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DS-1205c With Gefitinib for Metastatic or Unresectable Epidermal Growth Factor Receptor (EGFR)-Mutant Non-Small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT03599518
Recruitment Status : Completed
First Posted : July 26, 2018
Last Update Posted : July 7, 2020
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )

Tracking Information
First Submitted Date  ICMJE July 16, 2018
First Posted Date  ICMJE July 26, 2018
Last Update Posted Date July 7, 2020
Actual Study Start Date  ICMJE October 9, 2018
Actual Primary Completion Date April 22, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 16, 2018)
  • Number pf participants with dose-limiting toxicities during the Dose Escalation period [ Time Frame: within 28 days ]
  • Number of participants with adverse events (AEs) [ Time Frame: within 36 months ]
    An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 16, 2018)
  • Plasma concentration of DS-1205a versus time [ Time Frame: during the 7 day run-in period ]
  • Maximum observed analyte concentration (Cmax) [ Time Frame: during the 7 day run-in period ]
  • Actual sampling time to reach Cmax (Tmax) [ Time Frame: during the 7 day run-in period ]
  • Area under the analyte concentration versus time curve during a dosing interval (AUCtau) [ Time Frame: during the 7 day run-in period ]
  • Minimum observed analyte concentration prior to the beginning, or at the end, of a dosing interval (Ctrough) [ Time Frame: during the 7 day run-in period ]
  • Cmax during a dosing interval (Tau) at steady state (Cmax,ss) [ Time Frame: during the dose expansion period, within 36 months ]
    Categories: DS-1205a, gefitinib
  • Plasma concentration of DS-1205a versus time [ Time Frame: during the dose expansion period, within 36 months ]
    Categories: DS-1205a, gefitinib
  • Tmax [ Time Frame: during the dose expansion period, within 36 months ]
    Categories: DS-1205a, gefitinib
  • Ctrough [ Time Frame: during the dose expansion period, within 36 months ]
    Categories: DS-1205a, gefitinib
  • AUCtau [ Time Frame: during the dose expansion period, within 36 months ]
    Categories: DS-1205a, gefitinib
  • Objective response rate (ORR), graded according to RECIST version 1.1 [ Time Frame: within 36 months ]
    Objective response rate is calculated as the number of participants with best objective response [complete response (CR) or partial response (PR) determined by Investigator assessment based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1], divided by the number of participants in the analysis population.
  • Change from baseline in size of target lesion(s) [ Time Frame: within 36 months ]
  • Duration of response (DOR) [ Time Frame: within 36 months ]
    DOR is defined as the time from documentation of tumor response [either CR or PR] to disease progression
  • Disease control rate (DCR) [ Time Frame: within 36 months ]
    DCR is defined as the sum of CR rate, PR rate, and stable disease (SD) rate
  • Progression-free survival (PFS) [ Time Frame: within 36 months ]
    PFS is defined as the time from the date of the first dose to the earlier of the dates of the first objective documentation of radiographic PD, or death due to any cause
  • Overall survival (OS) [ Time Frame: within 36 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE DS-1205c With Gefitinib for Metastatic or Unresectable Epidermal Growth Factor Receptor (EGFR)-Mutant Non-Small Cell Lung Cancer
Official Title  ICMJE A Multicenter, Open-Label Phase 1 Study of DS-1205c in Combination With Gefitinib in Subjects With Metastatic or Unresectable EGFR-Mutant Non-Small Cell Lung Cancer
Brief Summary

This study has two parts: dose escalation and dose expansion.

The primary objectives are:

  • For Dose Escalation, to assess the safety and tolerability of DS-1205c when combined with gefitinib in the study population and to determine the recommended dose for expansion of DS-1205c when combined with gefitinib in the study population
  • For Dose Expansion, to assess the safety and tolerability of DS-1205c when combined with gefitinib in the study population.

In Dose Escalation, after a 7-day run in period (Cycle 0), there will be 21-day cycles (Cycle 1 onward). In Dose Expansion, there will be 21-day cycles.

The number of treatment cycles is not fixed in this study. Participants will continue study treatment for 36 months unless they decide not to (withdraw consent), their disease gets worse [progressive disease (PD)], or side effects become unacceptable (unacceptable toxicity).

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non Small Cell Lung Cancer
Intervention  ICMJE
  • Drug: DS-1205c
    DS-1205c 200 mg capsule for oral administration
    Other Name: Experimental product
  • Drug: Gefitinib
    Gefitinib 250 mg tablet for oral administration
Study Arms  ICMJE Experimental: DS-1205c with Gefitinib
Participants receive DS-1205c (at planned doses given orally twice daily: 200 mg, 400 mg, 600 mg, 800 mg) in combination with daily 250 mg oral dose of gefitinib
Interventions:
  • Drug: DS-1205c
  • Drug: Gefitinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 3, 2020)
21
Original Estimated Enrollment  ICMJE
 (submitted: July 16, 2018)
63
Actual Study Completion Date  ICMJE June 29, 2020
Actual Primary Completion Date April 22, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Has histologically or cytologically documented adenocarcinoma NSCLC
  2. Has locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation
  3. Has acquired resistance to EGFR tyrosine kinase inhibitor (TKI) according to the Jackman criteria (PMID: 19949011):

    1. Historical confirmation that the tumor harbors an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q) OR
    2. Has experienced clinical benefit from an EGFR TKI, followed by systemic progression [Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) or World Health Organization (WHO)] while on continuous treatment with an EGFR TKI
  4. Is currently receiving and able to interrupt gefitinib or discontinue erlotinib, afatinib, or osimertinib
  5. Has been receiving gefitinib, erlotinib, afatinib, or osimertinib for at least 6 weeks with well-controlled related toxicities less than Grade 3 in severity at the time of screening period; participants who have been receiving gefitinib must be taking gefitinib at a dose of 250 mg/day
  6. Has radiological documentation of disease progression while receiving continuous treatment with gefitinib, erlotinib, afatinib, or osimertinib
  7. Has at least one measurable lesion per RECIST version 1.1
  8. Is willing to provide archival tumor tissue from a biopsy performed after progression during treatment with gefitinib, erlotinib, afatinib, or osimertinib OR has at least one lesion, not previously irradiated, amenable to core biopsy and is willing to undergo screening tumor biopsy
  9. Demonstrates absence of EGFR T790M mutation in tumor tissue since progression during gefitinib, erlotinib, afatinib, or osimertinib treatment
  10. Has Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1, with no deterioration over the previous 2 weeks

Exclusion Criteria:

  1. Has any evidence of small cell histology, or combined small cell and non-small cell histology, in original tumor biopsy or in screening biopsy performed since progression
  2. Has previously documented evidence of anaplastic lymphoma kinase (ALK) fusion, ROS proto-oncogene 1 (ROS1) fusion, BRAF V600E mutation, rearranged during transfection (RET) rearrangement, human epidermal growth factor receptor 2 (HER2) mutation, or MET exon 14 skipping mutation - no new testing for these genomic alterations is required for Screening
  3. Has received treatment with any of the following:

    1. Any cytotoxic chemotherapy, immune checkpoint inhibitor therapy, investigational agent or other anticancer drug(s) from a previous cancer treatment regimen or clinical study (other than EGFR TKI), within 14 days of the first dose of study treatment
    2. Immune checkpoint inhibitor therapy within 30 days of first dose of study treatment
    3. Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study treatment
    4. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks, or palliative radiation therapy within 2 weeks of the first dose of study drug treatment
  4. Has history of other active malignancy within 3 years prior to enrollment, except:

    1. Adequately treated non-melanoma skin cancer OR
    2. Superficial bladder tumors (Tumor stage "a" [Ta], Tumor stage "is" [Tis], Tumor stage "1" [T1]) OR
    3. Curatively treated in situ disease OR
    4. Low-risk non-metastatic prostate cancer (with Gleason score < 7 on antiandrogen therapy)
  5. Has spinal cord compression or clinically active brain metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms - Subjects with clinically inactive brain metastases may be included in the study. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment (1 week for stereotactic radiotherapy).
  6. Has retinal disease in the eye that is not due to neovascular age-related macular degeneration (nAMD; eg, significant diabetic retinopathy, glaucomatous retinal atrophy, retinal detachment)
  7. Has history of myocardial infarction within the past 6 months
  8. Has symptomatic congestive heart failure [New York Heart Association (NYHA) Classes II-IV], unstable angina, or cardiac arrhythmia requiring antiarrhythmic treatment
  9. Has left ventricular ejection fraction (LVEF) < 45% by either echocardiogram (ECHO) or multigated acquisition (MUGA) scan
  10. Has any clinically important abnormalities in rhythm, conduction or morphology of resting ECG, eg, complete left bundle branch block, third-degree heart block, second-degree heart block, or PR interval > 250 milliseconds (ms)
  11. Has a mean corrected QT interval using Fridericia's correction (QTcF) prolongation >470 ms for females and >450 ms for males in three successive Screening measurements
  12. Unable or unwilling to discontinue concomitant use of drugs that are known to prolong the QT interval
  13. Has any factors that increase the risk of QTc prolongation or risk of arrhythmic events, such as congenital long QT. syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives
  14. Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required corticosteroid treatment, has current ILD/pneumonitis, or has suspected ILD/pneumonitis which cannot be ruled out by imaging at screening
  15. Has history of pancreatitis within the past 6 months
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03599518
Other Study ID Numbers  ICMJE DS1205-A-J102
184026 ( Registry Identifier: JAPIC CTI )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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 https://vivli.org/. 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://vivli.org/ourmember/daiichi-sankyo/
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all 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, the European Union and/or Japan 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://vivli.org/ourmember/daiichi-sankyo/
Responsible Party Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )
Study Sponsor  ICMJE Daiichi Sankyo Co., Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Study Leader Daiichi Sankyo, Inc.
PRS Account Daiichi Sankyo, Inc.
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP