A Safety Study of Oral ZSTK474 in Patients With Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Zenyaku Kogyo Co., Ltd.
ClinicalTrials.gov Identifier:
NCT01280487
First received: January 18, 2011
Last updated: January 24, 2014
Last verified: January 2014
  Purpose

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary efficacy of daily oral doses of ZSTK474, an oral phosphatidylinositol 3-kinase (PI3K) inhibitor, in subjects with advanced solid malignancies.


Condition Intervention Phase
Neoplasms
Drug: ZSTK474
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 1b, Multi-Center, Open Label, Uncontrolled, Serial Cohort, Dose Escalation Study of the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Daily Oral Doses of ZSTK474 in Subjects With Advanced Solid Malignancies

Resource links provided by NLM:


Further study details as provided by Zenyaku Kogyo Co., Ltd.:

Primary Outcome Measures:
  • Maximum tolerated dose [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics [ Time Frame: 21 days ] [ Designated as safety issue: No ]

Enrollment: 39
Study Start Date: January 2011
Study Completion Date: January 2014
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oral ZSTK474
Daily oral dosing for 21 days per cycle
Drug: ZSTK474
Daily oral dosing for 21 days each cycle

  Eligibility

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

Inclusion Criteria:

  1. Male or females ≥18 years of age;
  2. Histologically-confirmed advanced (metastatic or unresectable) solid tumor - for which available therapy is not effective;
  3. ECOG performance status score of ≤2 and an expected survival of >8 weeks;
  4. Recovered from the toxicities of prior chemotherapy, radiotherapy, and other cancer therapies; all toxicities must be determined to be below Grade 2 (assessed using the NCI CTCAE v4.0).
  5. Adequate blood counts with a hemoglobin (Hgb) of ≥9.0 mg/dL, absolute neutrophil count (ANC) >1,500/mm3, and platelets ≥100,000/mm3 (all without transfusion support);
  6. Subjects who are willing and able to provide written informed consent.

In the expanded cohort at the MTD only: Subjects must be willing to undergo mandatory biopsies of tumor tissue twice during the first cycle (before and during dosing) and must have tumor tissue in a location accessible to incisional biopsy of a superficial lesion or percutaneous core needle biopsy on an outpatient basis without undue risk to the subject.

Exclusion Criteria:

  1. Women who are pregnant or breastfeeding;
  2. Men or women of reproductive potential who are not willing to use acceptable means of contraception while on study drug and for an additional 90 days after the last dose of study drug;
  3. Body Mass Index (BMI) is ≥30 kg/m2;
  4. Have primary central nervous system (CNS) tumors or untreated/uncontrolled CNS metastases; Note: Subjects with stable/controlled CNS metastases may be enrolled (i.e., if CNS lesions have been stable in size for at least one month and the subject is off steroid and anti-convulsants).
  5. Have received any investigational interventional agents within the 4 weeks prior to the start of dosing with ZSTK474;
  6. Are receiving concurrent anti-tumor chemotherapy, radiotherapy, or immunotherapy - or have received any of these non-investigational agents within the previous 4 weeks or 5-half-lives (whichever is longer) prior to the start of dosing with ZSTK474;
  7. Are not able or willing to comply with the study procedures, including the study visit schedule;
  8. Have previously been treated with a phosphatidylinositol 3 kinase (PI3K) inhibitor;
  9. Have serious or significant intercurrent illnesses or underlying diseases, such as:

    1. Diabetes
    2. Gastrointestinal disorder
    3. Hepatic: AST or ALT >2.5 x ULN (or >5.0 x ULN with liver metastases) or serum bilirubin >1.5 x ULN;
    4. Renal (acute or chronic renal disease or eGFR <55 mL/min)
    5. Cardiovascular:

      • Uncontrolled hypertension or blood pressure >140/90 mmHg;
      • Symptomatic congestive heart failure;
      • Myocardial infarction within the past 6 months;
      • Unstable angina pectoris;
      • Cardiac arrhythmia;
      • Congenital long QT syndrome;
      • QTc >450 msec for men or >470 msec for women.
    6. Other:

      • Known diagnosis of HIV infection;
      • Other ongoing or active infections;
      • Psychiatric illness, substance abuse or social situation that would preclude study compliance.
      • Other serious concurrent illness that would preclude assessment of drug effect;
      • PT/PTT)/APTT/INR >ULN for subjects not on anti-coagulants; INR > 1.5 x ULN for subjects on low dose warfarin.
  10. Current treatment with the following drugs:

    • any anti-seizure medications;
    • therapeutic anti-coagulant doses of warfarin.
  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: NCT01280487

Locations
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States
United States, Missouri
Washington University
St Louis, Missouri, United States
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
Sponsors and Collaborators
Zenyaku Kogyo Co., Ltd.
Investigators
Principal Investigator: Craig Lockhart, MD Washington University School of Medicine
Principal Investigator: Anthony Olszanski, MD Fox Chase Cancer Center
Principal Investigator: Geoffrey Shapiro, MD PhD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Zenyaku Kogyo Co., Ltd.
ClinicalTrials.gov Identifier: NCT01280487     History of Changes
Other Study ID Numbers: ZSTK474-101
Study First Received: January 18, 2011
Last Updated: January 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Zenyaku Kogyo Co., Ltd.:
ZSTK474
PI3K inhibitor

ClinicalTrials.gov processed this record on September 16, 2014