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

This study has been terminated.
(Based on the results of the Phase 1 data, the company decided not to pursue the development of this drug at this time.)
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
ClinicalTrials.gov Identifier:
NCT01705483
First received: October 10, 2012
Last updated: July 1, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Pharmacokinetics of ASP9853
Non-hematologic Malignancies
Drug: ASP9853
Drug: Docetaxel
Drug: Paclitaxel
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
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

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Safety assessed by recording of adverse events, clinical laboratory evaluation, electrocardiograms (ECGs) physical examinations, and vital signs [ Time Frame: Duration of study (24 months) to Final Study Visit, up to ≥ 30 days after last dose of ASP9853 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacokinetics (PK) Profile for ASP9853: AUC24, AUClast, AUCinf, Cmax, Ctrough, tmax, t1/2, CL/F, and Vz/F [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Area under the plasma concentration curve at 24 hours (AUC24), AUC from time zero to time of last measurable concentration (AUClast), AUC with the last concentration extrapolated to infinity (AUCinf), Maximum concentration (Cmax), Trough plasma concentration (Ctrough),Time to attain Cmax (Tmax), Apparent terminal elimination half-life (T1/2), Oral clearance (CL/F), and Volume of distribution during the terminal phase (Vz/F)

  • Pharmacokinetics (PK) Profile for Docetaxel: AUC24, AUClast, AUCinf, Cmax, tmax, t1/2, CL, and Vd ss [ Time Frame: Part 1, Cycle 1, Day 1: Pre-dose and 9 times within the 24 hour period ] [ Designated as safety issue: No ]
    Clearance (CL), Distribution volume, steady state (Vd ss)

  • Pharmacokinetics (PK) Profile for Paclitaxel: AUC24, AUClast, AUCinf, Cmax, tmax, t1/2, CL, and Vd ss [ Time Frame: Part 2: Cycle 1: Day 1: Pre-dose and 9 times within the 24 hour period ] [ Designated as safety issue: No ]
  • Objective response rate (ORR) [ Time Frame: Treatment start to final Study Visit , up to 24 months ] [ Designated as safety issue: No ]
    The proportion of subjects with a complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) Criteria Version 1.1

  • Duration of response (DOR) [ Time Frame: 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 ] [ Designated as safety issue: No ]

Enrollment: 21
Study Start Date: August 2012
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1: ASP9853 with docetaxel
2 docetaxel dose levels and starting dose of ASP9853 followed by escalation of ASP9853 with additional dose cohorts
Drug: ASP9853
oral
Drug: Docetaxel
intravenous (IV)
Other Name: Taxotere
Experimental: Part 2: ASP9853 with paclitaxel
Starting dose for ASP9853 determined as one dose level below maximum tolerated dose (MTD) determined in Part 1, 2 paclitaxel dose levels and starting dose of ASP9853 followed by escalation of ASP9853 with additional dose cohorts
Drug: ASP9853
oral
Drug: Paclitaxel
Taxol
Other Name: intravenous (IV)

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01705483

Locations
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Michigan
Barbara Ann Karmanos Cancer Center
Detriot, Michigan, United States, 48201
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Investigators
Study Director: Medical Director Astellas Pharma Global Development
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
ClinicalTrials.gov Identifier: NCT01705483     History of Changes
Other Study ID Numbers: 9853-CL-0101
Study First Received: October 10, 2012
Last Updated: July 1, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Astellas Pharma Inc:
ASP9853
Docetaxel
Paclitaxel

Additional relevant MeSH terms:
Neoplasms
Paclitaxel
Docetaxel
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 24, 2014