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Safety Study of the Selective Inhibitor of Nuclear Export (SINE) KPT-330 in Patients With Advanced or Metastatic Solid Tumor Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2015 by Karyopharm Therapeutics, Inc
Sponsor:
Information provided by (Responsible Party):
Karyopharm Therapeutics, Inc
ClinicalTrials.gov Identifier:
NCT01607905
First received: May 16, 2012
Last updated: January 13, 2015
Last verified: January 2015
  Purpose

The purpose of this research study is to find out more information such as: the highest dose of KPT-330 that can be given safely, the side effects it may cause, to examine how the body affects the study drug concentrations in the blood (pharmacokinetics or PK), to examine the effects of this study drug on the body (pharmacodynamics or PDn) and to gain some information on its effectiveness in treating cancer.


Condition Intervention Phase
Solid Tumor
Drug: KPT-330
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of the Safety, Pharmacokinetics and Pharmacodynamics of Escalating Doses of the Selective Inhibitor of Nuclear Export/SINE Compound KPT-330 in Patients With Advanced or Metastatic Solid Tumor Malignancies

Resource links provided by NLM:


Further study details as provided by Karyopharm Therapeutics, Inc:

Primary Outcome Measures:
  • Number of participants with Adverse Events [ Time Frame: 2 and 12 months ] [ Designated as safety issue: Yes ]
    Severity of Adverse Events


Secondary Outcome Measures:
  • Area under the plasma concentration versus time curve (AUC) of KPT-330 [ Time Frame: 2 and 12 months ] [ Designated as safety issue: No ]
    Changes in AUC over time


Estimated Enrollment: 190
Study Start Date: June 2012
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Solid Tumors Drug: KPT-330

Schedule 1: Starting dose of KPT-330 will be 3mg/m2 (PO) 3X/week every other day, (QODx3/wk) for weeks 1 and 3. For weeks 2 and 4, drug will be dosed on days 1 and 3.

Schedule 2: Starting dose of KPT-330 will be > 12mg/m2 (PO) 3X/week every other day for week -1; QODx3/wk for weeks 1 and 3. For weeks 2 and 4 drug will be dosed on days 1 and 3. For cycles 2 and beyond, drug admin will be 3X/week every other day, (QODx3/wk) for weeks 1 and 3. For weeks 2 and 4, drug will be dosed on days 1 and 3.

Schedule 3: Starting dose will be ≥ 30mg/m2, 2x/week on days 1 and 3 of each week.

Schedule 4: Starting dose will be ≥ 20mg/m2, 2x/week on consecutive days 1 and 2 of each week.

Schedule 5: Starting dose will be ≥ 30mg/m2, 2x/week on days 1 and 4 of each week.

Schedule 6: Starting dose will be ≥ 20mg/m2, twice a week on days 1 and 4 of each week.

Schedule 7: Once weekly schedule for doses ≥ 50mg/m2

Schedule 8: Twice weekly schedule for ≥45 mg/m2 doses

Other Name: Selinexor

  Eligibility

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

Inclusions Criteria:

  1. Dose Escalation Phase: Patients with advanced or metastatic solid tumors for which no standard therapy is available. For Schedule 6 only: patients with colorectal cancer with liver metastasis.

    Dose Expansion Phase: Previously treated, metastatic or advanced recurrent malignancy with 1 of the following diagnoses, which has been confirmed histologically or cytologically:

    • Up to 12 patients with metastatic colorectal cancer with a history of progression or recurrence following prior fluoropyrimidine, irinotecan and platinum containing regimens as well as bevacizumab. In addition, patients with Kras wild type tumor must have received at least one EGFR blocker.
    • Up to 6 patients with histological or cytological documentation of advanced ovarian, fallopian tube, or primary peritoneal carcinoma with a history of progression or recurrence following at least one prior platinum and one taxane based chemotherapy
    • Up to 12 patients with incurable Squamous cell cancers as follows:

      1. A minimum of 4 Squamous Non-Small Cell Lung Cancer (Sq-NSCLC)
      2. A minimum of 4 Squamous Cell Carcinomas of the Head and Neck (Sq-HNC)
      3. Squamous Cell Carcinoma of the Cervix (SqCC) All patient with Squamous Cell Carcinomas should have a documented history of progression or recurrence following at least one prior platinum based chemotherapy or chemotherapy/radiation containing regimen
    • Up to 6 patients with castration-resistant prostate cancer (CRPC) that was pathologically confirmed as adenocarcinoma of the prostate and with evidence of metastatic disease on bone scan or other imaging. Patient must have progressive disease after at least one hormonal treatment and one cytotoxic therapy e.g. with docetaxel, mitoxantrone.
    • Up to 6 patients with recurrent/relapsed glioblastoma multiforme (GBM/AnaA) or with grade 3 anaplastic astrocytomas that with a history of progression or recurrence following radiotherapy and an alkylating agent (e.g. temozolomide) Patients with other disease types may be enrolled into the expansion phase upon approval of the Sponsor.
  2. Dose Escalation Phase: Patients have exhausted, or be deemed to not benefit from, further conventional therapy and have evidence of progressive disease on study entry.

Both Doses Escalation and Expansion Phases: There is no upper limit on the number of prior treatments provided all inclusion/exclusion criteria are met. Hormone ablation therapy is considered an anticancer regimen. Radiation and surgery are not considered anticancer regimens.

Exclusions Criteria:

  1. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤3 weeks prior to cycle 1 day 1 and mitomycin C and radioimmunotherapy 6 weeks prior to cycle 1 day 1;
  2. Except for patients with GBM/ AnaA in the Expansion Phase, patients with active CNS malignancy are excluded. Asymptomatic small lesions are not considered active. Treated lesions may be considered inactive if they are stable for at least 3 months.
  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: NCT01607905

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

Locations
United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact    888-663-3488      
Principal Investigator: Amit Mahipal         
United States, Michigan
Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact    800-527-6266    info@karmanos.org   
Principal Investigator: Anthony Shields         
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact    212-639-2000      
Principal Investigator: John Gerecitano         
United States, Ohio
Gabrail Cancer Center Recruiting
Canton, Ohio, United States, 44718
Contact    330-492-3345      
Principal Investigator: Nashat Gabrail         
Canada, Ontario
Princess Margaret Hospital Recruiting
Toronto, Ontario, Canada, M5T 2M9
Contact    416 946 2000      
Principal Investigator: Albiruni Razak         
Denmark
Rigshospitalet Recruiting
Copenhagen, Denmark, 2100
Contact    +45 3545 3545      
Principal Investigator: Morten Mau-Sørensen         
Sponsors and Collaborators
Karyopharm Therapeutics, Inc
  More Information

No publications provided

Responsible Party: Karyopharm Therapeutics, Inc
ClinicalTrials.gov Identifier: NCT01607905     History of Changes
Other Study ID Numbers: KCP-330-002
Study First Received: May 16, 2012
Last Updated: January 13, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Karyopharm Therapeutics, Inc:
Selinexor
KPT-330
Squamous Cell Carcinoma
Glioblastoma multiforme
Adenocarcinoma
Melanoma

ClinicalTrials.gov processed this record on March 01, 2015