3 months of treatment: Mean 1 hour GH < 2.5µg/L (according to Central Laboratory); and IGF-I within the Central Laboratory Normal Range (for age and gender)

2. The Percentage of Participants With Partial Response (PR) at 8 Months [From Baseline to 8 months]

   Patients who met one of the following criteria at the end of 8 months of treatment were defined as Partial Responders, regardless of the treatment. Mean 1 hour GH > 2.5 µg/L and < 5 µg/L and either a decrease in IGF-I of at least 50% compared to baseline or IGF-I within normal range. Mean 1 hour GH < 2.5 µg/L and a decrease in IGF-I of at least 50% compared to baseline and IGF-I outside normal range.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient with a biochemically documented active acromegaly, not adequately controlled by somatostatin-analogues at conventional regimen as follow : mean 1-hour GH > 2.5 ng/mL and elevated IGF-1 (adjusted for age and gender)

• Patient with reduction of either mean fasting GH at least 50% or IGF-1 at least 25% from any medical pretreatment level

• Patient currently receiving somatostatin-analogues at conventional regimen (maximum registered dose) for at least 6 months before inclusion

Exclusion Criteria:

• Newly diagnosed or previously medically untreated acromegalic patient

• Concomitant treatment with GH-receptor antagonist

• Concomitant treatment with dopamine-agonist

• Symptomatic cholelithiasis or choledocolithiasis

• Liver transaminases (ALT, AST) elevated, but > 3 times upper normal limit (according to local laboratory)

• Previous gamma-knife radiotherapy for treatment of acromegaly

• Compression of the optic chiasm causing visual field defect

• Any medical conditions contraindicated in the Summary of Product Characteristic (SPC) of all drugs

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Brest Cedex		France	29609
2	Novartis Investigative Site	Bron Cedex		France	69677
3	Novartis Investigative Site	Kremlin-Bicetre		France	94275
4	Novartis Investigative Site	Nice		France	06202
5	Novartis Investigative Site	Nimes		France	30029
6	Novartis Investigative Site	Pessac		France	33604
7	Novartis Investigative Site	Toulouse		France	31059
8	Novartis Investigative Site	Genova		Italy	16132
9	Novarts Investigative Site	Naples		Italy
10	Novartis Investigative Site	Napoli		Italy	80131
11	Novartis Investigative Site	Padova		Italy
12	Novartis Investigative Site	Perugia		Italy	06126
13	Novartis Investigative Site	Pisa		Italy	56124
14	Novartis Investigative Site	Torino		Italy	10126
15	Novartis Investigative Site	Lodz		Poland	91-425
16	Novartis Investigative Site	Warszawa		Poland
17	Novartis Investigative Site	Wroclaw		Poland
18	Novartis Investigative Site	Zabrze		Poland	41-800
19	Novartis Investigative Site	Porto		Portugal	4200-319
20	Novartis Investigative Site	Lausanne		Switzerland	CH-1011

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT01278342
• Other Study ID Numbers: CSMS995BIC03; 2005-005852-42
• First Posted: Jan 17, 2011
• Last Update Posted: Mar 3, 2017
• Last Verified: Feb 1, 2017

• Keywords provided by , ,: Sandostatin LAR; High Dose; GH-receptor antagonist; combination with dopamine-agonist; acromegalic patients; octreotide acetate; Somavert; Dostinex; pegvisomant; cabergoline; not adequately controlled; active acromegaly
• Additional relevant MeSH terms: Acromegaly; Octreotide; Cabergoline

Study Results

Participant Flow

Arm/Group Title	Sandostatin LAR High Dose Alone	Sandostatin LAR High Dose + Pegvisomat	Sandostatin LAR High Dose + Cabergoline
Arm/Group Description	All patients were treated with Sandostatin LAR 40 mg i.m. every 28 days for 3 months. Following biochemical assessment, patients with controlled GH and IGF-I after 3 months of Sandostatin LAR monotherapy continued to receive Sandostatin LAR 40 mg i.m. every 28 days for an additional 4 months.	All patients were treated with Sandostatin LAR 40 mg i.m. every 28 days for 3 months. Following biochemical assessment, patients with uncontrolled GH and/or IGF-I, were randomized to receive Sandostatin LAR 40 mg every 28 days in combination with weekly doses of Pegvisomant 70 mg subcutaneously (s.c.) for a further 4 months.	All patients were treated with Sandostatin LAR 40 mg i.m. every 28 days for 3 months. Following biochemical assessment, patients with uncontrolled GH and/or IGF-I, were randomized to receive Sandostatin LAR 40 mg every 28 days in combination with weekly doses of Cabergoline for a further 4 months, with Cabergoline doses as follows: 1st week: 0.25 mg twice a week (0.50 mg/week) 2nd week: 0.50 mg/week twice a week (1 mg/week) 3rd week: 0.50 mg four times a week (2 mg/week) 4th week: 0.50 mg daily (3.5 mg/week) Subsequent 3 months: 0.50 mg daily (3.5 mg/week)
Period Title: Overall Study
STARTED	7	31	32
COMPLETED	3	30	32
NOT COMPLETED	4	1	0

Baseline Characteristics

Arm/Group Title	Sandostatin LAR High Dose Alone	Sandostatin LAR High Dose + Pegvisomat	Sandostatin LAR High Dose + Cabergoline	Total
Arm/Group Description	All patients were treated with Sandostatin LAR 40 mg i.m. every 28 days for 3 months. Following biochemical assessment, patients with controlled GH and IGF-I after 3 months of Sandostatin LAR monotherapy continued to receive Sandostatin LAR 40 mg i.m. every 28 days for an additional 4 months.	All patients were treated with Sandostatin LAR 40 mg i.m. every 28 days for 3 months. Following biochemical assessment, patients with uncontrolled GH and/or IGF-I, were randomized to receive Sandostatin LAR 40 mg every 28 days in combination with weekly doses of Pegvisomant 70 mg subcutaneously (s.c.) for a further 4 months.	All patients were treated with Sandostatin LAR 40 mg i.m. every 28 days for 3 months. Following biochemical assessment, patients with uncontrolled GH and/or IGF-I, were randomized to receive Sandostatin LAR 40 mg every 28 days in combination with weekly doses of Cabergoline for a further 4 months, with Cabergoline doses as follows: 1st week: 0.25 mg twice a week (0.50 mg/week) 2nd week: 0.50 mg/week twice a week (1 mg/week) 3rd week: 0.50 mg four times a week (2 mg/week) 4th week: 0.50 mg daily (3.5 mg/week) Subsequent 3 months: 0.50 mg daily (3.5 mg/week)	Total of all reporting groups
Overall Participants	7	31	32	70
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.9 (7.71)	44.6 (10.54)	49.3 (10.50)	48.1 (10.90)
Sex: Female, Male (Count of Participants)
Female	3 42.9%	17 54.8%	18 56.3%	38 54.3%
Male	4 57.1%	14 45.2%	14 43.8%	32 45.7%

Outcome Measures

1. Primary Outcome

Title	The Percentage of Participants With Complete Response (CR) at 8 Months
Description	A patient was classified as a Complete Responder (CR) if both biochemical parameters were controlled at the end of 8 months of treatment: Mean 1 hour GH < 2.5µg/L (according to Central Laboratory); and IGF-I within the Central Laboratory Normal Range (for age and gender).
Time Frame	From Baseline to 8 months

Outcome Measure Data

Analysis Population Description

Intent-to-Treat population - all participants receiving at least one dose of Sandostatin LAR

Arm/Group Title	Sandostatin LAR High Dose Alone	Sandostatin LAR High Dose + Pegvisomat	Sandostatin LAR High Dose + Cabergoline
Arm/Group Description	All patients were treated with Sandostatin LAR 40 mg i.m. every 28 days for 3 months. Following biochemical assessment, patients with controlled GH and IGF-I after 3 months of Sandostatin LAR monotherapy continued to receive Sandostatin LAR 40 mg i.m. every 28 days for an additional 4 months.	All patients were treated with Sandostatin LAR 40 mg i.m. every 28 days for 3 months. Following biochemical assessment, patients with uncontrolled GH and/or IGF-I, were randomized to receive Sandostatin LAR 40 mg every 28 days in combination with weekly doses of Pegvisomant 70 mg subcutaneously (s.c.) for a further 4 months.	All patients were treated with Sandostatin LAR 40 mg i.m. every 28 days for 3 months. Following biochemical assessment, patients with uncontrolled GH and/or IGF-I, were randomized to receive Sandostatin LAR 40 mg every 28 days in combination with weekly doses of Cabergoline for a further 4 months, with Cabergoline doses as follows: 1st week: 0.25 mg twice a week (0.50 mg/week) 2nd week: 0.50 mg/week twice a week (1 mg/week) 3rd week: 0.50 mg four times a week (2 mg/week) 4th week: 0.50 mg daily (3.5 mg/week) Subsequent 3 months: 0.50 mg daily (3.5 mg/week)
Measure Participants	7	31	32
Number (95% Confidence Interval) [percent]	25	0	9.4

2. Secondary Outcome

Title	The Percentage of Participants With Complete Response (CR) At 3 Months
Description	A patient was classified as CR if both biochemical parameters were controlled at the end of 3 months of treatment: Mean 1 hour GH < 2.5µg/L (according to Central Laboratory); and IGF-I within the Central Laboratory Normal Range (for age and gender)
Time Frame	From Baseline to 3 months

Outcome Measure Data

Analysis Population Description

Intent-to-Treat population - all participants receiving at least one dose of Sandostatin LAR

Arm/Group Title	Sandostatin LAR High Dose Alone	Sandostatin LAR High Dose + Pegvisomat	Sandostatin LAR High Dose + Cabergoline
Arm/Group Description	All patients were treated with Sandostatin LAR 40 mg i.m. every 28 days for 3 months. Following biochemical assessment, patients with controlled GH and IGF-I after 3 months of Sandostatin LAR monotherapy continued to receive Sandostatin LAR 40 mg i.m. every 28 days for an additional 4 months.	All patients were treated with Sandostatin LAR 40 mg i.m. every 28 days for 3 months. Following biochemical assessment, patients with uncontrolled GH and/or IGF-I, were randomized to receive Sandostatin LAR 40 mg every 28 days in combination with weekly doses of Pegvisomant 70 mg subcutaneously (s.c.) for a further 4 months.	All patients were treated with Sandostatin LAR 40 mg i.m. every 28 days for 3 months. Following biochemical assessment, patients with uncontrolled GH and/or IGF-I, were randomized to receive Sandostatin LAR 40 mg every 28 days in combination with weekly doses of Cabergoline for a further 4 months, with Cabergoline doses as follows: 1st week: 0.25 mg twice a week (0.50 mg/week) 2nd week: 0.50 mg/week twice a week (1 mg/week) 3rd week: 0.50 mg four times a week (2 mg/week) 4th week: 0.50 mg daily (3.5 mg/week) Subsequent 3 months: 0.50 mg daily (3.5 mg/week)
Measure Participants	7	31	32
Number (95% Confidence Interval) [percent]	60	0	0

3. Secondary Outcome

Title	The Percentage of Participants With Partial Response (PR) at 8 Months
Description	Patients who met one of the following criteria at the end of 8 months of treatment were defined as Partial Responders, regardless of the treatment. Mean 1 hour GH > 2.5 µg/L and < 5 µg/L and either a decrease in IGF-I of at least 50% compared to baseline or IGF-I within normal range. Mean 1 hour GH < 2.5 µg/L and a decrease in IGF-I of at least 50% compared to baseline and IGF-I outside normal range.
Time Frame	From Baseline to 8 months

Outcome Measure Data

Analysis Population Description

Intent-to-Treat population - all participants receiving at least one dose of Sandostatin LAR

Arm/Group Title	Sandostatin LAR High Dose Alone	Sandostatin LAR High Dose + Pegvisomat	Sandostatin LAR High Dose + Cabergoline
Arm/Group Description	All patients were treated with Sandostatin LAR 40 mg i.m. every 28 days for 3 months. Following biochemical assessment, patients with controlled GH and IGF-I after 3 months of Sandostatin LAR monotherapy continued to receive Sandostatin LAR 40 mg i.m. every 28 days for an additional 4 months.	All patients were treated with Sandostatin LAR 40 mg i.m. every 28 days for 3 months. Following biochemical assessment, patients with uncontrolled GH and/or IGF-I, were randomized to receive Sandostatin LAR 40 mg every 28 days in combination with weekly doses of Pegvisomant 70 mg subcutaneously (s.c.) for a further 4 months.	All patients were treated with Sandostatin LAR 40 mg i.m. every 28 days for 3 months. Following biochemical assessment, patients with uncontrolled GH and/or IGF-I, were randomized to receive Sandostatin LAR 40 mg every 28 days in combination with weekly doses of Cabergoline for a further 4 months, with Cabergoline doses as follows: 1st week: 0.25 mg twice a week (0.50 mg/week) 2nd week: 0.50 mg/week twice a week (1 mg/week) 3rd week: 0.50 mg four times a week (2 mg/week) 4th week: 0.50 mg daily (3.5 mg/week) Subsequent 3 months: 0.50 mg daily (3.5 mg/week)
Measure Participants	7	31	32
Number (95% Confidence Interval) [percent]	25	22.6	21.9

Adverse Events

Arm/Group Title	Sandostatin LAR High Dose Alone		Sandostatin LAR High Dose + Pegvisomant		Sandostatin LAR High Dose + Cabergoline
Arm/Group Description	All patients were treated with Sandostatin LAR 40 mg i.m. every 28 days for 3 months. Following biochemical assessment, patients with controlled GH and IGF-I after 3 months of Sandostatin LAR monotherapy continued to receive Sandostatin LAR 40 mg i.m. every 28 days for an additional 4 months		All patients were treated with Sandostatin LAR 40 mg i.m. every 28 days for 3 months. Following biochemical assessment, patients with uncontrolled GH and/or IGF-I, were randomized to receive Sandostatin LAR 40 mg every 28 days in combination with weekly doses of Pegvisomant 70 mg subcutaneously (s.c.) for a further 4 months.		All patients were treated with Sandostatin LAR 40 mg i.m. every 28 days for 3 months. Following biochemical assessment, patients with uncontrolled GH and/or IGF-I, were randomized to receive Sandostatin LAR 40 mg every 28 days in combination with weekly doses of Cabergoline for a further 4 months, with Cabergoline doses as follows: 1st week: 0.25 mg twice a week (0.50 mg/week) 2nd week: 0.50 mg/week twice a week (1 mg/week) 3rd week: 0.50 mg four times a week (2 mg/week) 4th week: 0.50 mg daily (3.5 mg/week) Subsequent 3 months: 0.50 mg daily (3.5 mg/week)
All Cause Mortality
	Sandostatin LAR High Dose Alone		Sandostatin LAR High Dose + Pegvisomant		Sandostatin LAR High Dose + Cabergoline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Sandostatin LAR High Dose Alone		Sandostatin LAR High Dose + Pegvisomant		Sandostatin LAR High Dose + Cabergoline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		1/32 (3.1%)		2/31 (6.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cell carcinoma	0/7 (0%)		0/32 (0%)		1/31 (3.2%)
Nervous system disorders
IIIrd nerve paralysis	0/7 (0%)		0/32 (0%)		1/31 (3.2%)
Vascular disorders
Deep vein thrombosis	0/7 (0%)		1/32 (3.1%)		0/31 (0%)
Other (Not Including Serious) Adverse Events
	Sandostatin LAR High Dose Alone		Sandostatin LAR High Dose + Pegvisomant		Sandostatin LAR High Dose + Cabergoline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/7 (57.1%)		15/32 (46.9%)		12/31 (38.7%)
Ear and labyrinth disorders
Vertigo	0/7 (0%)		1/32 (3.1%)		2/31 (6.5%)
Gastrointestinal disorders
Abdominal pain	0/7 (0%)		2/32 (6.3%)		3/31 (9.7%)
Diarrhoea	0/7 (0%)		4/32 (12.5%)		3/31 (9.7%)
Dyspepsia	0/7 (0%)		2/32 (6.3%)		0/31 (0%)
Flatulence	0/7 (0%)		2/32 (6.3%)		0/31 (0%)
Infections and infestations
Nasopharyngitis	1/7 (14.3%)		2/32 (6.3%)		1/31 (3.2%)
Pneumonia	1/7 (14.3%)		0/32 (0%)		0/31 (0%)
Investigations
Blood glucose increased	0/7 (0%)		4/32 (12.5%)		0/31 (0%)
Blood insulin decreased	1/7 (14.3%)		0/32 (0%)		0/31 (0%)
Glycosylated haemoglobin increased	0/7 (0%)		2/32 (6.3%)		0/31 (0%)
Metabolism and nutrition disorders
Diabetes mellitus	0/7 (0%)		2/32 (6.3%)		1/31 (3.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/7 (0%)		0/32 (0%)		3/31 (9.7%)
Back pain	0/7 (0%)		1/32 (3.1%)		3/31 (9.7%)
Nervous system disorders
Aphonia	1/7 (14.3%)		0/32 (0%)		0/31 (0%)
Headache	0/7 (0%)		0/32 (0%)		4/31 (12.9%)
Renal and urinary disorders
Calculus bladder	1/7 (14.3%)		0/32 (0%)		0/31 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.