Clinical Trial 18521

Cancer Type: Gastrointestinal Tumor
Interventions:Abiraterone acetate; Dexamethasone; KPT-8602; Zytiga (Abiraterone acetate)

Study Type: Treatment
Phase of Study: Phase I/II
Investigators:

  • Jingsong Zhang

Overview

Study Title

A Phase 1/2 Open-Label Study of the Safety, Tolerability and Efficacy of the Selective Inhibitor of Nuclear Export (SINE)Compound KPT-8602 in Patients with Relapsed/Refractory Cancer Indications

Summary

The purpose of this study is to find out the highest dose of KPT-8602 that can be given safely, any side-effects that it may cause, how the body affects the study drug concentrations in the blood (pharmacokinetics), the effects of the study drug on the body (pharmacodynamics) and to gain some information on its effectiveness in treating multiple myeloma.

Objective

Primary: - To determine the MTD within the tested dose range for KPT-8602 in RRMM. - To determine the RP2D for KPT-8602 in relapsed/refractory MM, CRC, mCRPC, and higher risk MDS. - To evaluate the safety and tolerability, including DLTs of KPT-8602. - To determine preliminary evidence of anti-tumor activity of KPT-8602 in patients with relapsed/refractory MM, CRC (KRAS wild-type and KRAS mutant), mCRPC, and higher risk MDS according to assessment by any or all of the following: ORR and duration of response (DOR); Progression-free survival (PFS); Overall survival (OS); CBR and duration of CBR; Disease control rate (DCR) and duration of DCR. Secondary: - To determine the PK of KPT-8602, maximum plasma concentration, area under the curve, time-to-peak plasma concentration, terminal half-life, volume of distribution, and clearance rate. Exploratory: - To evaluate correlations of KPT-8602 response with molecular markers relevant to eachtumor type; - To evaluate the PDn and pharmacogenomic correlations of KPT-8602; - To evaluate target engagement of KPT-8602; - To identify possible mechanisms of resistance to KPT-8602.

Inclusion Criteria

  • Evidence of disease progression: Symptomatic relapsed or refractory requiring current treatment. Previously treated with ≥ 3 prior regimens (lines of therapy) that included at least one of each of the following: alkylating agent, immunomodulatory drug, proteasome inhibitor, and a steroid. Must be refractory to most recent anti-cancer regimen.
  • Must have measurable disease defined by one of the following: Serum M-protein ≥ 0.5 g/dL by serum protein electrophoresis (SPEP) or for IgA myeloma, by quantitative IgA If SPEP is felt to be unreliable for routine Mprotein measurement (e.g., for patients with IgA MM), then quantitative Ig levels by nephelometry or turbidometry are acceptable; or Urinary M-protein excretion at least 200 mg/24 hours; or Serum Free Light Chain (Serum FLC) whereby the involved light chain measures ≥ 10 mg/dL and with an abnormal ratio.

  • Exclusion Criteria

  • Time since the last prior therapy: Radiation, chemotherapy, immunotherapy or any other anticancer therapy, including investigational anticancer therapy ≤ 2 weeks prior to Cycle 1 Day 1; Palliative steroids for disease related symptoms are allowed up to 3 days prior to Cycle 1 Day 1.
  • Active graft versus host disease after allogeneic stem cell transplantation. At least 3 months must have elapsed since completion of allogeneic stem cell transplantation.
  • Active central nervous system malignancy. Potential participants who have only had prophylactic intrathecal or intravenous chemotherapy against central nervous system disease are eligible.
  • Significantly diseased or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea that could interfere with the absorption of KPT-8602.
  • Prior exposure to XPO1 inhibitors.
  • Life expectancy of ≥ 4 months.