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A First-in-human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of DS-6051b

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ClinicalTrials.gov Identifier: NCT02279433
Recruitment Status : Active, not recruiting
First Posted : October 31, 2014
Last Update Posted : April 3, 2018
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Brief Summary:
DS-6051b is an orally administered inhibitor of the tyrosine kinases (ROS1) and neurotropic tyrosine kinase receptors (NTRK). This phase 1 first-in-human study evaluates safety and tolerability of DS-6051b in cancer subjects and identify a recommended phase 2 dose (RP2D). In addition, this study will also assess the pharmacokinetic (PK)/pharmacodynamic (PD) profiles and preliminary efficacy of DS-6051b.

Condition or disease Intervention/treatment Phase
Solid Tumors Drug: DS6051b Phase 1

Detailed Description:

The Dose Escalation part (Part 1) of this study will evaluate safety and tolerability, and determine the tentative RP2D. Plasma exposure of DS-6051a and the exposure - QT interval prolongation relationship will also be assessed. Approximately 30 subjects with advanced solid tumors harboring ROS1 or NTRK1, NTRK2, or NTRK3 rearrangement, neuroendocrine carcinoma, or with advanced solid tumors and tumor-induced pain will be enrolled.

The Food Effect (FE) part of this study is to determine the effect of food on the PK of DS-6051a following administration of a single oral dose of DS-6051b. The safety and tolerability of DS-6051b administered with or without food will also be assessed.

After the safety profile of DS-6051b is adequately evaluated, the Dose Expansion part (Part 2) will be initiated to further assess the safety and tolerability, and preliminarily evaluate the efficacy of DS-6051b at the tentative RP2D. Approximately 40 cancer subjects carrying a ROS1 or NTRK1, NTRK2, or NTRK3 rearrangement will be enrolled.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Two-Part, Multi-Center, Non Randomized, Open-Label, Multiple Dose First-In-Human Study Of DS-6051b, An Oral ROS1 And NTRK Inhibitor, In Subjects With Advanced Solid Tumors
Study Start Date : September 2014
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : November 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: DS-6051b
DS-6051b is orally administered as 50 mg and 200 mg capsules once daily on Days 1 to 21 of a 21-day cycle. Dose escalation in Part 1 will continue until tentative Recommended Part 2 Dose (RP2D) is determined. In Part 2 participants will receive the RP2D.
Drug: DS6051b
DS-6051b 50 mg and 200 mg capsules for oral administration
Other Names:
  • Investigational product
  • DS-6051a (a free base of 6051b)




Primary Outcome Measures :
  1. Part 1: Number of participants with dose-limiting toxicities [ Time Frame: within 21 days following the first dose of treatment ]
  2. Part 2: Tumor response [ Time Frame: up to 2 years ]
    Tumor response will be assessed using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.


Secondary Outcome Measures :
  1. Maximum concentration (Cmax) for DS-6051a [ Time Frame: At Days 1 and 15 of Cycle 1 ]
  2. Time to maximum concentration (Tmax) for DS-6051a [ Time Frame: At Days 1 and 15 of Cycle 1 ]
  3. Area under the concentration-time curve from time zero to t (AUC0-t) for DS-6051a [ Time Frame: At Days 1 and 15 of Cycle 1 ]
  4. Change from baseline in QTc interval [ Time Frame: within 2 years ]
    ECGs performed to assess QTc interval (ms) at baseline and on study treatment and at the end of treatment visit.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically or cytologically confirmed diagnosis of advanced solid tumors that have relapsed from or are refractory to standard treatment or for which no standard treatment is available
  2. Part 1 Dose Escalation subjects must meet 1 of the following criteria:

    • Solid tumors with documented ROS1, NTRK1, NTRK2, or NTRK3 rearrangement
    • Neuroendocrine tumors
    • Solid tumors with tumor-induced pain
  3. Part 2 Dose Expansion subjects must meet 1 of the following criteria:

    • NSCLC with documented ROS1, NTRK1, NTRK2, or NTRK3 rearrangement
    • k-RAS wild-type CRC with documented NTRK1, NTRK2, or NTRK3 rearrangement
    • Other solid tumors with documented ROS1, NTRK1, NTRK2, or NTRK3 rearrangement
    • Pulmonary LCNEC;
  4. Male or female ≥18 years of age
  5. Eastern Cooperative Oncology Group performance status 0 to 1
  6. Adequate organ function
  7. Adequate blood clotting function
  8. Women of childbearing potential must have a negative pregnancy test
  9. Willingness to provide archival tumor samples
  10. Other inclusion criteria may apply

Exclusion Criteria:

  1. Hematological malignancies
  2. Known positive HIV infection, or active hepatitis B or C infection
  3. Comorbidity that would interfere with therapy
  4. Receipt of an allogeneic bone marrow or allogeneic stem cell transplant
  5. Concomitant medical condition that would increase the risk of toxicity, in the opinion of the Investigator or Sponsor
  6. History of myocardial infarction and unstable angina within 6 months before study drug treatment; symptomatic congestive heart failure (Congestive Heart Failure New York Heart Association Class III or IV); congenital long QT syndrome; or ventricular arrhythmias defined as grade ≥2 according to NCI CTCAE, v4
  7. Clinically active primary central nervous system tumors or brain metastases with the exception of subjects with glioblastoma multiform that carry ROS1 rearrangement
  8. Unresolved toxicities from previous anticancer therapy
  9. Systemic treatment with anticancer therapy within 3 weeks before study drug treatment
  10. Therapeutic radiation therapy or major surgery within 4 weeks before study drug treatment or palliative radiation therapy within 2 weeks before study drug treatment
  11. Participation in a therapeutic clinical study within 3 weeks for biological treatments, and within 2 weeks or 5 half-lives, whichever is longer, for small molecule agents, before study drug treatment
  12. Concomitant treatment with strong inhibitors or inducers of CYP3A4 and P-glycoprotein
  13. Clinically significant malabsorption syndrome or other gastrointestinal disease that would impact drug absorption
  14. QTcF values higher than 450 ms at screening
  15. Breastfeeding
  16. Other exclusion criteria may apply

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02279433


Locations
United States, Arizona
HonorHealth Research Institute
Scottsdale, Arizona, United States, 85258
United States, California
Chao Family Comprehensive Cancer Center of
Orange, California, United States, 92868
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana Farber Cancer Inst.
Boston, Massachusetts, United States, 02215
United States, New York
New York University
New York, New York, United States, 10016
United States, Texas
South Texas Accelerated Research Therapeutics
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Daiichi Sankyo, Inc.
Investigators
Study Director: Global Clinical Leader Daiichi Sankyo, Inc.

Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT02279433     History of Changes
Other Study ID Numbers: DS6051-A-U101
First Posted: October 31, 2014    Key Record Dates
Last Update Posted: April 3, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at http://www.clinicalstudydatarequest.com. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://www.clinicalstudydatarequest.com/Study-Sponsors-DS-Details.aspx
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Studies for which the medicine and indication have received EU and US marketing approval on or after 01 January 2014 or by the US or EU Health Authorities when regulatory submissions in both regions are not planned and after the primary study results have been accepted for publication.
Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States and the European Union from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
URL: https://www.clinicalstudydatarequest.com/Study-Sponsors-DS-Details.aspx

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Daiichi Sankyo, Inc.:
Neoplasms
Lung Neoplasms
Colorectal Neoplasms
Neuroendocrine Tumors
Pancreatic Neoplasms