An interventional study of oral CFG920 in patients with castration resistant prostate cancer

• Register: EUCTR
• Last refreshed on: 2 June 2014
• Main ID: EUCTR2012-001961-33-ES
• Date of registration: 29/10/2012
• Prospective Registration: Yes
• Primary sponsor: Novartis Farmacéutica S.A.
• Public title: An interventional study of oral CFG920 in patients with castration resistant prostate cancer
• Scientific title: A phase I/II, multicenter, open-label dose finding study of oral CFG920 in patients with metastatic castration-resistant prostate cancer
• Date of first enrolment: 29/01/2013
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-001961-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes 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

Belgium, Canada, France, Singapore, Spain, United States

Contacts

• Name: Javier Malpesa
• Affiliation: Novartis Farmacéutica S.A.

• Name: Javier Malpesa
• Affiliation: Novartis Farmacéutica S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Age > 18 years
2. Eastern Cooperative Oncology Group (ECOG) performance status grade 0-1
3. Suitable venous access for blood sampling
4. Histologically or cytologically confirmed diagnosis of prostate adenocarcinoma 5. Documented metastases determined by bone scan, CT-scan, or MRI
6. Documented ongoing castration condition defined by a serum testosterone levels of < 50 ng/dl (1.7 nmol/L).
7. Documented progressive disease, defined as per the PCWG2 guidelines
8. Minimum washout period of 4 weeks after the use of prostate cancer therapy and 6 weeks after stopping the antiandrogens bicalutamide and MDV3100
9. Anticoagulation is allowed if patients are already on a stable dose of warfarin or low molecular weight heparin for > 2 weeks at time of dose initiation
10. Concomitant use of bisphosphonates is allowed if the dose and renal function have been stable for at least 12 weeks before the enrollment
11. Laboratory values specified in the protocol
12. Patient is capable of understanding and complying with the protocol and has signed the informed consent document prior to the start of screening
Phase I only
13. Patients must have progressed on, are intolerant to, or have refused abiraterone acetate AND have progressed on, are intolerant to, or refused docetaxel
Phase II only
14. Patients must have progressed on, are intolerant to, or have refused docetaxel
Phase I/II abiraterone naïve patients
15. No prior treatment with CYP17 inhibitors or MDV3100
Phase I/II primary abiraterone-resistant CRPC
16. Disease progression while on continuous treatment with ABI or progression up to 30 days after the last dose of ABI
17. No intervening systemic therapy between cessation of ABI and initiation of CFG920 treatment
18. Patient has not demonstrated objective clinical benefit while on continuous treatment with ABI
Phase I/II secondary abiraterone-resistant CRPC
19. Disease progression while on continuous treatment with ABI or progression up to 30 days after the last dose of ABI
20. No intervening systemic therapy between cessation of ABI and initiation of CFG920 treatment
21. Patient demonstrated objective clinical benefit while on continuous treatment with ABI
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 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 90

Exclusion criteria:
1. Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or require increasing doses of steroids to control their CNS disease
2. Major surgery within 28 days before study treatment and/or have not recovered fully from the adverse effects of any major surgical procedures before study treatment
3. Patients who have received radiotherapy ? 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy
4. Chronic steroid therapy other than the following: Daily use of 10 mg prednisone or low dose steroid for the control of nausea and vomiting, topical steroid, or inhaled steroid use.
5. Participation in another clinical trial involving experimental therapy < 4 weeks prior to the first dose of study drug or ongoing in another experimental trial related to the treatment of prostate cancer
6. Current evidence of spinal cord compression, current bilateral hydronephrosis, or current bladder neck outlet obstruction
7. History of another primary malignancy that is currently clinically significant or currently requires active intervention
8. Uncontrolled hypertension despite appropriate medical therapy
9. History of pituitary or adrenal dysfunction
10. Gastrointestinal disorders or gastric by-pass surgery that could interfere with the swallowing and absorption of CFG920
11. Impaired cardiac function or clinically significant cardiac disease
12. History of an active infection requiring systemic therapy within 10 days before study treatment.
13. Known diagnosis of human immunodeficiency virus (HIV) infection
14. Evidence of active hepatitis viral infection such as hepatitis B or hepatitis C or chronic liver disease
15. Patients who are currently receiving prohibited medications listed in the protocol and cannot be discontinued at least 1 week prior to starting CFG920
16. Any condition that in the assessment of the investigator renders the patient not suitable for participation in this clinical study protocol


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

Health Condition(s) or Problem(s) studied

Metastatic prostate cancer
MedDRA version: 14.1 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Code: CFG920
Pharmaceutical Form: Capsule
INN or Proposed INN: CFG920
Current Sponsor code: CFG920
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Product Code: CFG920
Pharmaceutical Form: Capsule
INN or Proposed INN: CFG920
Current Sponsor code: CFG920
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Product Name: Prednisone
Pharmaceutical Form: Tablet
INN or Proposed INN: NA
Other descriptive name: PREDNISONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Primary Outcome(s)

Primary end point(s): Phase I: Incidence rate of dose limiting toxicities (DLT)
Phase II:Rate of patients with PSA response

Secondary Objective: 1. Phase I and II: To characterize the safety and tolerability of CFG920
2. Phase I and II: To characterize the PK of CFG920
3. Phase I : Evaluate preliminary antitumor activity
Phase II
4. Evaluate preliminary antitumor activity
5. Estimate the extent of target inhibition by evaluating the effects of CFG920 on serum hormone levels as potential pharmacodynamic (PD) markers
6. Characterize the relationship between PK and potential PD markers

Main Objective: Phase I:To estimate the Maximum Tolerated Dose (MTD) or recommended phase II dose (RP2D) of oral CFG920 when co-administered with prednisone to adult patients with castration-resistant prostate cancer.
Phase II: To assess preliminary anti-tumor activity of CFG920 across 3 castration-resistant prostate cancer groups:1) Abiraterone- naïve, 2) Abiraterone primary resistant, 3) Abiraterone secondary resistant

Timepoint(s) of evaluation of this end point: Phase I: 1st cycle of treatment
Phase II:baseline, >= 12 weeks

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. 18 months
2. a)18 months, b)1st two cycles of treatment, c) 1st two cycles of treatment
3. 18 months
4. 18 months
5. a) Baseline, until progression of disease, b) enrollment until disease progression, c) and d) 18 months
6. 18 months

Secondary end point(s): Phase I & Phase II
1. Adverse events, serious adverse events, changes in laboratory values, assessments of physical examinations, vital signs, and electrocardiograms
2. PK parameters including but not limited to AUClast, Cmax, Tmax
Phase I
3. PSA response defined as a ?50% reduction in PSA from Baseline to ?12 weeks after first dose of CFG920 that is confirmed 4 weeks later
Phase II
4. Assess the efficacy of the RP2D with the following:
? Progression Free-survival (Time from baseline until progression of disease (according to RECIST 1.1) or progression by bone scan (according PCWG2) or PSA progression (according PCWG2) or death from any cause)
? Radiological PFS (rPFS): time from enrollment until disease progression by RECIST 1.1 or progression by bone scan (PCWG2)
? Proportion of patients with a decrease of ? 50% in the PSA concentration at 12 weeks that is confirmed at 4 weeks later in arm 1, arm 2, and arm 3
? Best PSA response at any time during the study, Time to PSA progression, Overall response rate (ORR) and duration of response according to RECIST 1.1.
5. Evaluate the change from baseline in serum hormones DHEA-S, androstenodione, testosterone, aldosterone, cortisol, 11-deoxycorticosterone, corticosterone
6. Correlate plasma exposure parameters of CFG920 and serum hormones

Secondary ID(s)

CFG920X2101

Source(s) of Monetary Support

Novartis Pharma service AG