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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).
Full 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.
Enrollment
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Volunteers
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:
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:
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)
Primary purpose
Allocation
Interventional model
Masking
5 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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