A Safety Study of Oral ZSTK474 in Patients With Cancer

NCT ID: NCT01280487

Last Updated: 2015-01-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-31
• Study Completion Date: 2014-01-31

Brief Summary

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.

Conditions

Neoplasms

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Oral ZSTK474

Daily oral dosing for 21 days per cycle

Group Type: EXPERIMENTAL

ZSTK474

Intervention Type: DRUG

Daily oral dosing for 21 days each cycle

Interventions

ZSTK474

Daily oral dosing for 21 days each cycle

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Zenyaku Kogyo Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Craig Lockhart, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Anthony Olszanski, MD

Role: PRINCIPAL_INVESTIGATOR

Fox Chase Cancer Center

Geoffrey Shapiro, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Washington University

St Louis, Missouri, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

ZSTK474-101

Identifier Type: -

Identifier Source: org_study_id