Phase 1 Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of Pasireotide LAR in Patients With Castration Resistant Prostate Cancer (MACS1702)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01646684
First received: July 18, 2012
Last updated: July 31, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Castration Resistant Prostate Cancer
Drug: SOM230
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1 Study to Evaluate Safety, and Preliminary Efficacy of Pasireotide LAR in Castration Resistant Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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.

  • Expansion phase: Proportion of patients without PSA-progression at 6 months compared to baseline. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Incidence of adverse drug events, overall and by severity and incidence of serious adverse events and laboratory abnormalities [ Time Frame: 3 - 6 months ] [ Designated as safety issue: Yes ]
    Adverse events will be coded using MedDRA.

  • Changes in laboratory assessments, and assessment of physical examinations such as vital signs and electrocardiograms [ Time Frame: 3 - 6 months ] [ Designated as safety issue: Yes ]
    Abnormalities according notable criteria (i.e., newly occurring CTC grade 3 or 4 laboratory toxicities) will be identified.

  • Percentage and absolute changes from baseline values in PSA and IGF-1 [ Time Frame: 3 - 6 months ] [ Designated as safety issue: No ]
  • Area Under Curve (AUC) [ Time Frame: pre-dose, day 21 post dose ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
    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

  • Median progression-free survival (PFS) [ Time Frame: 3 - 6 months ] [ Designated as safety issue: Yes ]
    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.

  • Median overall survival (OS) [ Time Frame: 6 - 15 months ] [ Designated as safety issue: No ]
    Overall survival (OS) is defined as the time from date of start of treatment to date of death due to any cause.

  • Disease Control Rate by RECIST 1.1 after 6 months [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Disease control rate (DCR) is the proportion of patients with a best overall response of CR or PR or SD.


Estimated Enrollment: 51
Study Start Date: March 2013
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SOM230 Drug: SOM230

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. ECOG 0 - 2
  2. Histologically proven adenocarcinoma of the prostate.
  3. Patients with CRPC (castration resistant prostate cancer): advanced or metastatic adenocarcinoma of the prostate.
  4. 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.
  5. 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.

    1. Dose escalation part only: prior treatment with an anti-androgen and GnRH agonist or antagonist is allowed.
    2. 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).
  6. Serum testosterone within castration level (<50 ng/dl or < 1,7 nM)
  7. 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:

  1. 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.
  2. Prior cytotoxic therapy e.g. with docetaxel, mitoxantrone.
  3. 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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01646684

Contacts
Contact: Novartis Pharmaceuticals +41613241111
Contact: Novartis Pharmaceuticals

Locations
Germany
Novartis Investigative Site Recruiting
Berlin, Germany, 10117
Novartis Investigative Site Recruiting
Dresden, Germany, 01307
Novartis Investigative Site Recruiting
Hamburg, Germany, 20246
Novartis Investigative Site Recruiting
Hannover, Germany, 30625
Novartis Investigative Site Recruiting
Tübingen, Germany, 72076
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Principal Investigator: Arnulf Stenzl, Prof. Dr. med Universitätsklinkikum Tübingen
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01646684     History of Changes
Other Study ID Numbers: CSOM230XDE04, 2010-024399-25
Study First Received: July 18, 2012
Last Updated: July 31, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Novartis:
Prostate cancer, pasireotide LAR, castration resistant prostatate cancer, CRPC, SOM230 LAR

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on August 27, 2014