A Safety Study of Oral ZSTK474 in Patients With Cancer

NCT01280487 | Completed Phase 1 DMC

• 1 other identifier: ZSTK474-101
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 3

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

Keywords

ZSTK474; PI3K inhibitor

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose

  21 days

Secondary Outcomes (1)

• Pharmacokinetics

  21 days

Study Arms (1)

Oral ZSTK474

EXPERIMENTAL

Daily oral dosing for 21 days per cycle

Drug: ZSTK474

Interventions

ZSTK474 DRUG

Daily oral dosing for 21 days each cycle

Oral ZSTK474

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or females ≥18 years of age;
• Histologically-confirmed advanced (metastatic or unresectable) solid tumor - for which available therapy is not effective;
• ECOG performance status score of ≤2 and an expected survival of \>8 weeks;
• 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).
• 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);
• 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.

You may not qualify if:

• Women who are pregnant or breastfeeding;
• 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;
• Body Mass Index (BMI) is ≥30 kg/m2;
• 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).
• Have received any investigational interventional agents within the 4 weeks prior to the start of dosing with ZSTK474;
• 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;
• Are not able or willing to comply with the study procedures, including the study visit schedule;
• Have previously been treated with a phosphatidylinositol 3 kinase (PI3K) inhibitor;
• Have serious or significant intercurrent illnesses or underlying diseases, such as:
• Diabetes
• Gastrointestinal disorder
• Hepatic: AST or ALT \>2.5 x ULN (or \>5.0 x ULN with liver metastases) or serum bilirubin \>1.5 x ULN;
• Renal (acute or chronic renal disease or eGFR \<55 mL/min)
• Cardiovascular:
• Uncontrolled hypertension or blood pressure \>140/90 mmHg;

Sponsors & Collaborators

• Zenyaku Kogyo Co., Ltd.: lead

Study Sites (3)

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Location

Washington University

St Louis, Missouri, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

ZSTK474

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2011
• First Posted: January 20, 2011
• Study Start: January 1, 2011
• Primary Completion: December 1, 2013
• Study Completion: January 1, 2014
• Last Updated: January 16, 2015

Record last verified: 2015-01

Locations

US (3)