Safety and Pharmacokinetic Study of CVM-1118 Extended-Release in Advanced Cancer Patients
Condition: Advanced Cancer
MeSH terms: Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      CVM-1118 Immediate-release (IR) Capsule and CVM-1118 Extended-release (ER) Capsule are
      proprietary oncology products developed by TaiRx, Inc. for the treatment of patients
      suffering from advanced cancer. Due to the short elimination half-life of CVM-1118 IR
      capsules, the extended release (ER) formulation, containing mini-tablets in hard capsule, has
      been developed to prolong the drug absorption and longer exposure after oral administration.
      The designed dose of CVM-1118 ER was 200 mg per capsule to provide a more patient-compliant
      and safe dosage of CVM-1118. The clinical study CVMEX-001 is therefore designed to evaluate
      the safety and pharmacokinetics of CVM-1118 extend release (ER) Capsule (200 mg/capsule) in
      patients with advanced cancer.
    

Detailed description: 
      The CVM-1118 ER Capsule will be orally administered BID or TID before meal in 28-day
      treatment cycles. Patients will receive 400, 600, 800 to 1,200 mg of CVM-1118 ER Capsule in
      sequential cohort based on safety and dose tolerability. A single-patient cohort per dose
      level (accelerated titration design) will be applied to the first two cohorts, 400 and 600 mg
      daily, and followed by the conventional 3+3 dose escalation design from the dose level of 800
      mg/day. Within the first two cohorts, if any Grade 2 or greater toxicity at least possibly
      attributable to CVM-1118 ER capsule is reported in the first patient during first cycle, a
      single-patient cohort will be converted to conventional 3+3 study design once and expand to a
      minimum of 3 evaluable patients for assessment of toxicity within the first cycle. Dose
      escalation will occur until DLT occurs in 2 or more patients within a dose level. In any
      cohort, if 1 patient experiences a DLT, 3 additional patients will be enrolled to that dose
      level. If 2 or more patients experience a DLT, no further dose escalation will occur. Plasma
      pharmacokinetics samples will be collected at pre-determined time-points for all patients
      participating in the dose-escalation study.

      This study will be completed and closed once the MTD is determined for CVM-1118 ER capsules.
      However, at the end of 4 cycles, it is recommended that some patients should continue
      receiving the clinical benefit from CVM-1118 ER capsules. Thus, patients may be continuously
      treated at the assigned dose level or next higher dose level provided it has been shown to be
      safe in a previously treated cohort by safety committee, until the treating physician feels
      the patient is no longer benefiting from the treatment, or CVM-1118 ER Capsule becomes
      commercially available, as applicable in the country in which the patient lives. In the event
      of unacceptable toxicity at a given dose, CVM-1118 can be reduced to the previous dose level
      or suggested lower dose by PI. If unacceptable toxicity persists despite 2 dose reductions,
      the patient should be removed from study.
    

Intervention name(s): CVM-1118 Extended-Release (ER) Capsules (200 mg/capsule)
Intervention type(s): Drug
Intervention description(s): Patients will receive initial dose regimen: 400 mg of CVM-1118 ER Capsule per day (200 mg BID) in a 28-day cycle for 4 cycles.
Dose escalates from 400, 600, 800, to 1200 mg of CVM-1118 ER capsules with either BID or TID dosing.
A single-patient cohort per dose level (accelerated titration design) will be applied to the first two cohorts, 400 and 600 mg daily, and followed by the conventional 3+3 dose escalation design from the dose level of 800 mg/day.
If 2 or more patients experience a DLT, no further dose escalation will occur.
Other intervention name(s): TRX-818 ER
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Oncology; Advanced Solid Malignancy; Tumor Response; Safety and pharmacokinetics