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

NCT01646684 | Completed Phase 1

• 2 other identifiers: CSOM230XDE042010-024399-25
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 4

Brief Summary

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

Conditions

Castration Resistant Prostate Cancer

Keywords

Prostate cancer, pasireotide LAR, castration resistant prostatate cancer, CRPC, SOM230 LAR

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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 Outcomes (8)

• Incidence of adverse drug events, overall and by severity and incidence of serious adverse events and laboratory abnormalities

  3 - 6 months

• Changes in laboratory assessments, and assessment of physical examinations such as vital signs and electrocardiograms

  3 - 6 months

• Percentage and absolute changes from baseline values in PSA and IGF-1

  3 - 6 months

• Area Under Curve (AUC)

  pre-dose, day 21 post dose

• 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

  6 months

Study Arms (1)

SOM230

EXPERIMENTAL

Drug: SOM230

Interventions

SOM230 DRUG

SOM230

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (4)

Novartis Investigative Site

Berlin, 10117, Germany

Location

Novartis Investigative Site

Dresden, 01307, Germany

Location

Novartis Investigative Site

Hamburg, 20246, Germany

Location

Novartis Investigative Site

Tübingen, 72076, Germany

Location

Related Links

• Results for CSOM230XDE04 can be found on the Novartis Clinical Trial Results Website

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

pasireotide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2012
• First Posted: July 20, 2012
• Study Start: March 8, 2013
• Primary Completion: November 13, 2018
• Study Completion: November 13, 2018
• Last Updated: December 21, 2020

Record last verified: 2019-10

Locations

DE (4)