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Dacomitinib + Pemetrexed for Patients With Advanced Non-squamous Non-small Cell Lung Cancer (NSCLC)

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ClinicalTrials.gov Identifier: NCT01918761
Recruitment Status : Terminated (poor accrual)
First Posted : August 8, 2013
Results First Posted : December 30, 2019
Last Update Posted : December 30, 2019
Sponsor:
Information provided by (Responsible Party):
Central European Cooperative Oncology Group

Tracking Information
First Submitted Date  ICMJE May 27, 2013
First Posted Date  ICMJE August 8, 2013
Results First Submitted Date  ICMJE November 21, 2019
Results First Posted Date  ICMJE December 30, 2019
Last Update Posted Date December 30, 2019
Study Start Date  ICMJE July 30, 2013
Actual Primary Completion Date September 15, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 12, 2019)
Dose Limiting Toxicities (DLTs) [ Time Frame: From start of treatment to end of treatment or death, whichever occurs first. The study was suspended after 36 months. ]
The primary objective of this study is to determine the maximal tolerated dose (MTD) of the combination pemetrexed + dacomitinib by the incidence of dose limiting toxicities (DLTs).
Original Primary Outcome Measures  ICMJE
 (submitted: August 7, 2013)
Maximal tolerated dose [ Time Frame: 36 month ]
The primary objective of this study is to determine the MTD (maximal tolerated dose) of the combination pemetrexed + dacomitinib by the incidence of DLTs.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 12, 2019)
  • Overall Response Rate [ Time Frame: Until progression of disease (PD) or 24 month after end of treatment for participants with no PD. The study was suspended after 36 months ]
    Overall Response Rate (ORR) is defined as the proportion of patients with complete Response (CR) or partial Response (PR).
  • Overall Survival [ Time Frame: until date of death. The study was suspended after 36 months. ]
    Overall survival (OS) defined as time from start of Dacomitinib to date of death from any cause. Patients without recorded death were censored at the date the patient was last known to be alive. Patients were followed up for survival for 24 month after end of Treatment.
  • Progression-free Survival [ Time Frame: Up to progression or death due to any cause. The study was suspended after 36 months ]
    Progression-free survival (PFS) defined as time from start of Dacomitinib to date of progression or date of death from any cause, whichever occurred first. Patients without recorded progression or death were censored at the last date they were known to have not progressed. Patients were followed up for progression-free survival for 24 month after end of Treatment.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 7, 2013)
MULTIPLE measures - this outcome is a composite !! [ Time Frame: 36 month ]
Overall Response Rate (CR and PR as measured by RECIST) Time to response Duration of response Clinical benefit rate PFS OS Incidence of adverse events and clinical laboratory abnormalities Dacomitinib and pemetrexed PK parameters
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dacomitinib + Pemetrexed for Patients With Advanced Non-squamous Non-small Cell Lung Cancer (NSCLC)
Official Title  ICMJE Dacomitinib + Pemetrexed for Patients With Advanced Non-squamous Non-small Cell Lung Cancer (NSCLC): a Phase I Trial to Identify a Dose of Dacomitinib in Combination With Pemetrexed That is Safe and Tolerated as Determined by the Incidence of Dose Limiting Toxicities (DLTs)
Brief Summary To identify a dose of dacomitinib in combination with pemetrexed that is safe and tolerated as determined by the incidence of DLTs (dose limiting toxicities).
Detailed Description

This open label phase Ib trial aims to determine the safety, tolerability, the pharmacokinetic profile, and to identify a dose of dacomitinib in combination with pemetrexed.

Three sites in Austria will participate in this study. Six to nine patients will initially be enrolled to receive the target dose of 45 mg qd dacomitinib (starting from day 2 of first cycle) in combination with pemetrexed (500 mg/m² 10 min infusion, once every 3 weeks). One cycle is defined as 21 days.

The first 3 subjects will be enrolled at a rate of ≤ 1 subject per week. If the target dose regimen is safe based on the incidence of DLT another 3 subjects will be enrolled.

If the dose of 45 mg qd is not safe alternate lower doses will be explored (dose level -1, dose level -2) to identify the maximal tolerated dose (MTD) of dacomitinib in combination of pemetrexed. Six to nine patients per dose level will be enrolled.

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: Dacomitinib, Pemetrexed
Pemetrexed 500mg/m2 i.v (q21d) Dacomitinib 45mg orally (continuous)
Other Name: Alimta
Study Arms  ICMJE Experimental: Dacomitinib, Pemetrexed
Pemetrexed 500mg/m2 (i.v) q21d Dacomitinib 45mg/ orally (continuous)
Intervention: Drug: Dacomitinib, Pemetrexed
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 Terminated
Actual Enrollment  ICMJE
 (submitted: December 6, 2017)
5
Original Estimated Enrollment  ICMJE
 (submitted: August 7, 2013)
6
Actual Study Completion Date  ICMJE September 15, 2016
Actual Primary Completion Date September 15, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

  • Written informed consent
  • Histologically or cytologically confirmed stage IV non-squamous NSCLC
  • Patients who are candidates to receive pemetrexed monotherapy
  • If pemetrexed has been administered as first line therapy there must be a treatment free interval of at least one cycle (21 days)
  • Measurable disease by RECIST criteria version 1.1.
  • ≥18 years of age
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
  • Adequate left ventricular ejection fraction (LVEF) ≥ 50% by either echocardiogram or multigated acquisition scan (MUGA)
  • Adequate organ function, including:

    1. Adequate bone marrow reserve: absolute neutrophil count (ANC) should be ≥ 1500 cells/mm3, platelets should be ≥ 100.000 cells/mm3
    2. Creatinine clearance ≥ 45 mL/min
    3. Total bilirubin ≤ 1.5 x upper normal limit (ULN)
    4. Aspartate Aminotransferase (AST) (SGOT) ≤ 3 x ULN (≤ 5.0 x ULN if hepatic metastases)
    5. Alanine Aminotransferase (ALT) (SGPT) ≤ 3 x ULN (≤ 5.0 x ULN if hepatic metastases)
  • Female patients or their partners must be postmenopausal (defined as 12 months of amenorrhea following last menses), surgically sterile or must agree to use effective contraception while receiving trial treatment and for at least 3 months thereafter (the definition of effective contraception will be based on the judgment of the investigator). Male patients or their partners must be surgically sterile or must agree to use a barrier method of contraception while receiving trial treatment and for at least 3 months thereafter. (In all cases the definition of effective contraception will be based on the judgment of the investigator).
  • Able to comply with required protocol procedures and able to receive oral medications

Exclusion criteria:

  • Any evidence of mixed histology that includes elements of small cell or carcinoid lung cancer
  • Predominantly squamous cell histology
  • Patients with symptomatic brain metastases
  • Chemotherapy, radiotherapy, biological or investigational agents within two weeks of baseline disease assessments
  • Patients with uncontrolled or significant cardiovascular disease, including:

    1. Myocardial infarction within 12 months
    2. Uncontrolled angina within 6 months
    3. Congestive heart failure within 6 months
    4. Diagnosed or suspected congenital long QT syndrome
    5. Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
    6. Prolonged QTc interval on pre-entry electrocardiogram. QTc must be less than CTC Grade 2 (≤480 msec) using appropriate correction formula with manual read by investigator if required. The echocardiogram (ECG) may be repeated for evaluation of eligibility after management of correctable causes for observed QTc prolongation
    7. Any history of second or third degree heart block (may be eligible if currently have a pacemaker)
    8. Heart rate <50/minute on baseline electrocardiogram
    9. Uncontrolled hypertension
  • Prior malignancy: Patients will not be eligible if they have evidence of other malignancy (other than non-melanoma skin cancer or in situ cervical cancer, or localized and presumed cured prostate cancer with prostate specific antigen (PSA) < ULN) within the last 3 years.
  • Pregnant or lactating females. Serum pregnancy test to be assessed within 7 days prior to study treatment start. Known hypersensitivity to pemetrexed and/or dacomitinib
  • Patients with exposure to other investigational drug therapy
  • Previous therapy with an oral tyrosine kinase inhibitor (TKI)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 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 Austria
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01918761
Other Study ID Numbers  ICMJE CECOG/ NSCLC.1.1.001
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Central European Cooperative Oncology Group
Study Sponsor  ICMJE Central European Cooperative Oncology Group
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Christoph C Zielinski, Univ. Prof. Univ Clinic for Internal Medicine I, Dep of Oncology, Medical University of Vienna
PRS Account Central European Cooperative Oncology Group
Verification Date January 2018

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