Dovitinib(TKI258) in Patients With Castration-resistant Prostate Cancer
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|ClinicalTrials.gov Identifier: NCT01741116|
Recruitment Status : Unknown
Verified November 2012 by Kyong-Hwa, Park, Korean Cancer Study Group.
Recruitment status was: Recruiting
First Posted : December 4, 2012
Last Update Posted : December 4, 2012
|Condition or disease||Intervention/treatment||Phase|
|Hormone Refractory Prostate Cancer||Drug: TKI258||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||44 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of TKI258 in Patients With Castration-resistant Prostate Cancer|
|Study Start Date :||November 2012|
|Estimated Primary Completion Date :||October 2014|
|Estimated Study Completion Date :||June 2016|
Experimental: TKI258, inhibitor of RTKs
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.
Investigational treatment refers to TKI258 in this study Until Progression, unacceptable toxicity, withdrawal
Other Name: Dovitinib
- 16 week progression free survival rate [ Time Frame: Week 16 ]disease progression defined as either the appearance of new lesions or unidimensional tumor measurements increasing >20% or symptomatic progression
- Overall response rate [ Time Frame: up to 24 months ]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
- Overall survival [ Time Frame: up to 36 months ]
Overall survival is defined as the time from date of randomization to date of death due to any cause. If the patient is not known to have died, survival will be censored at the date of the last contact. Overall survival will be analyzed at the final analysis cut-off date.
The Kaplan-Meier product-limit method will be used to describe the overall survival for the study drug (median, 95% confidence intervals, and plots).
- Serum FGF23 [ Time Frame: 2 months after chemotherapy ]
The objective of the exploratory biomarker is to identify a biomarker 'profile' of a patient population most likely to benefit from treatment with TKI258.
Since this clinical trial was not designed to address specific biomarkers-related hypotheses, the analysis of this data should be viewed as exploratory and hypotheses generating.
- PET-CT [ Time Frame: 2 months after chemotherapy ]The objective of the exploratory biomarker is to identify a biomarker 'profile' of a patient population most likely to benefit from treatment with TKI258.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01741116
|Contact: Kyong Hwa Park, MD, phD||+82-2-920-5983 ext email@example.com|
|Korea, Republic of|
|Korean Cancer Study Group||Recruiting|
|Seoul, Chongro-ku, Korea, Republic of, 110999|
|Contact: So-Yeon Kang 82-2-3276-3511 firstname.lastname@example.org|
|Korea University Anam Hospital||Recruiting|
|Seoul, Seongbuk-gu, Inchon-ro, Korea, Republic of, 136-705|
|Contact: Kyong Hwa Park, MD, phD +82-2-920-5983 ext 5980 email@example.com|
|Principal Investigator:||Kyong Hwa Park, MD, phD||Korea University|