A single stage phase II, multi-centre, open label study of Glivec in combination with pioglitazone, etoricoxib, dexamethasone and low-dose treosulfane for anti-inflammatory and angiostatic treatment in patients with hormone-refractory prostate cancer

• Register: EUCTR
• Last refreshed on: 24 August 2015
• Main ID: EUCTR2006-000218-19-DE
• Date of registration: 09/10/2006
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma GmbH
• Public title: A single stage phase II, multi-centre, open label study of Glivec in combination with pioglitazone, etoricoxib, dexamethasone and low-dose treosulfane for anti-inflammatory and angiostatic treatment in patients with hormone-refractory prostate cancer
• Scientific title: A single stage phase II, multi-centre, open label study of Glivec in combination with pioglitazone, etoricoxib, dexamethasone and low-dose treosulfane for anti-inflammatory and angiostatic treatment in patients with hormone-refractory prostate cancer
• Date of first enrolment: 21/05/2008
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-000218-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Germany

Key inclusion & exclusion criteria

Inclusion criteria:
• Histologically confirmed prostate carcinoma, which has proven progression after androgen deprivation therapy (surgical or medicinal castration).
• Status of hormone refractory prostate cancer (HRPC) according to EAU-guideline.
• Patients must have increasing PSA levels (within 3 months prior to enrollment) with at least two consecutively increasing PSA levels. The first measurement must be above a reference value and has to be assessed at least one week after the reference value. The second confirmatory measurement taken must be greater than the first measurement and has to be assessed at least one week after the first measurement. If however the second confirmatory measurement is not higher than the first measurement then a third confirmatory measurement at least one week after the second measurement must be performed. The patient is eligible if the third confirmatory measurement is higher than the first measurement. The difference between consecutive PSA values must be at least 5% increase.
• PSA value before inclusion (second or third confirmatory measurement) must be at least 5 ng/ml
• At least 18 years of age.
• Serum testosterone levels must be within range of castration (<50ng/dl or < 1.73nmol/l).
• Sufficient bone marrow function: neutrophils ? 2000/µl, hemoglobin ? 10 g/dl, and platelets ? 100x109/l
• ECOG performance status 0 – 2
• Required laboratory results:
a) Liver function: Total bilirubin = 2.,5 times of upper limit of local institution, SGPT, SGOT = 2.,5 x times of upper limit of local laboratory.
b) Renal function: Creatinine = 1.,3 mg/dl.
• Normal cardiac function.
• Life expectancy at least 6 months.
• Written informed consent of the patient prior to screening procedures.
• Patient must be available for scheduled visits.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Patients with bladder cancer or bladder cancer in their medical history
• Macrohematuria of unknown origin
• Patients with risk factors for bladder cancer (such as exposure to aromatic amines or heavy Tobacco smokers); in light of age-related risks, the balanve of benefits and risks shoukd be considered carefully both before initiating and during treatment in the elderly.
• Prior chemotherapy
• Therapy with Imatinib, or therapy with other inhibitors of tyrosinkinase.
• Second neoplasm diagnosed within 5 years before study start.
• Patients who require therapy with warfarin (Coumadin®), or phenprocoumon (Marcumar) or any other oral anticoagulant (see Section 6.5.3.).
• Known diagnosis of HIV, hepatitis B, or hepatitis C infection.
• Severe, unstable, or uncontrolled medical disease which would confound diagnoses or evaluations required by the protocol, including symptomatic congestive heart failure (NYHA II to IV, see Post-text supplement 6), uncontrolled diabetes, chronic hepatic or renal disease, active uncontrolled infection and chronic inflammatory intestinal disease, auto-immune diseases and angina pectoris
• Inability of performing scheduled visits.
• Surgical therapy within 4 weeks before inclusion.
• Prior therapy with isotopes is not allowed. This includes each radiopharmaceutical li´censed for palliation in prostate cancer or painful osseous metastatic disease, like phosphorus, strontium, rhenium or samarium.
• Radiation therapy to > 25% of bone marrow within 4 weeks before inclusion.
• Controlled filiae in brain.
• Regular blood transfusions.
• Concomitant therapy with other tumor treatment except LHRH agonists.
• Treatment with other experimental substances within 30 days before study start.
• Participation in another clinical trial within 30 days before study start or during the trial.
• Unwilling or unable to comply with the protocol.



Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

prostrate carcinoma
MedDRA version: 14.0 Level: LLT Classification code 10036921 Term: Prostate carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Trade Name: Glivec Filmtabletten 400 mg
Product Name: Glivec Filmtabletten
Product Code: STI571
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Imatinib (as mesylate)
CAS Number: 220127-57-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-

Trade Name: Ovastat
Product Name: Ovastat
Pharmaceutical Form: Capsule
INN or Proposed INN: Treosulfan
CAS Number: 299-75-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-

Trade Name: Arcoxia 60 mg Filmtabletten
Product Name: Arcoxia 60 mg Filmtabletten
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Etoricoxib
CAS Number: 202409-33-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 60-

Trade Name: Actos 30 mg Tabletten
Product Name: Actos 30 mg Tabletten
Pharmaceutical Form: Tablet
INN or Proposed INN: Pioglitazone Hydrochloride
CAS Number: 112529154
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-

Trade Name: Fortecortin 0,5 mg Tabletten
Product Name: Fortecortin 0,5 mg Tabletten
Pharmaceutical Form: Tablet
INN or Proposed INN: Dexamethasone
CAS Number: 50-02-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-

Trade Name: Glivec Filmtabletten 100 mg
Product Name: Glivec Filmtabletten
Product Code: STI571
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Imatinib (as mesylate)
CAS Number: 220127-57-1
Current Sponsor code: STI571
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Trade Name: Actos 15 mg
Product Name: Actos 15 mg
Pharmaceutical Form: Tablet
INN or Proposed INN: PIOGLITAZONE HYDROCHLORIDE
CAS Number: 112529154
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-

Primary Outcome(s)

Primary end point(s): The primary variable is the biochemical (PSA) response rate of patients treated with Glivec® in combination with pioglitazone (Actos®), etoricoxib (Arcoxia®), dexamethasone (Fortecortin®) and Treosulfane (Ovastat®). A patient will be defined as a responder if a PSA decline of at least 50%, which must be confirmed by a second PSA value four weeks later, is observed.

Secondary Objective: The secondary objectives of this study are:
• To evaluate time to PSA response.
• To evaluate the progression-free survival (PFS).
• To evaluate the overall survival rate.
• To evaluate quality of life.
• To evaluate the tolerability and safety of the combined therapy.

Main Objective: To investigate the effect of a treatment with Imatinib mesylate (Glivec®), Pioglitazone (Actos®), Dexamethasone (Fortecortin®) and Etoricoxib (Arcoxia®) in combination with metronomic chemotherapy (Treosulfane: Ovastat®) on the PSA- response rate in patients with hormone refractory prostate cancer.

Secondary ID(s)

CSTI571BDE59