Study of an Investigational Drug, ASP3026, in Patients With Advanced Malignancies (Solid Tumors and B-Cell Lymphoma)

Phase 1

Completed

• Conditions: Advanced Malignancies; Positive for Proto-Oncogene Tyrosine-Protein Kinase ROS; B-Cell Lymphoma; Solid Tumor; Positive for Anaplastic Lymphoma Kinase
• Interventions: Drug: ASP3026

• Registration Number: NCT01284192
• Lead Sponsor: Astellas Pharma Inc

Brief Summary

This study is to evaluate the safety and anti-tumor activity of ASP3026 in patients with advanced malignancies (solid tumors and B-cell lymphoma).

Detailed Description

This study will be conducted using a traditional 3 + 3 dose escalation study design. Enrollment of at least 3 subjects is planned for each dosing cohort until the Maximum Tolerated Dose (MTD) is determined. Up to three additional subjects per cohort may be enrolled if each additional subject is known to be positive for Anaplastic Lymphoma Kinase (ALK) or Proto-Oncogene Tyrosine-Protein Kinase ROS (ROS) abnormalities. The decision to expand a cohort or dose escalate will be based on the occurrence of dose limiting toxicities (DLTs) in Cycle 1 that are considered by the Investigator to be related (possibly or probably) to ASP3026. Intra-subject dose escalation will be allowed at the discretion of the investigators. The Safety Data Review Committee may elect to enroll additional subjects in a cohort to further evaluate the dose level. Once the MTD is determined, approximately 20 additional subjects with Anaplastic Lymphoma Kinase (ALK) abnormalities will be enrolled at the Recommended Phase 2 Dose. Each cycle will include 28 days of continuous dosing with ASP3026. Treatment with ASP3026 may continue until one of the discontinuation criteria is met.

Study Timeline

• Study Start: 2010-12
• Study First Submitted: 2011-01-25
• Study First Submitted QC: 2011-01-25
• Study First Posted: 2011-01-26
• Primary Completion: 2014-02
• Study Completion: 2016-03
• Status Verified: 2016-06
• Last Update Submitted: 2016-06-27
• Last Update Posted: 2016-06-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 46

Inclusion Criteria

• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

• Histologically or cytologically confirmed diagnosis of a relapsed/refractory solid tumor or B-cell lymphoma and meets at least 1 of the following criteria:

  • Disease progression despite standard therapies
  • No standard therapies are available or such therapies are not anticipated to result in a durable response
  • Standard therapies are considered unsuitable or have been refused

• Able to take oral medications

• Life expectancy > 12 weeks

• For the expansion cohort of the study, all subjects must be confirmed to be positive for ALK gene abnormalities

• Subjects with stable brain metastasis will be allowed

Exclusion Criteria

• Active central nervous system (CNS) metastases or leptomeningeal involvement as assessed through medical history review and physical examination (dose escalation subjects only)
• Known history of a positive test for hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV)
• Known hereditary or acquired immunodeficiency syndrome or human immunodeficiency virus (HIV) infection
• Cardiac arrhythmias > Grade 1 using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v. 4.03
• Class 3 or 4 New York Heart Association congestive heart failure, acute coronary syndrome, myocardial infarction or cerebrovascular accident within 6 months prior to Cycle 1, Day 1
• Inadequate bone marrow, renal, and/or hepatic function
• Confirmed active peptic ulcer disease or history of gastrointestinal bleeding within the past 3 months
• Known history of long QT syndrome

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ASP3026	ASP3026	Subjects will receive escalated doses of ASP3026 to determine the maximum tolerated dose (MTD)

Primary Outcome Measures

Name	Time	Method
Safety and tolerability of ASP3026 assessed by recording of adverse events, laboratory assessments, vital signs, electrocardiograms (ECGs) and clinical observations	Up to 30 days after last subject discontinues treatment

Secondary Outcome Measures

Name	Time	Method
Objective response rate (ORR)	30 Days after the last subject discontinues treatment	Objective response rate is the proportion of subjects who experience complete response/remission (CR) or partial response/remission (PR)
Pharmacokinetic assessment through analysis of blood and urine samples	Up to Day 29

Trial Locations

Locations (6)

Site US184; 🇺🇸 Sacramento, California, United States

Site US11; 🇺🇸 Chicago, Illinois, United States

Site US2492; 🇺🇸 Houston, Texas, United States

Site US160; 🇺🇸 Orange, California, United States

Site US1905; 🇺🇸 San Antonio, Texas, United States

Site US2688; 🇺🇸 Detroit, Michigan, United States