Acromegaly OOC-ACM-302

Principal Investigator: Debra Simmons
Keywords: Acromegaly , Somatostatin , Octreotide Department: Endocrinology/Diabetes Researc
IRB Number: 00087273 Co Investigator:  
Specialty: Cardiology, Radiology
Sub Specialties: Magnetic Resonance Imaging – MRI
Recruitment Status: Recruiting

Contact Information

Julianna Dorsch
Julianna.Dorsch@hsc.utah.edu
801-587-5200

Brief Summary

A phase 3, randomized, open-label, active controlled, multicenter study to evaluate maintenance of response, safety and patient reported outcomes in acromegaly patients treated with octreotide capsules, and in patients treated with standard of care parenteral somatostatin receptor ligands who previously tolerated and demonstrated a biochemical control on both treatments.

STUDY OBJECTIVES

  • To assess maintenance of biochemical control of octreotide capsules compared to parenteral SRLs in patients with acromegaly, who previously demonstrated biochemical control on both treatments.
  • To assess symptomatic response to octreotide capsules compared to parenteral SRLs.
  • To assess patient reported outcome (PRO) in patients treated with octreotide capsules compared to parenteral SRLs.
  • To evaluate the safety profile of octreotide capsules compared to parenteral SRLs.

Combination phase sub-study objective

  • To assess the efficacy of octreotide capsules co-administered with cabergoline in the treatment of acromegaly patients with modestly elevated IGF-1 levels (Defined as 1.3≤IGF-1 <2 ULN).

 

Inclusion Criteria

 
 
1. Adult subjects, aged 18 to 75 years old, inclusive, at the Screening visit.
 
2. Patients with acromegaly, defined as documented evidence of GH-secreting pituitary tumor that is abnormally responsive to an oral glucose tolerance test or abnormal IGF-1 levels (>1 x  ULN), any time in the past, who are currently receiving parenteral SRLs (octreotide or lanreotide but not pasireotide) for at least 6 months with a stable dose for at least the last four months.
 
3. Documented biochemical control of their acromegaly on the current dose of SRL (IGF-1 x 1.3  ULN and mean integrated GH less than 2.5 ng/mL over two hours), based on Screening assessment.
 
4. Patients able and willing to comply with the requirements of the protocol at the time of Screening.
 
5. Women who are of childbearing potential should use an acceptable method for birth control. Acceptable methods include hormonal contraception (oral contraceptives, patch, implant, and injection), intrauterine devices, or double barrier methods (e.g., vaginal diaphragm, vaginal sponge plus condom or condom plus spermicidal jelly), sexual abstinence or a vasectomized partner. Women may be surgically sterile or at least 1 year post-last menstrual period. Women taking oral contraception containing levonorgestrel should either change treatment (at least one month prior to first study medication dose) or use a mechanical barrier method.
 
6. Patients able to understand and sign written informed consent to participate in the study.

Exclusion Criteria

 
1. Patients taking injections of long-acting SRLs less frequently than once every eight weeks (dosing interval > 8 weeks).
 
2. Patients who previously participated in CH-ACM-01.
 
3. Symptomatic cholelithiasis.
 
4. Received pituitary radiotherapy within five years prior to screening (including total body, head and neck or stereotactic radiotherapy).
 
5. Undergone pituitary surgery within six months prior to screening or have elected surgery planned within the course of the core study.
 
6. High-risk pattern* of pituitary tumor location on pituitary MRI/Computed tomography (CT) as per medical history or most recent MRI.
 
7. History of unstable angina or acute myocardial infarction within the 12 weeks preceding the screening visit or other clinically significant cardiac disease at the time of screening as judged by the Principal Investigator.
 
8. Any clinically significant uncontrolled nervous system, gastrointestinal (GI), renal, pulmonary, or hepatic concomitant disease that in the Investigator’s opinion would preclude patient participation.
 
9. Evidence of active malignant disease or malignancies diagnosed within the previous 1 year (except for basal cell carcinoma and uncomplicated --up to stage 1 squamous cell carcinoma that has been
excised and cured).
 
10. Known allergy or hypersensitivity to any of the test compounds or materials.
 
11. Known uncontrolled diabetes defined as having a fasting glucose  150 mg/dL (8.3 mmol/L) or glycosylated hemoglobin (HbA1c)  8% (patients can be rescreened after diabetes is brought under adequate control, or in case HbA1c < 8%).
 
12. Known defects in visual fields due to optic chiasmal compression or other neurological signs, related to the pituitary tumor mass. Patients with long-standing (>12 months), fixed, minor defects may be considered on a case-by-case basis after consultation with the medical monitor.
 
13. Female patients who are pregnant or lactating or intending to become pregnant during the study.
 
14. Known history of immunodeficiency (e.g., HIV positive)
 
15. ALT, AST, ALP or GGT > 3  ULN or Total Bilirubin>1.5  ULN.
 
16. Undergone major surgery/surgical therapy for any cause within four weeks prior to enrollment or planned procedure during the study.
 
17. Known hypothyroidism or hypocortisolism not adequately treated with a stable dose of thyroid or steroid hormone replacement therapy for  12 weeks.
 
18. Any condition that may jeopardize study participation (e.g., clinically significant abnormal screening clinical or laboratory finding during screening), the interpretation of study results or may
impede the ability to obtain informed consent (e.g., mental condition).
 
19. History of illicit drug or alcohol abuse within five years.
 
20. Intake of an investigational drug within 30 days prior to initiation of study treatment.
 
21. Treatment with pegvisomant within 12 weeks before the screening visit.
 
22. Treatment with dopamine agonists within 6 weeks before the screening visit.

23. Treatment with pasireotide within 12 weeks before the screening visit.

 

 

*High risk tumor burden is defined by the presence of any of the following:
 Tumor recurrence or growth of residual tumor within one year after surgery or radiation (with the exception of tumor regrowth occurring if SRLs have been stopped in the past)
 Tumor compression of the optic chiasm and invasion of adjacent brain structures (with the exception of sphenoid sinus and cavernous sinus)
 Anticipated need for surgery or radiation during the course of the study period based on tumor growth on serial MRIs
 Metastatic pituitary carcinoma or prior chemotherapy for pituitary carcinoma