Back to results

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

Primary Purpose

Castration Resistant Prostate Cancer

Status

Completed

Phase

Phase 1

Locations

Germany

Study Type

Interventional

Intervention

SOM230

About this trial

This is an interventional treatment trial for Castration Resistant Prostate Cancer focused on measuring Prostate cancer, pasireotide LAR, castration resistant prostatate cancer, CRPC, SOM230 LAR

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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.
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).
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.

Sites / Locations

Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

SOM230

Arm Description

Outcomes

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.

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.

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

Adverse events will be coded using MedDRA.

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

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

Area Under Curve (AUC)

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

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)

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)

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

Disease control rate (DCR) is the proportion of patients with a best overall response of CR or PR or SD.

Full Information

NCT ID

NCT01646684

First Posted

July 18, 2012

Last Updated

December 17, 2020

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01646684

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2019

Overall Recruitment Status

Completed

Study Start Date

March 8, 2013 (Actual)

Primary Completion Date

November 13, 2018 (Actual)

Study Completion Date

November 13, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Castration Resistant Prostate Cancer

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

SOM230

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

SOM230

Primary Outcome Measure Information:

Title

Description

Time Frame

Day 56

Title

Expansion phase: Proportion of patients without PSA-progression at 6 months compared to baseline.

Description

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.

Time Frame

6 months

Secondary Outcome Measure Information:

Title

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

Description

Adverse events will be coded using MedDRA.

Time Frame

3 - 6 months

Title

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

Description

Abnormalities according notable criteria (i.e., newly occurring CTC grade 3 or 4 laboratory toxicities) will be identified.

Time Frame

3 - 6 months

Title

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

Time Frame

3 - 6 months

Title

Area Under Curve (AUC)

Time Frame

pre-dose, day 21 post dose

Title

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

Description

Time Frame

6 months

Title

Median progression-free survival (PFS)

Description

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.

Time Frame

3 - 6 months

Title

Median overall survival (OS)

Description

Overall survival (OS) is defined as the time from date of start of treatment to date of death due to any cause.

Time Frame

6 - 15 months

Title

Disease Control Rate by RECIST 1.1 after 6 months

Description

Disease control rate (DCR) is the proportion of patients with a best overall response of CR or PR or SD.

Time Frame

6 months

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Berlin

ZIP/Postal Code

10117

Country

Germany

Facility Name

Novartis Investigative Site

City

Dresden

ZIP/Postal Code

01307

Country

Germany

Facility Name

Novartis Investigative Site

City

Hamburg

ZIP/Postal Code

20246

Country

Germany

Facility Name

Novartis Investigative Site

City

Tübingen

ZIP/Postal Code

72076

Country

Germany

12. IPD Sharing Statement

Links:

URL

https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17564

Description

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

Learn more about this trial

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

We'll reach out to this number within 24 hrs