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 December 2013 by NPM Pharma Inc.
Sponsor:
Information provided by (Responsible Party):
NPM Pharma Inc.
ClinicalTrials.gov Identifier:
NCT01607905
First received: May 16, 2012
Last updated: December 17, 2013
Last verified: December 2013
  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) KPT- 330 in Patients With Advanced or Metastatic Solid Tumor Malignancies

Resource links provided by NLM:


Further study details as provided by NPM Pharma 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: 90
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.


  Eligibility

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

Inclusions Criteria:

  1. Written informed consent in accordance with federal, local, and institutional guidelines
  2. Age ≥18 years
  3. 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.
  4. 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.

  5. Except for patients with GBM/AnaA in the Expansion Phase Eastern Cooperative Oncology Group (ECOG)Performance Status of 0 1 (Appendix 1). For patients with GBM/ AnaA in the Expansion Phase Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 2 (Appendix 1).
  6. Adequate hematopoietic function: total white blood cell (WBC) count ≥3000/mm3, absolute neutrophil count (ANC) ≥1500/mm3, and platelet count ≥100,000/mm3.
  7. Adequate hepatic function: bilirubin <2 times the upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of < 3 times ULN) and alanine aminotransferase (ALT) <2.5 times ULN. In the case of known (radiological and/or biopsy documented) liver metastasis, ALT <5.0 times ULN is acceptable;
  8. Adequate renal function: estimated creatinine clearance of ≥ 30 mL/min, calculated using the formula of Cockcroft 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.
  10. For GBM/AnaA patients only: up to 100mg prednisone daily dose is acceptable to enroll in this study.

Exclusions Criteria:

  1. Patients who are pregnant or lactating;
  2. 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;
  3. Major surgery within four weeks before Cycle 1 day 1;
  4. Unstable cardiovascular function:

    • symptomatic ischemia, or
    • uncontrolled clinically significant conduction abnormalities (eg: 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 Cycle 1 Day 1 dose;
  5. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose;
  6. Known to be HIV seropositive;
  7. Known active hepatitis A, B, or C infection; or known to be positive for HCV RNA or HBsAg (HBV surface antigen);
  8. 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.
  9. Patients with significantly diseased or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea.
  10. Grade ≥2 peripheral neuropathy within 14 days prior to Cycle 1 Day 1.
  11. Except for patients with GBM/AnaA in the Expansion Phase: History of seizures, movement disorders or cerebrovascular accident within the past 5 years prior to cycle 1 day 1.
  12. Patients with macular degeneration, uncontrolled glaucoma, or markedly decreased visual acuity
  13. In the opinion of the investigator, patients who are significantly below their ideal body weight.
  14. Serious psychiatric or medical conditions that could interfere with treatment;
  15. Participation in an investigational anti-cancer study within 3 weeks prior to first dose of study drug;
  16. Concurrent therapy with approved or investigational anticancer therapeutic. However, patients on stable doses of androgen ablation therapy may continue this therapy during the study.
  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: Amit Mahipal    813-454-4910    Amit.Mahipal@moffitt.org   
United States, Michigan
Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Anthony Shields       shieldsa@karmanos.org   
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10021
Contact: John Gerecitano    212-639-3748    gerecitj@mskcc.org   
United States, Ohio
Gabrail Cancer Center Recruiting
Canton, Ohio, United States, 44718
Contact: Nashat Gabrail    330-365-2135    ngabrailmd@aol.com   
Canada, Ontario
Princess Margaret Hospital Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Razak Albiruni    647 970 9845    Albiruni.Razak@uhn.ca   
Denmark
Rigshospitalet Recruiting
Copenhagen, Denmark, 2100
Contact: Morten Mau-Sørensen    +45 3545 4396    Morten.Mau-Soerensen@regionh.dk   
Sponsors and Collaborators
NPM Pharma Inc.
  More Information

No publications provided

Responsible Party: NPM Pharma Inc.
ClinicalTrials.gov Identifier: NCT01607905     History of Changes
Other Study ID Numbers: KCP-330-002
Study First Received: May 16, 2012
Last Updated: December 17, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on August 18, 2014