- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01646684
Phase 1 Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of Pasireotide LAR in Patients With Castration Resistant Prostate Cancer
Phase 1 Study to Evaluate Safety, and Preliminary Efficacy of Pasireotide LAR in Castration Resistant Prostate Cancer
After failure of initial ADT, addition of an anti-androgen is established to treat castration resistant prostate cancer (CRPC). Substitution of the first anti-androgen and anti-androgen withdrawal results in treatment responses in 25-40% of patients for 4-6 months. A more effective second line treatment after failure of first ADT could prolong the time until the state of symptomatic HRPC, which is currently treated with docetaxel and accompanied by significant side effects. Since the importance of the IGF-signaling in PC is not only indicated by preclinical results but also by clinical efficacy of somatostatin analogs, further clinical research with the new somatostatin analog pasireotide is warranted.
This study is designed to define the maximum tolerated dose (MTD) of pasireotide LAR in patients with castration resistant prostate cancer (CRPC). It also aims for a preliminary efficacy evaluation of pasireotide within the dose expansion part at the MTD. Preliminary efficacy will be assessed by evaluation of different measures of prostate cancer e.g. changes in PSA, disease control rate (RECIST 1.1), symptoms and changes of biomarkers linked to the mode of action of pasireotide LAR. The study will also explore characteristics of patients who might benefit most from this treatment approach
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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-
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Berlin, Germany, 10117
- Novartis Investigative Site
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Dresden, Germany, 01307
- Novartis Investigative Site
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Hamburg, Germany, 20246
- Novartis Investigative Site
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Tübingen, Germany, 72076
- Novartis Investigative Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- ECOG 0 - 2
- Histologically proven adenocarcinoma of the prostate.
- Patients with CRPC (castration resistant prostate cancer): advanced or metastatic adenocarcinoma of the prostate.
- Prior treatment with a GnRH-agonist or GnRH-antagonist for at least 6 months. The medication must not have been changed for at least 3 months prior to start of study treatment.
Prior treatment with an anti-androgen (e.g. bicalutamide, flutamide, cyproteronacetate) is allowed but not necessary. Patients treated with anti-androgen must have discontinued anti-androgen for at least 6 weeks prior to start of study treatment.
- Dose escalation part only: prior treatment with an anti-androgen and GnRH agonist or antagonist is allowed.
- Dose expansion part only: prior concomitant treatment with an anti-androgen and GnRH agonist or GnRH antagonist for ≤6 weeks is allowed (in order to control flare up).
- Serum testosterone within castration level (<50 ng/dl or < 1,7 nM)
- Disease progression demonstrated by a rising PSA with or without metastases. PSA ≥2 ng/mL at study entry. Rising PSA is defined as two consecutive rises over a nadir value; the individual measurements are obtained at least 1 week apart.
Exclusion criteria:
- Dose expansion part only: Secondary hormonal manipulation of prostate cancer (other than GnRH agonist or antagonist) for more than 6 weeks, including concomitant anti-androgens.
- Prior cytotoxic therapy e.g. with docetaxel, mitoxantrone.
- Patients who have received radiotherapy of target lesions. Patients who have received local radiotherapy of non-target lesions for local symptom control within the last 4 weeks must have recovered from any adverse effects of radiotherapy before recording baseline symptoms. Lesions treated with locoregional therapies within the last 3 months before study inclusion do not qualify as target lesions.
Additional protocol-defined inclusion/exclusion criteria apply.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: SOM230
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Escalation phase: Frequency of dose-limiting toxicities (DLTs) at each dose level associated with monthly administration of pasireotide LAR during the first two treatment cycles by CTCAE version 4.03.
Time Frame: Day 56
|
DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications as defined per study prototol.
These will be evaluated according to the CTCAE v4.03.
|
Day 56
|
Expansion phase: Proportion of patients without PSA-progression at 6 months compared to baseline.
Time Frame: 6 months
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Progression is defined as a PSA-increase of at least 25% and an absolute increase of at least 2 ng/ml from a nadir value, confirmed by a second value four weeks later.
|
6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of adverse drug events, overall and by severity and incidence of serious adverse events and laboratory abnormalities
Time Frame: 3 - 6 months
|
Adverse events will be coded using MedDRA.
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3 - 6 months
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Changes in laboratory assessments, and assessment of physical examinations such as vital signs and electrocardiograms
Time Frame: 3 - 6 months
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Abnormalities according notable criteria (i.e., newly occurring CTC grade 3 or 4 laboratory toxicities) will be identified.
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3 - 6 months
|
Percentage and absolute changes from baseline values in PSA and IGF-1
Time Frame: 3 - 6 months
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3 - 6 months
|
|
Area Under Curve (AUC)
Time Frame: pre-dose, day 21 post dose
|
pre-dose, day 21 post dose
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Proportion of patients without progression at 6 months, defined as PSA-progression (see above) and symptomatic progression of disease and/or progression documented by imaging according to RECIST 1.1
Time Frame: 6 months
|
PSA progression is defined as an increase in PSA of at least 25% compared to baseline and an absolute increase of 2 ng/ml or more from a nadir value.
Symptomatic progression is defined at the investigator's discretion.
Radiological progression is assessed according to RECIST 1.1
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6 months
|
Median progression-free survival (PFS)
Time Frame: 3 - 6 months
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Progression-free survival (PFS) is defined as the time from date of start of treatment to date of event defined as the first documented progression or death due to any cause.
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3 - 6 months
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Median overall survival (OS)
Time Frame: 6 - 15 months
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Overall survival (OS) is defined as the time from date of start of treatment to date of death due to any cause.
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6 - 15 months
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Disease Control Rate by RECIST 1.1 after 6 months
Time Frame: 6 months
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Disease control rate (DCR) is the proportion of patients with a best overall response of CR or PR or SD.
|
6 months
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CSOM230XDE04
- 2010-024399-25 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Castration Resistant Prostate Cancer
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Nuvation Bio Inc.WithdrawnProstate Cancer | Prostate Neoplasm | Cancer of the Prostate | Prostatic Cancer | Castrate Resistant Prostate Cancer | Cancer of Prostate | Castration Resistant Prostatic Cancer | Castration Resistant Prostatic NeoplasmsUnited States
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Janux TherapeuticsRecruitingProstate Cancer | Metastatic Castration-resistant Prostate Cancer | Castration Resistant Prostatic CancerUnited States, Australia
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Universität des SaarlandesRecruitingProstate Cancer Metastatic | Advanced Prostate Carcinoma | Castration Resistant Prostatic CancerGermany
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Myovant Sciences GmbHRecruitingMetastatic Castration-Resistant Prostate Cancer | Metastatic Castration-Sensitive Prostate Cancer | Non-Metastatic Castration-Resistant Prostate CancerUnited States
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Astellas Pharma IncPfizerCompletedCastration-resistant Prostate CancerJapan
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Massachusetts General HospitalBayerCompletedProstate Cancer | Castration-resistant Prostate Cancer | Castration-resistant Prostate Cancer Metastatic to BoneUnited States
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University Hospital, GrenobleTerminatedCastration-resistant Prostate CancerFrance
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Sidney Kimmel Comprehensive Cancer Center at Johns...Clarus TherapeuticsRecruitingProstate Cancer | Castration-resistant Prostate Cancer | Metastatic Castration-resistant Prostate CancerUnited States
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BAMF HealthRecruitingMetastatic Castration-resistant Prostate CancerUnited States
-
Translational Research Center for Medical Innovation...CompletedCastration Resistant Prostate Cancer (CRPC)
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