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
  Purpose

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).


Condition Intervention Phase
Sarcoma
Drug: KPT-330-003
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by NPM Pharma Inc.:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Other Outcome Measures:
  • 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 ]

Estimated Enrollment: 20
Study Start Date: July 2013
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Drug: KPT-330-003

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01896505

Contacts
Contact: Michael Kauffman, MD PhD +1 508-975-4822 mkauffman@karyopharm.com

Locations
United States, New York
Memorial Sloan Kettering Cancer Centre Recruiting
New York, New York, United States, 10065
Principal Investigator: Gary Schwartz, M.D.         
Canada, Ontario
Princess Margaret Hospital Recruiting
Toronto, Ontario, Canada, M5T 2M9
Principal Investigator: Malcolm J Moore, M.D.         
Sponsors and Collaborators
NPM Pharma Inc.
  More Information

No publications provided

Responsible Party: NPM Pharma Inc.
ClinicalTrials.gov Identifier: NCT01896505     History of Changes
Other Study ID Numbers: KCP-330-003
Study First Received: June 11, 2013
Last Updated: September 11, 2013
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by NPM Pharma Inc.:
bone
soft-tissue
sarcoma
KPT-330
food
effects

Additional relevant MeSH terms:
Sarcoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue

ClinicalTrials.gov processed this record on October 23, 2014