A multicenter, single arm, proof of concept study to investigate in a first stage the efficacy of a combination therapy of Sandostatin® LAR® and Cabergoline, optionally followed by a combination of Sandostatin® LAR® and pegvisomant, in acromegalic patients only partially responsive to somatostatin analog monotherapy - PHOENIX

• Register: EUCTR
• Last refreshed on: 10 December 2012
• Main ID: EUCTR2005-002919-24-DE
• Date of registration: 20/06/2006
• Prospective Registration: No
• Primary sponsor: Novartis Pharma GmbH
• Public title: A multicenter, single arm, proof of concept study to investigate in a first stage the efficacy of a combination therapy of Sandostatin® LAR® and Cabergoline, optionally followed by a combination of Sandostatin® LAR® and pegvisomant, in acromegalic patients only partially responsive to somatostatin analog monotherapy - PHOENIX
• Scientific title: A multicenter, single arm, proof of concept study to investigate in a first stage the efficacy of a combination therapy of Sandostatin® LAR® and Cabergoline, optionally followed by a combination of Sandostatin® LAR® and pegvisomant, in acromegalic patients only partially responsive to somatostatin analog monotherapy - PHOENIX
• Date of first enrolment: 09/02/2006
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-002919-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Germany

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female patients aged 18 years or older.
2. Patients with prior surgery of micro- or macroadenoma of the pituitary.
3. At least 6 months chronic treatment with somatostatin analogues abd the last 3 months treated with the highest dose of somatostatin analogues.

5. Lack of suppression of GH nadir to < 1.0 mcg/l, after oral administration of 75 g of glucose (OGTT) and IGF-I levels at least 10% above the normal value ± 2 SD must be proven within 4 weeks prior to visit 1.
However, if acromegaly symptoms are inadequately controlled as defined in the acromegaly comorbidities and symptom evaluation (as judged by the investigator), an abnormal GH or IGF-1-value as defined above is sufficient.
6. Patient’s written informed consent.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Requires surgery for recent significant deterioration in visual fields or other neurological signs, which are related to the pituitary tumor mass.
2. Radiotherapy planned or radiotherapy for acromegaly within the last 2 years.
3. Symptomatic cholelithiasis that is clinically relevant.
4. Psychose in anamnesis.
5. Severe cardiovascular dysfunction (for example cardiomyopathy, congestive heart failure NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, ventricular fibrillation, fibrosis of heart valvila and lung.
6. Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis, or persistent ALT, AST, alkaline phosphatase 2 x > upper limit of normal, or total bilirubin 1.5 x > upper limit of normal.
7. Any medical conditions contraindicated in the SPC of all study drugs.
8. Abnormal clinical laboratory values considered by the Investigator to be clinically significant and which could affect the interpretation of the study results.
9. 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.
10. Patients with a complete resistence to somatostatin analogues therapy.
11. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/ml).
12. Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >40 mIU/m or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy or are using one or more of the following acceptable methods of contraception: surgical sterilization (e.g., bilateral tubal ligation, vasectomy), hormonal contraception (implantable, patch, oral), and double-barrier methods (any double combination of: IUD, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Reliable contraception should be maintained throughout the study and for 30 days after study drug discontinuation.
13. Receiving treatment with dopamine agonists within the last 6 months.
14. Prior treatment with GH-receptor-antagonists.
15. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half lives of enrollment, whichever is longer.
16. History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures.
17. History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin.
18. Unable to complete the entire study for any reason.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

acromegaly
MedDRA version: M15 Level: LLT Classification code 10000599

Intervention(s)

Trade Name: Sandostatin LAR Monatsdepot 20 mg
Product Name: Sandostatin LAR-Monatsdepot
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Octreotid
Current Sponsor code: SMS995
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Trade Name: Sandostatin LAR-Monatsdepot
Product Name: Sandostatin LAR-Monatsdepot
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Octreotid
Current Sponsor code: SMS995
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-

Trade Name: Dostinex 0,5 mg Tabletten
Product Name: Dostinex
Pharmaceutical Form: Tablet
INN or Proposed INN: Cabergolin
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-

Trade Name: Somavert
Product Name: Somavert
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Pegvisomant
CAS Number: 218620-50-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Trade Name: Somavert
Product Name: Somavert
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Pegvisomant
CAS Number: 218620-50-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-

Trade Name: Somavert
Product Name: Somavert
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Pegvisomant
CAS Number: 218620-50-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Main Objective: The primary objective of this study is to demonstrate the ability of a combination therapy with Sandostatin LAR and Cabergoline to reduce GH and IGF-I levels in acromegalic patients that are only partially responsive to Sandostatin LAR monotherapy. For the patients not responding to the combination after 5 months, a switch to the combination Sandostatin LAR and pegvisomant will be foreseen for a further 3 months therapy.

Secondary Objective: #the ability of a combination therapy with Sandostatin LAR and Cabergoline to reduce GH and IGF-I levels in acromegalic patients that are only partially responsive to Sandostatin LAR monotherapy
#the ability of a combination therapy with Sandostatin LAR and pegvisomant to reduce IGF-I levels by 25% (or to normalize IGF-I levels) in acromegalic patients that are only partially responsive to Sandostatin LAR and cabergoline
#the ability of a combination therapy with Sandostatin LAR and Cabergoline to normalize GH and/or IGF-I levels in acromegalic patients that are only partially responsive to Sandostatin LAR monotherapy
#safety and tolerability as well as the effect of the combination therapy with Sandostatin LAR and Cabergoline optionally followed by Sandostatin LAR and pegvisomant on tumor size, quality of life and to relieve clinical symptoms.

Primary end point(s): Reduction or normalization of GH and IGF-I levels in acromegalic patients only partially responding to Sandostatin LAR monotherapy after surgery.

Response is defined as a decrease in GH and IGF-1 of at least 25% compared to study baseline values or normalization in these parameters to age- and sex-adjusted levels according to Brabant after 8 months of treatment with 30mg Sandostatin LAR and Cabergoline.

Secondary ID(s)

CSMS995BDE16