Non Small Cell Lung CancerPhase 1NCT01918761
Dacomitinib + Pemetrexed for Patients With Advanced Non-squamous Non-small Cell Lung Cancer (NSCLC)
A Phase 1 study testing Dacomitinib, Pemetrexed in people with Non Small Cell Lung Cancer, run by Central European Cooperative Oncology Group at 2 sites in Austria.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer
- What is being tested?
- Dacomitinib, Pemetrexed
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 2 sitesAustria
- Study dates
- 30 Jul 2013to 15 Sep 2016
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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:
- Adequate bone marrow reserve: absolute neutrophil count (ANC) should be ≥ 1500 cells/mm3, platelets should be ≥ 100.000 cells/mm3
- Creatinine clearance ≥ 45 mL/min
- Total bilirubin ≤ 1.5 x upper normal limit (ULN)
- Aspartate Aminotransferase (AST) (SGOT) ≤ 3 x ULN (≤ 5.0 x ULN if hepatic metastases)
- 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
Who cannot join
- 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:
- Myocardial infarction within 12 months
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- Uncontrolled angina within 6 months
- Congestive heart failure within 6 months
- Diagnosed or suspected congenital long QT syndrome
- Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
- 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
- Any history of second or third degree heart block (may be eligible if currently have a pacemaker)
- Heart rate <50/minute on baseline electrocardiogram
- 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)
Trial locations and contacts
2 sites in 1 country.
Austria2 sites
Medizinische Universität Graz Klinische Abteilung für Onkologie
Graz
Universitätsklinik für Innere Medizin I
Innsbruck
About this study
Official title: 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)
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).
Read the 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.
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- Dacomitinib, Pemetrexed
- Keywords
- NSCLC, Stage IV, Pemetrexed, Dacomitinib
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dacomitinib, PemetrexedDrug
Also called Alimta
Pemetrexed 500mg/m2 i.v (q21d) Dacomitinib 45mg orally (continuous)
| Study group | Role | What they receive |
|---|---|---|
| Dacomitinib, Pemetrexed | Experimental | Pemetrexed 500mg/m2 (i.v) q21d Dacomitinib 45mg/ orally (continuous) Receives: Drug: Dacomitinib, Pemetrexed |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicities (DLTs)
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).
Measured: From start of treatment to end of treatment or death, whichever occurs first. The study was suspended after 36 months.
Secondary outcomes (3)
Overall Response Rate
Overall Response Rate (ORR) is defined as the proportion of patients with complete Response (CR) or partial Response (PR).
Measured: 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 Survival
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.
Measured: until date of death. The study was suspended after 36 months.
Progression-free Survival
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.
Measured: Up to progression or death due to any cause. The study was suspended after 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2013 (estimated)
- Study start30 Jul 2013
- Primary completion15 Sep 2016
- Study completion15 Sep 2016
Why it stopped: poor accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Central European Cooperative Oncology Group
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Christoph C Zielinski, Univ. Prof., Principal investigator, Univ Clinic for Internal Medicine I, Dep of Oncology, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01918761
- Sponsor's protocol ID
- CECOG/ NSCLC.1.1.001
- Status last verified
- Jan 2018
- First submitted
- 27 May 2013
- Last updated
- 30 Dec 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT01918761
- Acronym / sponsor ID
- CECOG/ NSCLC.1.1.001
- Conditions
- Non Small Cell Lung Cancer
- Keywords
- NSCLC, Stage IV, Pemetrexed, Dacomitinib
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: poor accrual
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Central European Cooperative Oncology GroupUniversity, hospital or other
- Study start
- 30 Jul 2013
- Primary completion
- 15 Sep 2016 (actual)
- Study completion
- 15 Sep 2016 (actual)
- First posted
- 8 Aug 2013 (estimated)
- Results
- Posted 30 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dacomitinib, Pemetrexed | Experimental | Drug: Dacomitinib, PemetrexedPemetrexed 500mg/m2 (i.v) q21d Dacomitinib 45mg/ orally (continuous) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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.
Key exclusion criteria (18 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dacomitinib, PemetrexedAlso: AlimtaPemetrexed 500mg/m2 i.v (q21d) Dacomitinib 45mg orally (continuous) | Drug | Dacomitinib, Pemetrexed |
Primary outcome
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).
3 secondary outcomes
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 Survival
Time frame: until date of death. The study was suspended after 36 months.
Progression-free Survival
Time frame: Up to progression or death due to any cause. The study was suspended after 36 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christoph C Zielinski, Univ. Prof. principal investigator
Univ Clinic for Internal Medicine I, Dep of Oncology, Medical University of Vienna
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dacomitinib, Pemetrexed in people with Non Small Cell Lung Cancer, run by Central European Cooperative Oncology Group at 2 sites in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 30 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Dec 2019.