Clinical trial NCT01705483: A Phase 1, Dose Escalation Study to Assess the Safety and Tolerability of ASP9853 With Either Docetaxel or Paclitaxel in Patients With Advanced Non-hematologic Malignancies
Official title: A Phase 1, Multicenter, Open-Label, Dose Escalation Study of ASP9853 in Combination With Either Docetaxel or Paclitaxel in Subjects With Advanced Non-hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Pharmacokinetics of ASP9853
Non-hematologic Malignancies
Keywords: ASP9853
Docetaxel
Paclitaxel
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2012-10-12
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: The purpose of this study is to determine the safety and tolerability and pharmacokinetics of ASP9853 combined with docetaxel or with paclitaxel in subjects with advanced non-hematologic malignancies.

Detailed description: This is a two part study. Part 1 will test increasing dose levels of ASP9853 in combination with docetaxel. Part 2 will test increasing doses of ASP9853 combined with paclitaxel. Each part will determine the maximum tolerated dose and recommended Phase 2 dose for ASP9853 in combination with each taxane. Preliminary evidence of antitumor activity of ASP9853 in combination with docetaxel or with paclitaxel also will be explored.

Eligibility criteria: Inclusion Criteria:

* Subject must have a histologically or cytologically confirmed incurable, locally advanced, or metastatic non-hematologic malignancy that has progressed or failed to respond to regimens or therapies known to provide clinical benefit
* Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
* Subject must have recovered from the effects of prior systemic antineoplastic or radiation therapy(s) to ≤ Grade 1 severity or to subject's baseline values, excluding alopecia
* Subject agrees not to participate in another interventional study while on treatment

Female subject must be either:

Of non child bearing potential:

* post-menopausal (defined as at least 1 year without any menses) prior to Screening or
* documented surgically sterile or status post hysterectomy (at least 1 month prior to Screening)

Or, if of childbearing potential:

* must have a negative serum pregnancy test at Screening and
* must use two forms of birth control (at least one of which must be a barrier method) starting at Screening and throughout the study period and for 28 days after final study drug administration

Acceptable forms include:

* Established use of oral, injected or implanted hormonal methods of contraception.
* Placement of an intrauterine device (IUD) or intrauterine system (IUS).
* Barrier methods of contraception: Condom OR Occlusive cap (diaphragm or cervical/vault caps) with spermicidal
* foam/gel/film/cream/suppository
* Female subject must not donate ova starting at Screening and throughout the study period and for 28 days after final study drug administration.
* Male subject must not donate sperm starting at Screening and throughout the study period and for 28 days after final study drug administration.
* Subject with adequate bone marrow, renal, and hepatic function at baseline

Exclusion Criteria:

* Subject has received more than 3 prior cytotoxic agent-containing regimens
* Subjects with prior anaphylactic or hypersensitivity reaction to prior taxane therapy
* Subject with symptomatic central nervous system (CNS) metastases or leptomeningeal involvement
* Subjects who received treatments with any of the following:

  * Systemic chemotherapy within 21 days
  * Nitrosoureas or mitomycin C within 42 days
  * Radiotherapy to ≥ 25% of hematopoietically active bone marrow within 21 days
* Subject had major surgical procedure within 28 days or anticipates need for major surgical procedure during course of the study
* Female subjects who are breastfeeding at Screening or during the study period and for 28 days after final study drug administration.
* Subject with peripheral neuropathy \> Grade 1 at baseline
* Subject with known hepatitis B surface antigen (HBsAg) positive status; or known or suspected active hepatitis C infection; or known human immunodeficiency virus (HIV) positive
* Subject with malabsorption syndrome or disease or condition significantly affecting gastrointestinal function
* Subject with significant or uncontrolled cardiac, renal, hepatic or other systemic disorders, or significant psychological conditions at baseline
* Subject with clinically significant electrocardiogram (ECG) abnormalities on 12 lead ECG performed within 14 days before start of study drug
* Subject who has received strong inhibitors or inducers of CYP3A4 within two weeks prior to start of study treatment and while on study
* Subject has participated in any interventional clinical study or has been treated with any investigational drugs within 30 days or 5 half lives, whichever is longer, prior to the initiation of Screening

Primary outcomes:
measure: Safety assessed by recording of adverse events, clinical laboratory evaluation, electrocardiograms (ECGs) physical examinations, and vital signs
timeFrame: Duration of study (24 months) to Final Study Visit, up to ≥ 30 days after last dose of ASP9853
Secondary outcomes:
measure: Pharmacokinetics (PK) Profile for ASP9853: AUC24, AUClast, AUCinf, Cmax, Ctrough, tmax, t1/2, CL/F, and Vz/F
timeFrame: Parts 1 and 2, Cycle 1, Day 1: Pre-dose and 9 times within the 24 hour period following ASP9853 dosing; Days 8 and 15: pre-dose, Cycles 2 + , Day 1: predose
measure: Pharmacokinetics (PK) Profile for Docetaxel: AUC24, AUClast, AUCinf, Cmax, tmax, t1/2, CL, and Vd ss
timeFrame: Part 1, Cycle 1, Day 1: Pre-dose and 9 times within the 24 hour period
measure: Pharmacokinetics (PK) Profile for Paclitaxel: AUC24, AUClast, AUCinf, Cmax, tmax, t1/2, CL, and Vd ss
timeFrame: Part 2: Cycle 1: Day 1: Pre-dose and 9 times within the 24 hour period
measure: Objective response rate (ORR)
timeFrame: Treatment start to final Study Visit , up to 24 months
measure: Duration of response (DOR)
timeFrame: CR or PR response until last study visit at which a tumor assessment or an assessment of clinical disease progression is performed, up to 24 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Center
state: Michigan
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
Study officials:
affiliation: Astellas Pharma Global Development
name: Medical Director
role: STUDY_DIRECTOR
References: