Acromegaly, Cushing's Disease, Dumping Syndrome, Ectopic ACTH Secreting (EAS) Tumors, Melanoma Negative for bRAF, Melanoma Negative for nRAS, Neuroendocrine Tumors, Pituitary Tumors, Prostate Cancer
Conditions
Keywords
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
Brief summary
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
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.
Interventions
DRUGPasireotide
Administered subcutaneously in strengths 0.3mg, 0.6mg and 0.9mg. Doses to be taken BID or TID, dependent on parent study guidelines.
DRUGCabergoline
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.
DRUGPasireotide LAR
Long Acting Release is administered by a single intramuscular (i.m.) monthly injection. The strengths are 10mg, 20mg, 40mg and 60mg. All doses to be taken q28days. Strength is dependent on parent study guidelines.
Sponsors
RECORDATI GROUP
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 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. 2. Patient is currently benefiting from the treatment with pasireotide, as determined by the investigator 3. Patient has demonstrated compliance, as assessed by the investigator, with the parent study requirements. 4. Willingness and ability to comply with scheduled visits, treatment plans and any other study procedures. 5. 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
1. 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. 2. 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. 3. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events to Evaluate Long Term Safety Data | Baseline up to approximately 10 years | Collect long term safety data, i.e. SAEs and AEs. SAES will be reviewed and reported as part of the regular pharmacovigilance activities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Clinical Benefit as Assessed by the Investigator | Baseline up to approximately 10 years | Efficacy was assessed by the investigator at each scheduled visit using a binary (yes/no) response confirming the investigator's judgement of clinical benefit (via the question: Does investigator confirm that the subject continues to have clinical benefit from the study treatment). No other measures of efficacy were used in this study. |
Countries
Argentina, Belgium, Brazil, Bulgaria, Canada, France, Germany, Greece, Hungary, India, Israel, Italy, Japan, Malaysia, Mexico, Netherlands, Peru, Poland, Portugal, Romania, Russia, South Korea, Spain, Switzerland, Taiwan, Thailand, Turkey (Türkiye), United States
Participant flow
Recruitment details
No target number of patients pre-specified for this study
Participants by arm
| Arm | Count |
|---|---|
| All Subjects Patients who were treated with and had benefitted from pasireotide in the parent studies remained enrolled in this study and were elegible for the analysis | 337 |
| Total | 337 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Post-treatment Follow-up | administrative problem | 5 |
| Post-treatment Follow-up | Adverse Event | 8 |
| Post-treatment Follow-up | Lack of Efficacy | 14 |
| Post-treatment Follow-up | Lost to Follow-up | 3 |
| Post-treatment Follow-up | Protocol Violation | 3 |
| Post-treatment Follow-up | Withdrawal by Subject | 6 |
| Treatment Period | administrative problem | 3 |
| Treatment Period | Adverse Event | 17 |
| Treatment Period | Death | 6 |
| Treatment Period | Lack of Efficacy | 22 |
| Treatment Period | Lost to Follow-up | 7 |
| Treatment Period | Physician Decision | 14 |
| Treatment Period | Protocol Violation | 5 |
| Treatment Period | Withdrawal by Subject | 24 |
Baseline characteristics
| Characteristic | All Subjects | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 32 Participants | — |
| Age, Categorical Between 18 and 65 years | 305 Participants | — |
| Age, Continuous | 47.6 years STANDARD_DEVIATION 12.43 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 190 Participants | — |
| Sex: Female, Male Male | 147 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 8 / 337 |
| other Total, other adverse events | 220 / 337 |
| serious Total, serious adverse events | 91 / 337 |
Outcome results
Primary
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.
Time frame: Baseline up to approximately 10 years
Population: The Safety Set included all patients who received at least one dose of study medication (pasireotide) after enrolling into the roll-over protocol
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Subjects | Incidence of Adverse Events to Evaluate Long Term Safety Data | AEs : All grades | 265 participants |
| All Subjects | Incidence of Adverse Events to Evaluate Long Term Safety Data | AEs : Grades ≥3 | 102 participants |
| All Subjects | Incidence of Adverse Events to Evaluate Long Term Safety Data | Treatment-related AEs : All grades | 127 participants |
| All Subjects | Incidence of Adverse Events to Evaluate Long Term Safety Data | Treatment-related AEs : Grades ≥3 | 39 participants |
| All Subjects | Incidence of Adverse Events to Evaluate Long Term Safety Data | SAEs : All grades | 91 participants |
| All Subjects | Incidence of Adverse Events to Evaluate Long Term Safety Data | SAEs : Grades ≥3 | 72 participants |
| All Subjects | Incidence of Adverse Events to Evaluate Long Term Safety Data | Fatal SAEs : All grades | 8 participants |
| All Subjects | Incidence of Adverse Events to Evaluate Long Term Safety Data | Fatal SAEs : Grades ≥3 | 8 participants |
| All Subjects | Incidence of Adverse Events to Evaluate Long Term Safety Data | Treatment-related fatal SAEs : All grades | 0 participants |
| All Subjects | Incidence of Adverse Events to Evaluate Long Term Safety Data | Treatment-related fatal SAEs : Grades ≥3 | 0 participants |
| All Subjects | Incidence of Adverse Events to Evaluate Long Term Safety Data | AEs leading to discontinuation : All grades | 20 participants |
| All Subjects | Incidence of Adverse Events to Evaluate Long Term Safety Data | AEs leading to discontinuation : Grades ≥3 | 11 participants |
| All Subjects | Incidence of Adverse Events to Evaluate Long Term Safety Data | Treatment-related AEs leading to discontinuation : All grades | 16 participants |
| All Subjects | Incidence of Adverse Events to Evaluate Long Term Safety Data | Treatment-related AEs leading to discontinuation : Grades ≥3 | 7 participants |
| All Subjects | Incidence of Adverse Events to Evaluate Long Term Safety Data | AEs leading to dose adjustment/interruption : All grades | 39 participants |
| All Subjects | Incidence of Adverse Events to Evaluate Long Term Safety Data | AEs leading to dose adjustment/interruption : Grades ≥3 | 13 participants |
| All Subjects | Incidence of Adverse Events to Evaluate Long Term Safety Data | AEs requiring additional therapy : All grades | 220 participants |
| All Subjects | Incidence of Adverse Events to Evaluate Long Term Safety Data | AEs requiring additional therapy : Grades ≥3 | 62 participants |
Secondary
Percentage of Patients With Clinical Benefit as Assessed by the Investigator
Efficacy was assessed by the investigator at each scheduled visit using a binary (yes/no) response confirming the investigator's judgement of clinical benefit (via the question: Does investigator confirm that the subject continues to have clinical benefit from the study treatment). No other measures of efficacy were used in this study.
Time frame: Baseline up to approximately 10 years
Population: Number of patients judged by the investigator to be clinically benefitting from treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Subjects | Percentage of Patients With Clinical Benefit as Assessed by the Investigator | Month 12 | 21 Participants |
| All Subjects | Percentage of Patients With Clinical Benefit as Assessed by the Investigator | Month 60 | 12 Participants |
| All Subjects | Percentage of Patients With Clinical Benefit as Assessed by the Investigator | Month 24 | 17 Participants |
| All Subjects | Percentage of Patients With Clinical Benefit as Assessed by the Investigator | Month 72 | 12 Participants |
| All Subjects | Percentage of Patients With Clinical Benefit as Assessed by the Investigator | Month 6 | 28 Participants |
| All Subjects | Percentage of Patients With Clinical Benefit as Assessed by the Investigator | Month 84 | 8 Participants |
| All Subjects | Percentage of Patients With Clinical Benefit as Assessed by the Investigator | Month 36 | 14 Participants |
| All Subjects | Percentage of Patients With Clinical Benefit as Assessed by the Investigator | Month 96 | 5 Participants |
| All Subjects | Percentage of Patients With Clinical Benefit as Assessed by the Investigator | Month 18 | 19 Participants |
| All Subjects | Percentage of Patients With Clinical Benefit as Assessed by the Investigator | Month 108 | 5 Participants |
| All Subjects | Percentage of Patients With Clinical Benefit as Assessed by the Investigator | Month 48 | 15 Participants |
| All Subjects | Percentage of Patients With Clinical Benefit as Assessed by the Investigator | Month 120 | 2 Participants |
| All Subjects | Percentage of Patients With Clinical Benefit as Assessed by the Investigator | Month 3 | 29 Participants |
| Pasireotide Long Acting Release (LAR) | Percentage of Patients With Clinical Benefit as Assessed by the Investigator | Month 120 | 0 Participants |
| Pasireotide Long Acting Release (LAR) | Percentage of Patients With Clinical Benefit as Assessed by the Investigator | Month 3 | 256 Participants |
| Pasireotide Long Acting Release (LAR) | Percentage of Patients With Clinical Benefit as Assessed by the Investigator | Month 6 | 250 Participants |
| Pasireotide Long Acting Release (LAR) | Percentage of Patients With Clinical Benefit as Assessed by the Investigator | Month 12 | 234 Participants |
| Pasireotide Long Acting Release (LAR) | Percentage of Patients With Clinical Benefit as Assessed by the Investigator | Month 18 | 216 Participants |
| Pasireotide Long Acting Release (LAR) | Percentage of Patients With Clinical Benefit as Assessed by the Investigator | Month 24 | 198 Participants |
| Pasireotide Long Acting Release (LAR) | Percentage of Patients With Clinical Benefit as Assessed by the Investigator | Month 36 | 177 Participants |
| Pasireotide Long Acting Release (LAR) | Percentage of Patients With Clinical Benefit as Assessed by the Investigator | Month 48 | 162 Participants |
| Pasireotide Long Acting Release (LAR) | Percentage of Patients With Clinical Benefit as Assessed by the Investigator | Month 60 | 140 Participants |
| Pasireotide Long Acting Release (LAR) | Percentage of Patients With Clinical Benefit as Assessed by the Investigator | Month 72 | 98 Participants |
| Pasireotide Long Acting Release (LAR) | Percentage of Patients With Clinical Benefit as Assessed by the Investigator | Month 84 | 21 Participants |
| Pasireotide Long Acting Release (LAR) | Percentage of Patients With Clinical Benefit as Assessed by the Investigator | Month 96 | 1 Participants |
| Pasireotide Long Acting Release (LAR) | Percentage of Patients With Clinical Benefit as Assessed by the Investigator | Month 108 | 1 Participants |