A Phase I Trial to Assess the Effects of Food and Formulation on PK of KPT-330 in Patients With Sarcoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by NPM Pharma Inc.
Sponsor:
Information provided by (Responsible Party):
NPM Pharma Inc.
ClinicalTrials.gov Identifier:
NCT01896505
First received: June 11, 2013
Last updated: September 11, 2013
Last verified: September 2013

June 11, 2013
September 11, 2013
July 2013
December 2013   (final data collection date for primary outcome measure)
  • Area under the plasma concentration versus time curve (AUC) of KPT-330 [ Time Frame: At baseline (time 0) and on Day 1 of weeks 1 - 4 in Cycle 1 at the following timepoints:15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10,18 and 24 hours post dose ] [ Designated as safety issue: Yes ]
  • Peak Plasma Concentration (Cmax) of KPT-330 [ Time Frame: At baseline (time 0) and on Day 1 of weeks 1 - 4 in Cycle 1 at the following timepoints:15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10,18 and 24 hours post dose ] [ Designated as safety issue: Yes ]
  • Comparison of AUC and Cmax of KPT-330 between: Treatment A vs B; Treatment C vs D; Treatment A vs C [ Time Frame: At baseline (time 0) and on Day 1 of weeks 1 - 4 in Cycle 1 at the following timepoints:15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10,18 and 24 hours post dose ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01896505 on ClinicalTrials.gov Archive Site
  • Tumor response in sarcoma patients (RECISTv1.1 criteria) [ Time Frame: CT scans will be done at 8 weeks post dose and every 2 months while on study drug; and 30 days after the last dose in the study. ] [ Designated as safety issue: Yes ]
  • Change in laboratory parameters (serum chemistry, hematology and urinalysis) [ Time Frame: Baseline and Day 1 of weeks 1 -4 in Cycle 1 ] [ Designated as safety issue: Yes ]
  • Change in ECG parameters [ Time Frame: Baseline and Day 1 of each week (weeks 1-4) in Cycle 1 ] [ Designated as safety issue: Yes ]
  • Change in Vital sign parameters (Systolic pressure, diastolic pressure and heart rate) [ Time Frame: Baseline and on Day 1 of each week (weeks 1 - 4) of Cycle 1 ] [ Designated as safety issue: Yes ]
  • Number and percentages of patients involved per CTCAE Category and CTCAE Term [ Time Frame: After first dose of drug until final study visit ] [ Designated as safety issue: Yes ]
  • Highest relation of an AE to study drug [ Time Frame: After first dose until final visit ] [ Designated as safety issue: Yes ]
  • Maximum AE severity [ Time Frame: After first dose of study drug until the final study visit ] [ Designated as safety issue: Yes ]
Same as current
Biomarker changes on sarcoma biopsy specimens (in patients who can safely undergo biopsy). [ Time Frame: Baseline and Week 3 or 4 of Cycle 1 ] [ Designated as safety issue: No ]
Same as current
 
A Phase I Trial to Assess the Effects of Food and Formulation on PK of KPT-330 in Patients With Sarcoma
An Open Label Phase IB Trial to Evaluate the Effects of Food and Formulation on Pharmacokinetics of the Oral Selective Inhibitor of Nuclear Export (SINE) KPT-330 in Patients With Soft-Tissue or Bone Sarcoma

The purpose of this research study is to find out more information such as: to determine the effects of high and low fat foods on the pharmacokinetics (PK) of oral KPT-330 tablets, to compare PK of capsules and tablets, to assess the effects of KPT-330 on cellular morphology and biomarker changes on sarcoma biopsy specimens (in patients who can safely undergo biopsy).

Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Sarcoma
Drug: KPT-330-003
  • Arm 1 - Treatment A, B, C, D

    There are 4 treatment formulations:

    A: fasted, tablet formulation B: high-fat meal, tablet formulation C: low-fat meal, tablet formulation D: low-fat meal, capsule formulation

    In Arm 1, the following order will be utilized:

    Week 1, day 1: Treatment A Week 2, day 1: Treatment B Week 3, day 1: Treatment C Week 4, day 1: Treatment D

    Intervention: Drug: KPT-330-003
  • Arm 2 - Treatment B, A, D, C

    There are 4 treatment formulations:

    A: fasted, tablet formulation B: high-fat meal, tablet formulation C: low-fat meal, tablet formulation D: low-fat meal, capsule formulation

    In Arm 1, the following order will be utilized:

    Week 1, day 1: Treatment C Week 2, day 1: Treatment A Week 3, day 1: Treatment D Week 4, day 1: Treatment C

    Intervention: Drug: KPT-330-003
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
20
December 2014
December 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Written informed consent in accordance with federal, local, and institutional guidelines
  2. Age ≥18 years
  3. Patients must have histologically confirmed soft tissue or bone/cartilage sarcoma. Patients with sarcoma of small round blue cell tumor types are allowed. Gastrointestinal stromal tumors (GIST) are excluded.
  4. Patients must have received at least one prior anticancer regimen for metastatic disease unless there is no other therapy available and evidence of progressive disease on study entry. Patients with stable disease will be included if there has been failure to respond to another drug(s) within the previous 3 months
  5. Eastern Cooperative Oncology Group Performance status of 0-1
  6. Adequate hematopoietic function:

    • total white blood cell (WBC) count ≥2000/mm3
    • absolute neutrophil count (ANC) ≥1000/mm3
    • platelet count ≥100,000/mm3
  7. Adequate hepatic function:

    • bilirubin <1.5 × the upper limit of normal (ULN)
    • alanine aminotransferase (ALT) <2 × ULN
  8. Adequate renal function: estimated creatinine clearance of ≥ 30 mL/min calculated using the formula of Cockroft and Gault: (140-Age) • Mass (kg)/(72 • creatinine mg/dL); multiply by 0.85 if female
  9. Female patients of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential. Acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal. For both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose

Exclusion Criteria:

  1. Patients who are pregnant or lactating
  2. Patients with known liver metastases
  3. Radiation, chemotherapy, immunotherapy, any other systemic anticancer therapy or participation in an investigational anti-cancer study ≤ 3 weeks prior to initiation of therapy
  4. Major surgery within four weeks before initiation of therapy
  5. Unstable cardiovascular function:

    • symptomatic ischemia, or
    • uncontrolled clinically significant conduction abnormalities (e.g.: ventricular tachycardia on antiarrhythmics are excluded and 1st degree AV block or asymptomatic LAFB/RBBB will not be excluded) or
    • congestive heart failure (CHF) of NYHA Class ≥3, or
    • myocardial infarction (MI) within 3 months of initiation of therapy
  6. Active, uncontrolled infection within one week prior to first dose
  7. Known to be HIV seropositive
  8. Known active hepatitis A, B, or C infection; or known to be positive for HCV RNA or HBsAg (HBV surface antigen)
  9. Patients with known brain metastasis
  10. Patients with any gastrointestinal dysfunctions that could interfere with the interpretation of the food effect data
  11. Patients with known intolerance to low or high fat meals
  12. In the opinion of the investigator, patients who are significantly below their ideal body weight
  13. Serious psychiatric or medical conditions that could interfere with treatment
  14. Concurrent therapy with approved or investigational anticancer therapeutic including topical therapies
Both
18 Years and older
No
Contact: Michael Kauffman, MD PhD +1 508-975-4822 mkauffman@karyopharm.com
United States,   Canada
 
NCT01896505
KCP-330-003
No
NPM Pharma Inc.
NPM Pharma Inc.
Not Provided
Not Provided
NPM Pharma Inc.
September 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP