A Safety Study of Oral ZSTK474 in Patients With Cancer

Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01280487
• Other study ID #: ZSTK474-101
• Status: Completed
• Phase: Phase 1
• First received: January 18, 2011
• Last updated: January 15, 2015
• Start date: January 2011
• Est. completion date: January 2014

Study information

• Verified date: January 2015
• Source: Zenyaku Kogyo Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: January 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• ZSTK474
Daily oral dosing for 21 days each cycle

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Washington University	St Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Zenyaku Kogyo Co., Ltd.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose		21 days	Yes
Secondary	Pharmacokinetics		21 days	No