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Hormone Refractory Prostate CancerPhase 2NCT01741116

Dovitinib(TKI258) in Patients With Castration-resistant Prostate Cancer

A Phase 2 study testing TKI258 in people with Hormone Refractory Prostate Cancer, run by Korean Cancer Study Group at 2 sites in South Korea.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The aim of this study is to evaluate efficacy and safety of Dovitinib(TKI258) in patients with castration resistant prostate cancer after failure of docetaxel-based chemotherapy. Further correlative study for metabolic response using PET image and change in serum fibroblast growth factor 23(FGF23) will be conducted. Read more about this study

Who is it for?
Any age, men only
Conditions the study is for
Hormone Refractory Prostate Cancer
What is being tested?
TKI258
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
2 sitesSouth Korea
Study dates
Nov 2012to Oct 2016
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • Men only
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Patients with histologically confirmed progressive metastatic androgen-independent adenocarcinoma of the prostate with radiographic evidence of disease.
  • No more than two previous cytotoxic chemotherapy
  • Castration level of testosterone (< 50 ng/dl) achieved by orchiectomy or gonadotropin-releasing hormone(GnRH) agonist
  • Eastern Cooperative Oncology Group(ECOG) performance status 0 - 2
  • Finished any study drug or chemotherapy earlier than 4 weeks before the first administration of the study drug.
  • Age ≥ 20 years old
Show all 15Show fewer
  • Patients must have the following laboratory values:
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
  • Platelets ≥ 75 x 109/L
  • Hemoglobin (Hgb) > 8 g/dL
  • Serum total bilirubin: ≤ 1.5 x ULN
  • alanine transaminase(ALT) and aspartate aminotransferase(AST) ≤ 2.0 x upper limit of normal(ULN) with or without liver metastases
  • Serum creatinine ≤ 1.5 x ULN or serum creatinine >1.5 - 3 x ULN or 1.5 x ULN<serum creatinine < 3 x ULN, if calculated creatinine clearance (CrCl) is ≥ 30 mL/min using the Cockcroft-Gault equation, see formula below:
  • CrCl = [140-age (years)] x weight (kg) / [72 x serum Cr (mg/dL)] (if patient is female multiply the above by 0.85)
  • Patients who give a written informed consent obtained according to local guidelines

Who cannot join

  • Patients eligible for this study must not meet any of the following criteria
  • Patients with known brain metastases or who have signs/symptoms attributable to brain metastases and have not been assessed with radiologic imaging to rule out the presence of brain metastases
  • Patients with another primary malignancy within 3 years prior to starting study drug, with the exception of adequately treated in-situ carcinoma of the uterine cervix, basal or squamous cell carcinoma or non-melanomatous skin cancer

Trial locations and contacts

2 sites in 1 country.

South Korea2 sites

  • Korean Cancer Study Group

    Seoul, Chongro-ku, 110999

  • Korea University Anam Hospital

    Seoul, Seongbuk-gu, Inchon-ro, 136-705

Other trials in South Korea

About this study

Official title: A Phase II Study of TKI258 in Patients With Castration-resistant Prostate Cancer

The aim of this study is to evaluate efficacy and safety of Dovitinib(TKI258) in patients with castration resistant prostate cancer after failure of docetaxel-based chemotherapy. Further correlative study for metabolic response using PET image and change in serum fibroblast growth factor 23(FGF23) will be conducted.

Read the detailed description

Growth factor signals are important in carcinogenesis and progression of prostate cancer, and fibroblast growth factors (FGF) have important roles in this regard. FGF ligands (FGF1, -2, -6, -8, and -17) and FGF receptors (FGFR1 and FGFR4) have all shown to be significantly overexpressed in prostate cancer1-5. And, the recent studies have demonstrated that the critical roles of the FGF family members are mediated by the signaling between epithelial and stromal compartments, thus, promoting epithelial-mesenchymal transition (EMT)6,7. Moreover, a recent study has shown that FGF-2 is a mediator of second wave angiogenesis and tumor progression in men during the formation of castration-resistant tumors. Therefore, inhibition of signaling via FGF axis might be a viable strategy for the treatment of castration-resistant prostate cancer.

TKI258, an oral multitargeted receptor tyrosine kinase (RTK) inhibitor is known to potently inhibit the class III, IV, and V RTKs, showing biochemical 50 percent inhibitory concentration(IC50) values <20 nmol/L for VEGFRs (VEGFR-1, VEGFR-2, and VEGFR-3); the platelet-derived growth factor receptor-β (PDGFR-β); fibroblast growth factor receptors 1, 2, and 3 (FGFR-1,2,3); fetal liver tyrosine kinase receptor 3 (FLT-3); and KIT Ret, tyrosine kinase A (TrkA), and csf-1 RTKs. Due to the unique inhibitory activity on FGF pathways, TKI258 has shown significant activity in a variety of tumor xenograft models in athymic mice, including acute myeloid leukemia, multiple myeloma, and colon- and prostate-derived models9.

Castration-resistant prostate cancers (CRPC) are one of the challenges in oncology practice. Although there have been advances in chemotherapy10, new hormonal agents11, and immunotherapeutics12, patients in this subgroup still have limited life expectancy. Therefore, there is an urgent need to identify therapeutic targets and clinical development of target agents for the treatment of CRPC. For this end, sorafenib has been tested in multiple phase II studies earlier13-17; however, the clinical efficacy was very limited. The low efficacy of sorafenib might be partly explained by the lower potency in inhibition of RTKs. Considering nanomolar concentration range of IC50 for TKI258 compared with micromolar concentration for other multi-TKIs, the efficacy of TKI258 should be evaluated in CRPC patients.

Being tested
TKI258
Keywords
castration-resistant prostate cancer, TKI258, FGF23

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TKI258Drug

    Also called Dovitinib

    Investigational treatment refers to TKI258 in this study Until Progression, unacceptable toxicity, withdrawal

Study groups in NCT01741116
Study groupRoleWhat they receive
TKI258, inhibitor of RTKsExperimentalIntervention: TKI258 Investigational drug, TKI258, will be administered to all of the patients after enrollments. Treatment will initially be administered as 28-day cycles as follows: - Daily 500mg of TKI258 will be self-administered orally by the patient for 5 days, followed by 2 days of treatment off.
Receives: Drug: TKI258

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 16 week progression free survival rate

    disease progression defined as either the appearance of new lesions or unidimensional tumor measurements increasing >20% or symptomatic progression

    Measured: Week 16

Secondary outcomes (1)

  1. Overall response rate

    Overall response rate per Response Evaluation Criteria in Solid Tumors(RECIST)1.0 and Prostate-specific antigen(PSA), overall survival time, toxicity, and biological effect of TKI258 in patients via correlative study using serum and PET-CT image

    Measured: up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Dec 2012 (estimated)
  2. Study startNov 2012
  3. Primary completionDec 2014
  4. Study completionOct 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
44 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01741116
Sponsor's protocol ID
KCSG-GU11-05
Other IDs
GU11-05
Status last verified
Feb 2021
First submitted
17 Oct 2012
Last updated
18 Feb 2021
Results posted
No
Data monitoring committee
Yes

Publications

  • Dorkin TJ, Robinson MC, Marsh C, Bjartell A, Neal DE, Leung HY. FGF8 over-expression in prostate cancer is associated with decreased patient survival and persists in androgen independent disease. Oncogene. 1999 Apr 29;18(17):2755-61. doi: 10.1038/sj.onc.1202624.

    PubMed 10348350

  • Gnanapragasam VJ, Robinson MC, Marsh C, Robson CN, Hamdy FC, Leung HY. FGF8 isoform b expression in human prostate cancer. Br J Cancer. 2003 May 6;88(9):1432-8. doi: 10.1038/sj.bjc.6600875.

    PubMed 12778074

  • Heer R, Douglas D, Mathers ME, Robson CN, Leung HY. Fibroblast growth factor 17 is over-expressed in human prostate cancer. J Pathol. 2004 Dec;204(5):578-86. doi: 10.1002/path.1668.

    PubMed 15538740

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing TKI258 in people with Hormone Refractory Prostate Cancer, run by Korean Cancer Study Group at 2 sites in South Korea.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

16 week progression free survival rate (time frame: Week 16). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01741116, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2021.

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