Clinical trial NCT01284192: Study of an Investigational Drug, ASP3026, in Patients With Advanced Malignancies (Solid Tumors and B-Cell Lymphoma)
Official title: A Phase 1, Multicenter, Open-Label, Dose Escalation Study of ASP3026 in Subjects With Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Malignancies
Positive for Anaplastic Lymphoma Kinase
Positive for Proto-Oncogene Tyrosine-Protein Kinase ROS
Solid Tumor
B-Cell Lymphoma
Keywords: B-cell Lymphoma
Advanced Malignancies
Anaplastic Lymphoma Kinase (ALK)
ASP3026
Solid Tumor
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2011-01-26
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety and tolerability of ASP3026 assessed by recording of adverse events, laboratory assessments, vital signs, electrocardiograms (ECGs) and clinical observations
timeFrame: Up to 30 days after last subject discontinues treatment
Secondary outcomes:
measure: Pharmacokinetic assessment through analysis of blood and urine samples
timeFrame: Up to Day 29
measure: Objective response rate (ORR)
timeFrame: 30 Days after the last subject discontinues treatment
Other outcomes:
Locations:
city: Orange
country: United States
facility: Site US160
state: California
city: Sacramento
country: United States
facility: Site US184
state: California
city: Chicago
country: United States
facility: Site US11
state: Illinois
city: Detroit
country: United States
facility: Site US2688
state: Michigan
city: Houston
country: United States
facility: Site US2492
state: Texas
city: San Antonio
country: United States
facility: Site US1905
state: Texas
Study officials:
affiliation: Astellas Pharma Global Development
name: Senior Medical Director
role: STUDY_DIRECTOR
References:
citation: Li T, LoRusso P, Maitland ML, Ou SH, Bahceci E, Ball HA, Park JW, Yuen G, Tolcher A. First-in-human, open-label dose-escalation and dose-expansion study of the safety, pharmacokinetics, and antitumor effects of an oral ALK inhibitor ASP3026 in patients with advanced solid tumors. J Hematol Oncol. 2016 Mar 10;9:23. doi: 10.1186/s13045-016-0254-5.