Study to Allow Access to Pasireotide for Patients Benefiting From Pasireotide Treatment in Novartis-sponsored Studies

Study Overview
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Brief Summary
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The purpose of this study is to allow continued use of pasireotide in patients who are on pasireotide treatment in a Novartis-sponsored study and are benefiting from the treatment as judged by the investigator.

Detailed Description
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This is a multi-center, open label, phase IV study to provide continued supply of pasireotide to patients being treated in a current Novartis-sponsored study and who are benefiting from treatment with pasireotide alone or in combination with another treatment for Cushing's Disease and Acromegaly . Eligible patients are to be consented and can then continue treatment with pasireotide alone or in combination with another treatment for Cushing's Disease and Acromegaly in this protocol. All patients at their scheduled visits will have drug dispensing information and reported adverse events and serious adverse events collected. A patient will reach the end of study when pasireotide treatment is permanently discontinued and the end of treatment visit has been performed. All patients must be followed up for safety evaluations for 3 months following the last dose of pasireotide LAR treatment and for 1 month following the last dose of pasireotide s.c. treatment. The study is expected to remain open for approximately 10 years or until such time that enrolled patients no longer need treatment with pasireotide or are able to obtain commercial supply according to local regulations for their medical condition.

Official Title
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An Open Label, Multi-center Pasireotide Roll-over Protocol for Patients Who Have Completed a Previous Novartis-sponsored Pasireotide Study and Are Judged by the Investigator to Benefit From Continued Pasireotide Treatment

Conditions
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Cushing's Disease, Acromegaly, Neuroendocrine Tumors, Pituitary Tumors, Ectopic ACTH Secreting (EAS) Tumors, Dumping Syndrome, Prostate Cancer, Melanoma Negative for bRAF, Melanoma Negative for nRAS

Intervention / Treatment
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* Drug: Pasireotide
* Drug: Cabergoline
* Drug: Pasireotide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is currently participating in a Novartis-sponsored study receiving pasireotide (LAR and/or s.c.) on monotherapy or combination therapy (for Cushing's Disease or Acromegaly), and has fulfilled all required assessments in the parent study and patients that are benefiting from the study treatment have no other alternatives. Patient is currently benefiting from the treatment with pasireotide, as determined by the investigator Patient has demonstrated compliance, as assessed by the investigator, with the parent study requirements. Willingness and ability to comply with scheduled visits, treatment plans and any other study procedures. Written informed consent obtained prior to enrolling in roll-over study and receiving study medication. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness. Exclusion Criteria: Patient has been permanently discontinued from pasireotide study treatment in the parent study due to unacceptable toxicity, non-compliance to study procedures, withdrawal of consent or any other reason. 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. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during the study treatment and for 30 days after the final dose of pasireotide s.c. and 84 days after the final dose of pasireotide LAR. Highly effective contraception is defined as either: Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment. Male sterilization (at least 6 months prior to enrolling). For female patients on the study the vasectomized male partner should be the sole partner for that patient. Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (i.e. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child-bearing potential. Sexually active males, unless they use a condom during intercourse while taking drug and for 1 months after pasireotide s.c. last dose and 3 months after pasireotide LAR last dose, should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pasireotide subcutaneous<br>0.3mg, 0.6mg and 0.9mg. Doses to be taken BID or TID, dependent on parent study guidelines. Cabergoline may be combined in this arm for Cushing's Disease and Acromegaly patients. | Drug: Pasireotide<br>* Administered subcutaneously in strengths 0.3mg, 0.6mg and 0.9mg. Doses to be taken BID or TID, dependent on parent study guidelines.<br>* Other names: SOM230; Signifor;Drug: Cabergoline<br>* Cabergoline tablet 0.5mg or 1.0mg taken by mouth once daily may be combined with subcutaneous formulation of pasireotide for Cushing's Disease or Acromegaly. Dose is dependent on parent study guidelines.<br>* Other names: dostinex;|
| Experimental: Pasireotide Long Acting Release (LAR)<br>10mg, 20mg, 40mg and 60mg. All doses to be taken q28days. Strength is dependent on parent study guidelines. | Drug: Pasireotide<br>* Long Acting Release is administered by monthly injection. The strengths are 10mg, 20mg, 40mg and 60mg. All doses to be taken q28days. Strength is dependent on parent study guidelines.<br>* Other names: SOM230; Signifor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events to evaluate long term safety data | Collect long term safety data, i.e. SAEs and AEs. SAES will be reviewed and reported as part of the regular pharmacovigilance activities. | Baseline up to approximately 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with clinical benefit as assessed by the investigator | Clinical benefit rate as defined by Investigator based on the patients 24 hour Urinary Free Cortisol results. | Baseline up to approximately 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SOM230,, roll-over study, pasireotide LAR, Cushing's disease, Acromegaly, neuroendocrine tumorsNETs, pituitary tumors, Ectopic ACTH secreting, EAS, Dumping Syndrome, metastatic prostate cancer, metastatic melanoma, bRAF, nRAS