NCT02728492

Safety, Tolerability and Pharmacokinetics of Quisinostat, a Histone Deacetylase Inhibitor, in Combination With Chemotherapy

Open-label Multicenter Multiple Ascending Dose Study to Evaluate Safety, Tolerability and Pharmacokinetics of Quisinostat, a Histone Deacetylase Inhibitor, in Combination With Gemcitabine + Cisplatin Chemotherapy (Second Line for Patients With Non-small Cell Lung Cancer) or Paclitaxel + Carboplatin Chemotherapy (Second Line for Patients With Non-small-cell Lung Cancer, Second and Subsequent Lines for Patients With Epithelial Ovarian Cancer)

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 51 (actual)
• Sponsor: NewVac LLC · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Quisinostat besides its own efficacy, which can potentially lead to better results of polychemotherapy and increase the mean time to progression, it may be demonstrated that Quisinostat leads to sustained tumor sensitivity to platinum drugs. In this study safety and tolerability of multiple administrations of Quisinostat in doses ranging from 8 mg to 12 mg combined with standard backbone chemotherapy in patients with non-small cell lung cancer (second line) and ovarian cancer (second and subsequent lines) will be investigated.

Detailed description

It was proven that Quisinostat increases HDAC1-inhibited E-cadherin expression (at the low concentrations of 30 nM) which increases susceptibility to epidermal growth factor inhibitors in case of non-small-cell lung cancer and stops proliferation of paclitaxel-resistant cells. Thus, besides its own efficacy, which can potentially lead to better results of polychemotherapy and increase the mean time to progression, it may be demonstrated that Quisinostat leads to sustained tumor sensitivity to platinum drugs and possibly to resensitiztion in case of acquired or primary resistance. The main objective of the study is to evaluate the safety and tolerability of Quisinostat in multiple ascending doses and establish its maximum tolerated dose (MTD), administered in combination with standard backbone chemotherapy, as follows: Gemcitabine + Cisplatin in patients with non-small-cell lung cancer (second line) and Paclitaxel + Carboplatin in patients with non-small-cell lung cancer (second line) and in patients with ovarian cancer (second and subsequent lines). MTD is defined as maximum dose at which DLT occurs in no more than 1 patient of 6. Secondary objectives are: • Study of pharmacokinetics (PK) of multiple dosing of Quisinostat administered in combination with chemotherapy, as follows: Gemcitabine + Cisplatin in patients with non-small-cell lung cancer (second line) and Paclitaxel + Carboplatin in patients with non-small-cell lung cancer (second line) and in patients with ovarian cancer (second and subsequent lines) Preliminary estimation of possible effect of the drug, added to chemotherapy, on tumor growth.

Conditions

• Non-small Cell Lung Cancer
• Epithelial Ovarian Cancer

Interventions

Type	Name	Description
DRUG	Quisinostat
DRUG	Paclitaxel
DRUG	Carboplatin
DRUG	Gemcitabine
DRUG	Cisplatin

Timeline

• Start date: 2013-08-01
• Primary completion: 2015-12-01
• Completion: 2016-01-01
• First posted: 2016-04-05
• Last updated: 2016-05-03

Locations

6 sites across 1 country: Russia