AcromegalyPhase 4PAPENCT02668172
Pasireotide LAR and Pegvisomant Study in Acromegaly
A Phase 4 study testing Pasireotide LAR 60 mg and Pegvisomant in people with Acromegaly, run by Erasmus Medical Center at 1 site in Netherlands.
Trial summary
The objective of this study is to assess the efficacy of Pasireotide Long Acting Release (LAR) alone and in combination with weekly Pegvisomant (PEGV) in acromegaIy patients previously controlled with combination treatment of long-acting Somatostatin analogs (LA-SSAs) and PEGV. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acromegaly
- What is being tested?
- Pasireotide LAR 60 mg and Pegvisomant
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteNetherlands
- Study dates
- Aug 2015to Jun 2017
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- written informed consent male or female aged ≥ 18 years
- documentation supporting the diagnosis of acromegaly based on elevated GH and/or IGF-I levels due to a pituitary tumor
- the patient is treated with lanreotide Autogel or octreotide LAR and PEGV (twice) weekly for at least 6 months and has a serum IGF-I level within 120 % of the age adjusted normal limits. These patients were previously not controlled by somatostatin analogs alone.
- female of no childbearing potential or male. No childbearing potential is defined as being postmenopausal for at least 1 year, or women with documented infertility (natural or acquired) or using two acceptable contraceptive measures, except for oral contraceptives.
- male subjects must agree that, if their partner is at risk of becoming pregnant, they will use a medically accepted, effective method of contraception (i.e. use a condom) for the duration of the study
- subjects must be willing and able to comply with study restrictions and to remain at the clinic for the required duration during the study period and willing to return to the clinic for the follow up evaluation as specified in the protocol.
Who cannot join
- Patients will not be included in the study if he or she:
- has undergone pituitary surgery or radiotherapy within 6 months prior to study entry.
- it is anticipated that the patient will receive pituitary surgery or radiotherapy during the study.
- has a history of hypersensitivity to lanreotide, octreotide or pegvisomant or drugs with a similar chemical structure
- has been treated with any unlicensed drug within the last 30 days before study entry.
- has abnormal hepatic function at study entry (defined as AST, ALT, gGT, alkaline phosphatase, or total bilirubin above 3 ULN)
Show all 14Show fewer
- is at risk of pregnancy or is lactating. Females of childbearing potential must provide a negative pregnancy test within 5 days before the start of the study and must be using contraception. Non-childbearing potential is defined as post-menopause for at least one year, surgical sterilization or hysterectomy at least three months before the start of the study.
- has a history of, or known current problems with alcohol or drug abuse.
- has a mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude.
- has abnormal baseline findings, any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardize the subject's safety or decrease the chance of obtaining satisfactory data needed to achieve the objective(s) of the study.
- renal insufficiency, clearance < 50ml/min
- poorly controlled diabetes mellitus with an HbA1c > 9.0%
- patients with a QTc > 500 ms on the EKG
- participation in a clinical trial in the last 6 months
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Efficacy and Safety of Pasireotide Long Acting Release (LAR) in Combination With Weekly Pegvisomant in Previously Controlled Acromegaly Patients on Combination Treatment of Long-Acting Somatostatin Analogues and Weekly Pegvisomant
The objective of this study is to assess the efficacy of Pasireotide Long Acting Release (LAR) alone and in combination with weekly Pegvisomant (PEGV) in acromegaIy patients previously controlled with combination treatment of long-acting Somatostatin analogs (LA-SSAs) and PEGV.
Read the detailed description
Pasireotide Long Acting Release (Signifor ®), a novel long-acting multi-receptor ligand somatostatin analogue, has been shown to be more effective for the treatment of GH-secreting pituitary adenomas than currently used long-acting somatostatin analogues (LA-SSAs). The long-term efficacy of acromegaly patients using LA-SSAs in combination with PEGV was over 90% in terms of normalization of IGF-I. The combination of PEGV with pasireotide LAR has not been studied yet. Combining PEGV with pasireotide LAR could result in a lower dose and less injections of pegvisomant. This may ultimately lead to a more cost-effective treatment and improved quality of life.
- Conditions
- Acromegaly
- Being tested
- Pasireotide LAR 60 mg, Pegvisomant
- Keywords
- pegvisomant, pasireotide LAR, long acting somatostatin analogues
- Medical subject headings
- Acromegaly
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pasireotide LAR 60 mgDrug
Also called Signifor, SOM230
as mono-therapy or in combination with pegvisomant
PegvisomantDrug
Also called Somavert
only in combination with pasireotide LAR
| Study group | Role | What they receive |
|---|---|---|
| Pasireotide LAR 60 mg monotherapy week 12 | Experimental | After enrollment, acromegaly patients on combination treatment will half their regular weekly dose of pegvisomant (PEGV) for 12 weeks (run-in period).
When insuline-like growth factor 1 (IGF-I) remains within the age adjusted normal limits after 12 weeks, PEGV and the LA-SSA (Octreotide Long Acting Release (LAR) or Lanreotide Autogel) with Pegvisomant (PEGV) are discontinued and patients are switched to pasireotide LAR 60 mg for 12 weeks. Receives: Drug: Pasireotide LAR 60 mg |
| Pasireotide LAR 60 mg and Pegvisomant week 12 | Experimental | When IGF-I rises above the adjusted normal limits after 12 weeks (run-in period), these subjects will switch their LA-SSA to Pasireotide LAR 60 mg every 4 weeks and continue with the reduced PEGV dose of the run-in period, for the remaining 12 weeks. Receives: Drug: Pasireotide LAR 60 mg; Drug: Pegvisomant |
| Pasireotide LAR 60 mg and Pegvisomant week 24 | Experimental | Between week 12 and 24 dose adaptations of PEGV are not permitted unless IGF-I drops below the age adjusted normal limits, then the dose of PEGV will be decreased stepwise with 20 mg weekly until IGF-I is within the age adjusted normal limits.
At week 24, efficacy will be assessed, as the number of patients with a normal IGF-I in the two different groups; the combination Pasireotide LAR 60 mg / PEG V dose and monotherapy Pasireotide LAR 60 mg.
From week 24 patients will continue with Pasireotide LAR 60 mg monotherapy, or Pasireotide LAR will be combined with 50% of the original dose of PEGV, or with an increasing dose of PEGV every 8 weeks depending on the treatment arm. Receives: Drug: Pasireotide LAR 60 mg; Drug: Pegvisomant |
What is being measured
The primary outcome is the main question the study is designed to answer.
The proportion of patients with normalized IGF1 levels at 24 weeks in the pasireotide LAR monotherapy group and in the pasireotide LAR combined with pegvisomant group
Measured: 24 weeks
Secondary outcomes (10)
The proportion of patients with normalized IGF1 levels after 48 weeks of pasireotide LAR monotherapy
Measured: 48 weeks
The proportion of patients with normalized IGF1 levels after 48 weeks combination treatment of pasireotide LAR with weekly pegvisomant.
Measured: 48 weeks
The necessary dose of pegvisomant during combination treatment of pasireotide LAR with pegvisomant in patients with an IGF-I level within the age adjusted normal limits
Measured: 48 weeks
Change in tumor volume by pituitary MRI
Measured: Baseline and 48 weeks
Tolerability and safety profile of pasireotide Long Acting Release (LAR) monotherapy
Toxicity will be assessed using the National Cancer Institute-Common Toxicology Criteria Adverse Events version 4 (NCI-CTCAE v.4.03) and for laboratory assessments that include biochemistry, hematology, urinalysis; special safety assessments that include the regular monitoring and recording of blood glucose, insulin, HbA1c, GH and IGF-1, thyroid and liver function tests, gallbladder examinations and ECGs. Concomitant medications/Significant nondrug therapies will be assessed from study enrollment until the safety follow-up.
Measured: 48 weeks
Tolerability and safety profile of pasireotide LAR and pegvisomant combination therapy
Toxicity will be assessed using the National Cancer Institute-Common Toxicology Criteria Adverse Events version 4 (NCI-CTCAE v.4.03) and for laboratory assessments that include biochemistry, hematology, urinalysis; special safety assessments that include the regular monitoring and recording of blood glucose, insulin, HbA1c, and IGF-1, thyroid and liver function tests, gallbladder examinations and ECGs. Concomitant medications/Significant nondrug therapies will be assessed from study enrollment until the safety follow-up.
Measured: 48 weeks
Evaluation of long term effect of pasireotide LAR with or without pegvisomant on AcroQol, PASQ and signs and symptoms of acromegaly
AcroQol is quality of life questionnaire specifically designed for acromegaly
Measured: Change in scores as measured by AcroQoL from baseline to week 48
Evaluation of long term effect of pasireotide LAR with or without pegvisomant on AcroQol, PASQ and signs and symptoms of acromegaly
PASQ are questionnaire for the disease specific symptoms
Measured: Change in scores as measured by PASQ from baseline to week 48
Evaluation of long term effect of pasireotide LAR with or without pegvisomant on AcroQol, PASQ and signs and symptoms of acromegaly
Measured: Description of signs and symptoms of acromegaly
Evaluation of body composition by Dual-energy X-ray Absorptiometry (DEXA) scan
Measured: baseline and 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2016 (estimated)
- Study startAug 2015
- Primary completionMar 2017 (estimated)
- Study completionJun 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AcromegalyStudies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Principal investigator, s neggers, Erasmus Medical Center
- Investigators
- Sebastian Neggers, MD PhD, Principal investigator, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02668172
- Sponsor's protocol ID
- NL49517.078.14
- Other IDs
- 2014-002219-41, NTR5282, 2014
- Acronym
- PAPE
- Status last verified
- Aug 2016
- First submitted
- 7 Dec 2015
- Last updated
- 3 Aug 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Muhammad A, van der Lely AJ, Delhanty PJD, Dallenga AHG, Haitsma IK, Janssen JAMJL, Neggers SJCMM. Efficacy and Safety of Switching to Pasireotide in Patients With Acromegaly Controlled With Pegvisomant and First-Generation Somatostatin Analogues (PAPE Study). J Clin Endocrinol Metab. 2018 Feb 1;103(2):586-595. doi: 10.1210/jc.2017-02017.
PubMed 29155991
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Pasireotide Long Acting Release (LAR) in Combination With Weekly Pegvisomant in Previously Controlled Acromegaly Patients on Combination Treatment of Long-Acting Somatostatin Analogues and Weekly Pegvisomant
- ClinicalTrials.gov ID
- NCT02668172
- Acronym / sponsor ID
- PAPE / NL49517.078.14
- Conditions
- Acromegaly
- Keywords
- pegvisomant, pasireotide LAR, long acting somatostatin analogues
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Aug 2015
- Primary completion
- Mar 2017 (estimated)
- Study completion
- Jun 2017 (estimated)
- First posted
- 29 Jan 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this study is to assess the efficacy of Pasireotide Long Acting Release (LAR) alone and in combination with weekly Pegvisomant (PEGV) in acromegaIy patients previously controlled with combination treatment of long-acting Somatostatin analogs (LA-SSAs) and PEGV.
Detailed description
Pasireotide Long Acting Release (Signifor ®), a novel long-acting multi-receptor ligand somatostatin analogue, has been shown to be more effective for the treatment of GH-secreting pituitary adenomas than currently used long-acting somatostatin analogues (LA-SSAs). The long-term efficacy of acromegaly patients using LA-SSAs in combination with PEGV was over 90% in terms of normalization of IGF-I. The combination of PEGV with pasireotide LAR has not been studied yet. Combining PEGV with pasireotide LAR could result in a lower dose and less injections of pegvisomant. This may ultimately lead to a more cost-effective treatment and improved quality of life.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Pasireotide LAR 60 mg monotherapy week 12 | Experimental | Drug: Pasireotide LAR 60 mgAfter enrollment, acromegaly patients on combination treatment will half their regular weekly dose of pegvisomant (PEGV) for 12 weeks (run-in period). When insuline-like growth factor 1 (IGF-I) remains within the age adjusted normal limits after 12 weeks, PEGV and the LA-SSA (Octreotide Long Acting Release (LAR) or Lanreotide Autogel) with Pegvisomant (PEGV) are discontinued and patients are switched to pasireotide LAR 60 mg for 12 weeks. |
| Pasireotide LAR 60 mg and Pegvisomant week 12 | Experimental | Drug: Pasireotide LAR 60 mg, Drug: PegvisomantWhen IGF-I rises above the adjusted normal limits after 12 weeks (run-in period), these subjects will switch their LA-SSA to Pasireotide LAR 60 mg every 4 weeks and continue with the reduced PEGV dose of the run-in period, for the remaining 12 weeks. |
| Pasireotide LAR 60 mg and Pegvisomant week 24 | Experimental | Drug: Pasireotide LAR 60 mg, Drug: PegvisomantBetween week 12 and 24 dose adaptations of PEGV are not permitted unless IGF-I drops below the age adjusted normal limits, then the dose of PEGV will be decreased stepwise with 20 mg weekly until IGF-I is within the age adjusted normal limits. At week 24, efficacy will be assessed, as the number of patients with a normal IGF-I in the two different groups; the combination Pasireotide LAR 60 mg / PEG V dose and monotherapy Pasireotide LAR 60 mg. From week 24 patients will continue with Pasireotide LAR 60 mg monotherapy, or Pasireotide LAR will be combined with 50% of the original dose of PEGV, or with an increasing dose of PEGV every 8 weeks depending on the treatment arm. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- written informed consent male or female aged ≥ 18 years
- documentation supporting the diagnosis of acromegaly based on elevated GH and/or IGF-I levels due to a pituitary tumor
- the patient is treated with lanreotide Autogel or octreotide LAR and PEGV (twice) weekly for at least 6 months and has a serum IGF-I level within 120 % of the age adjusted normal limits. These patients were previously not controlled by somatostatin analogs alone.
- female of no childbearing potential or male. No childbearing potential is defined as being postmenopausal for at least 1 year, or women with documented infertility (natural or acquired) or using two acceptable contraceptive measures, except for oral contraceptives.
- male subjects must agree that, if their partner is at risk of becoming pregnant, they will use a medically accepted, effective method of contraception (i.e. use a condom) for the duration of the study
Key exclusion criteria (14 listed)
- has undergone pituitary surgery or radiotherapy within 6 months prior to study entry.
- it is anticipated that the patient will receive pituitary surgery or radiotherapy during the study.
- has a history of hypersensitivity to lanreotide, octreotide or pegvisomant or drugs with a similar chemical structure
- has been treated with any unlicensed drug within the last 30 days before study entry.
- has abnormal hepatic function at study entry (defined as AST, ALT, gGT, alkaline phosphatase, or total bilirubin above 3 ULN)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pasireotide LAR 60 mgAlso: Signifor, SOM230as mono-therapy or in combination with pegvisomant | Drug | Pasireotide LAR 60 mg and Pegvisomant week 12, Pasireotide LAR 60 mg and Pegvisomant week 24, Pasireotide LAR 60 mg monotherapy week 12 |
| PegvisomantAlso: Somavertonly in combination with pasireotide LAR | Drug | Pasireotide LAR 60 mg and Pegvisomant week 12, Pasireotide LAR 60 mg and Pegvisomant week 24 |
Primary outcome
The proportion of patients with normalized IGF1 levels at 24 weeks in the pasireotide LAR monotherapy group and in the pasireotide LAR combined with pegvisomant group
Time frame: 24 weeks
10 secondary outcomes
The proportion of patients with normalized IGF1 levels after 48 weeks of pasireotide LAR monotherapy
Time frame: 48 weeks
The proportion of patients with normalized IGF1 levels after 48 weeks combination treatment of pasireotide LAR with weekly pegvisomant.
Time frame: 48 weeks
The necessary dose of pegvisomant during combination treatment of pasireotide LAR with pegvisomant in patients with an IGF-I level within the age adjusted normal limits
Time frame: 48 weeks
Change in tumor volume by pituitary MRI
Time frame: Baseline and 48 weeks
Tolerability and safety profile of pasireotide Long Acting Release (LAR) monotherapy
Time frame: 48 weeks
Tolerability and safety profile of pasireotide LAR and pegvisomant combination therapy
Time frame: 48 weeks
Evaluation of long term effect of pasireotide LAR with or without pegvisomant on AcroQol, PASQ and signs and symptoms of acromegaly
Time frame: Change in scores as measured by AcroQoL from baseline to week 48
Evaluation of long term effect of pasireotide LAR with or without pegvisomant on AcroQol, PASQ and signs and symptoms of acromegaly
Time frame: Change in scores as measured by PASQ from baseline to week 48
Evaluation of long term effect of pasireotide LAR with or without pegvisomant on AcroQol, PASQ and signs and symptoms of acromegaly
Time frame: Description of signs and symptoms of acromegaly
Evaluation of body composition by Dual-energy X-ray Absorptiometry (DEXA) scan
Time frame: baseline and 48 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2016.
- Derived from this study: PubMed 29155991Muhammad A, van der Lely AJ, Delhanty PJD, Dallenga AHG, Haitsma IK, Janssen JAMJL, Neggers SJCMM. Efficacy and Safety of Switching to Pasireotide in Patients With Acromegaly Controlled With Pegvisomant and First-Generation Somatostatin Analogues (PAPE Study). J Clin Endocrinol Metab. 2018 Feb 1;103(2):586-595. doi: 10.1210/jc.2017-02017.
- Summary of study at the WHO International Clinical Trials Registry PlatformLink provided by the sponsor.
Related trials for Acromegaly
RecruitingObservational study
An Observational Study of Octreotide Subcutaneous Depot in Patients With Acromegaly
Acromegaly
RecruitingPhase 3
A Study to Assess the Efficacy and Safety of Debio 4126 in Participants With Acromegaly Previously Treated With Somatostatin Analogs
Acromegaly
RecruitingObservational study
An Investigation of Pituitary Tumors and Related Hypothalmic Disorders
Panhypopituitarism, Gigantism/Acromegaly
Recruiting
Managing Pasireotide-associated Hyperglycaemia in Acromegaly With Ketogenic Diet
Acromegaly Due to Pituitary Adenoma, Hyperglycemia
Not yet recruitingPhase 3
PRESTO: A Phase III Randomised Controlled Trial of Dose-escalated Proton Beam Therapy Versus Standard of Care Radiotherapy for Functioning Pituitary Tumours
Acromegaly Due to Pituitary Adenoma, Cushing's Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sebastian Neggers, MD PhD principal investigator
Erasmus Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Pasireotide LAR 60 mg and Pegvisomant in people with Acromegaly, run by Erasmus Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The proportion of patients with normalized IGF1 levels at 24 weeks in the pasireotide LAR monotherapy group and in the pasireotide LAR combined with pegvisomant group (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02668172, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2016.