Ignite Creation Date:
2024-05-05 @ 5:21 PM
Last Modification Date:
2024-10-26 @ 9:30 AM
Study NCT ID:
NCT00432107
Status:
COMPLETED
Last Update Posted:
2015-09-29
First Post:
2007-02-06
Brief Title:
A Study to Assess APO866 for the Treatment of Advanced Melanoma
Sponsor:
Valerio Therapeutics
Organization:
Valerio Therapeutics
Study Overview
Official Title:
A Multi-centre Two-stage Open Label Phase II Study to Assess the Efficacy and Safety of APO866 in the Treatment of Patients With Advanced Melanoma
Status:
COMPLETED
Status Verified Date:
2013-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase II study is designed to determine the efficacy and safety of APO866 for the treatment of patients with advanced cutaneous melanoma APO866 has shown to induce growth inhibition in cultures of human melanoma cells as well as in animal models with subcutaneously implanted melanoma tumors APO866 was considered to be safe and well tolerated in a phase I study that treated 24 patients with advanced cancer In that study one of the two patients with advanced melanoma had a stable disease for 5 months with size reduction of some lesions APO866 is administered by intravenous infusion continuously for 96 hours that is repeated every 4 weeks Patients will receive 3 cycles of treatment and the primary efficacy endpoint will be assessed at Week 16 Patients will be follow-up for 12 months
Detailed Description:
Advanced melanoma is one of the most chemo-resistant types of human cancers The incidence increases by about 25 on an annual basis with may partially be related to aging and growth of the population as well as other environmental risk factors Virtually no recent progress has been made in the treatment of patients with this disease In the past 30 years the FDA has approved only 2 agents dacarbazine and interleukin-2 on the basis of overall response and response duration respectively However these outcomes were not accompanied by a survival benefit The most recent randomized study of Dacarbazine DTIC yielded an overall response rate of 7 and to date no other treatments including combination therapies have shown to improve survival when compared to DTIC alone Hence the mainstay of treatment for patients with advanced melanoma is DTIC-based therapy
APO866 is a novel drug that induces cell death by specifically inhibiting the biosynthesis of Niacinamide Adenine Dinucleotide NAD from niacinamide which is essential for the cellular metabolism protein modification and messenger synthesis APO866 is not subject to the commonly known mechanisms of multi drug resistance MDR Its activity is cell cycle independent APO866 exerted high anti-tumor activity on a broad range of different tumor cells derived from both human solid cancers and leukemias in vitro and on a large number of human xenografts in nude mice including melanoma and rats in vivo Hematologic cancer cells were highly sensitive to APO866 Lymphocytes are the most sensitive normal cells to APO866 resulting in lymphocytopenia and reticulocytopenia in rats monkeys Furthermore APO866 may have anti-angiogenic properties as shown in vivo
APO866 was investigated in 24 patients with advanced cancers in a phase I study aiming to determine the dose-limiting toxicity DLT and maximum tolerated dose MTD Treatment was well tolerated and safe The unique DLT was thrombocytopenia At dose levels higher than 0036 mgm2hr CTC grade III lymphocytopenia not thought to be clinically relevant preceded all other toxicities The recommended dose for phase II studies of APO866 is 0126 mgm2hr administered by civ infusion for 4 consecutive days evry 4 weeks This dose was selected because of its safety profile and the translational observation that Css of APO866 at MTD was similar or higher as compared to the concentrations at which efficacy was established in vitro and in vivo In addition a transient decrease of serum vascular endothelial growth factor VEGF levels a surrogate marker of angiogenesis was observed within 96 hrs after the start of treatment in 9 out of 11 patients treated at MTD and the 0144 mgm2hr dose level of APO866
No objective tumor response was observed However 4 patients had stable disease for at least 3 months prostate cancer 4 months melanoma 5 months sarcomatoid mesothelioma 3 months and oropharyngeal cancer 5 months In addition lesion size reductions were observed in the melanoma patient 80 size reduction and stable size of other lesions at an APO866 dose level of 0072 mgm2hr and in the mesothelioma patient moderate size reductions of pleural lesions at 0108 mgm2hr
Treatment with APO866 was safe and well tolerated The anti-tumor effect of APO866 in particular on melanoma cells in vitro and in vivo and its anti-angiogenic propriety support the rationale to conduct a open phase II study of APO866 in patients with advanced melanoma
APO866 is a novel drug that induces cell death by specifically inhibiting the biosynthesis of Niacinamide Adenine Dinucleotide NAD from niacinamide which is essential for the cellular metabolism protein modification and messenger synthesis APO866 is not subject to the commonly known mechanisms of multi drug resistance MDR Its activity is cell cycle independent APO866 exerted high anti-tumor activity on a broad range of different tumor cells derived from both human solid cancers and leukemias in vitro and on a large number of human xenografts in nude mice including melanoma and rats in vivo Hematologic cancer cells were highly sensitive to APO866 Lymphocytes are the most sensitive normal cells to APO866 resulting in lymphocytopenia and reticulocytopenia in rats monkeys Furthermore APO866 may have anti-angiogenic properties as shown in vivo
APO866 was investigated in 24 patients with advanced cancers in a phase I study aiming to determine the dose-limiting toxicity DLT and maximum tolerated dose MTD Treatment was well tolerated and safe The unique DLT was thrombocytopenia At dose levels higher than 0036 mgm2hr CTC grade III lymphocytopenia not thought to be clinically relevant preceded all other toxicities The recommended dose for phase II studies of APO866 is 0126 mgm2hr administered by civ infusion for 4 consecutive days evry 4 weeks This dose was selected because of its safety profile and the translational observation that Css of APO866 at MTD was similar or higher as compared to the concentrations at which efficacy was established in vitro and in vivo In addition a transient decrease of serum vascular endothelial growth factor VEGF levels a surrogate marker of angiogenesis was observed within 96 hrs after the start of treatment in 9 out of 11 patients treated at MTD and the 0144 mgm2hr dose level of APO866
No objective tumor response was observed However 4 patients had stable disease for at least 3 months prostate cancer 4 months melanoma 5 months sarcomatoid mesothelioma 3 months and oropharyngeal cancer 5 months In addition lesion size reductions were observed in the melanoma patient 80 size reduction and stable size of other lesions at an APO866 dose level of 0072 mgm2hr and in the mesothelioma patient moderate size reductions of pleural lesions at 0108 mgm2hr
Treatment with APO866 was safe and well tolerated The anti-tumor effect of APO866 in particular on melanoma cells in vitro and in vivo and its anti-angiogenic propriety support the rationale to conduct a open phase II study of APO866 in patients with advanced melanoma
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None