Lung Cancer, Nonsmall CellPhase 2NCT03088930
Evaluating Crizotinib in the Neoadjuvant Setting in Patients With Non-small Cell Lung Cancer
A Phase 2 study testing Crizotinib in people with Lung Cancer, Nonsmall Cell, run by University of Colorado, Denver at 1 site in United States.
Trial summary
This study will evaluate the efficacy of crizotinib as induction therapy in participants with surgically resectable ALK rearrangement, ROS1 rearrangement, or MET exon 14 mutation positive NSCLC. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Lung Cancer, Nonsmall Cell
- What is being tested?
- Crizotinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Dec 2017to 13 Jan 2021
- Phase
- Phase 2
- 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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Stage IA-IIIA NSCLC by 8th edition AJCC staging (that is deemed to be surgically resectable by a board certified thoracic surgeon.
- Staging by PET-CT scan and MRI brain showing no evidence of metastatic disease (mediastinoscopy is not required unless imaging is indeterminate and is then considered standard of care)
- Documented evidence of an ALK rearrangement (by FISH, IHC, or NGS), ROS1 rearrangement (by FISH or NGS), or MET oncogene as defined by MET exon 14 skipping (NGS), MET Y1003X mutation or MET gene fusion (NGS) in NSCLC tumor specimen by a CLIA-approved laboratory.
- Measurable disease defined by RECIST 1.1 criteria.
- Life expectancy of at least 24 months.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Show all 19Show fewer
- Age ≥ 18 years
- Have normal QT interval on ECG evaluation QT corrected Fridericia (QTcF) of ≤ 450 ms in males or ≤ 470 ms in females
- Adequate organ function:
- Absolute neutrophil count (ANC) ≥1500/µL
- Platelets ≥75,000/µL
- Hemoglobin ≥ 10g/dL
- AST /ALT ≤ 2.5 x upper limit of normal (ULN)
- Total serum bilirubin ≤ 1.5 x ULN
- Serum creatinine ≤ 1.5 x UNL
- Serum amylase/lipase ≤ 1.5 x UNL
- Negative serum pregnancy test within 7 days of D1 of treatment in women of child bearing potential.
- If fertile, willing to use highly effective form of contraception (defined as a combination of at least two of the following methods: condom or other barrier methods, oral contraceptives, implantable contraceptives, intrauterine devices) during the dosing period and for at least 4 months after the dosing period.
- Ability to provide signed informed consent and willing and able to comply with all study requirements.
Who cannot join
- Stage IIIB or IV NSCLC.
- History or the presence of pulmonary interstitial disease, or drug-related pneumonitis.
- Malabsorption syndrome or other GI illness that could affect oral absorption of the study drug
- Inability to swallow oral medications
- Have significant, uncontrolled or active cardiovascular disease, specifically including but restricted to:
- Myocardial infarction (MI) within 6 months of trial enrollment
Show all 18Show fewer
- Unstable angina within 6 months of trial enrollment
- Congestive heart failure (CHF) with 6 months prior to trial enrollment
- Any history of ventricular arrhythmia
- Cerebrovascular accident or transient ischemic attack within 6 months of D1 of treatment
- Clinically significant atrial arrhythmia or severe baseline bradycardia defined as resting heart rate < 50 beat per minute
- Uncontrolled hypertension defined as baseline SBP> 160 and DBP > 100 on 3 separate clinic visits or past history of hypertensive urgency, emergency or encephalopathy
- Have active infection requiring antibiotics
- Pregnant or lactating female.
- Prior treatment with an ALK, ROS1 or MET inhibitor
- Any prior anticancer therapy for this diagnosis
- Any active cancer diagnosis (basal or squamous cell cancers allowed) within the last 5 years for which the patient is receiving active therapy or which is untreated. Any cancer diagnosis within the last 5 years that is considered "treated" and/ or on surveillance may be included in the trial.
- Have any condition or illness that, in the opinion of the investigator would compromise patient safety or interfere with evaluation of the study drug (including but not limited to HIV and HCV)
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Denver
Aurora, Colorado, 80045
About this study
Official title: A Phase II Trial to Evaluate Crizotinib in the Neoadjuvant Setting in Patients With Surgically Resectable, ALK, ROS1, or MET-oncogene Positive Non-small Cell Lung Cancer
This study will evaluate the efficacy of crizotinib as induction therapy in participants with surgically resectable ALK rearrangement, ROS1 rearrangement, or MET exon 14 mutation positive NSCLC.
Read the detailed description
Participants with stage IA-IIIA, surgically resectable lung adenocarcinoma with an activating alteration in ALK, ROS1 or MET will receive neoadjuvant treatment with crizotinib. This neoadjuvant treatment will last 6 weeks and on the last day of dosing of crizotinib, participants will undergo surgical resection, followed by 5 years of follow-up via chart review.
- Conditions
- Lung Cancer, Nonsmall Cell
- Being tested
- Crizotinib
- 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.
CrizotinibDrug
Also called Xalkori
Crizotinib is an oral receptor tyrosine kinase inhibitor of ALK, Hepatocyte Growth Factor Receptor (HGFR, c-Met), and ROS1 (c-ros). Crizotinib will be given as a neoadjuvant therapy before surgical resection. The recommended dose of crizotinib is 250mg orally. Participants on this trial will receive this dose, unless dose modification is necessary.
| Study group | Role | What they receive |
|---|---|---|
| Neoadjuvant treatment with Crizotinib | Experimental | Patients enrolled in this study will be treated with 6 weeks of induction therapy with crizotinib. On the last day of dosing, patients will then undergo surgical resection. 5 years of follow-up will be done via chart review. Receives: Drug: Crizotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Number of Participants With an Objective Tumor Response Rate
Participants' tumor response to treatment will be compared from initial/pretreatment scan to 6 week scan using RECIST 1.1
Measured: 6 weeks
Secondary outcomes (4)
The Number of Participants With Pathologic Response Rate
Pathologic response rate is defined as < 50% of viable tumor present histologically in the resected tumor specimen.
Measured: 37 months
Number of Participants With an Objective Response Rate
Number of participants with response rate per RECIST 1.1
Measured: 6 weeks post treatment
The Number of Participants With Disease-free Survival (DFS)
DFS is defined as the time from treatment to the first of either disease recurrence or death from any cause.
Measured: 37 months
Overall Survival (OS) Measured in Months
OS is defined as the time from study enrollment to death from any cause.
Measured: 37 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2017
- Study start13 Dec 2017
- Primary completion13 Jan 2021
- Study completion13 Jan 2021
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 Lung Cancer, Nonsmall CellStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Sponsor
- Investigators
- Tejas Patil, MD, PhD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03088930
- Sponsor's protocol ID
- 16-2025.cc
- Status last verified
- Jan 2022
- First submitted
- 17 Mar 2017
- Last updated
- 11 Feb 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial to Evaluate Crizotinib in the Neoadjuvant Setting in Patients With Surgically Resectable, ALK, ROS1, or MET-oncogene Positive Non-small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT03088930
- Acronym / sponsor ID
- 16-2025.cc
- Conditions
- Lung Cancer, Nonsmall Cell
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- 13 Dec 2017 (actual)
- Primary completion
- 13 Jan 2021 (actual)
- Study completion
- 13 Jan 2021 (actual)
- First posted
- 23 Mar 2017 (actual)
- Results
- Posted 11 Feb 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the efficacy of crizotinib as induction therapy in participants with surgically resectable ALK rearrangement, ROS1 rearrangement, or MET exon 14 mutation positive NSCLC.
Detailed description
Participants with stage IA-IIIA, surgically resectable lung adenocarcinoma with an activating alteration in ALK, ROS1 or MET will receive neoadjuvant treatment with crizotinib. This neoadjuvant treatment will last 6 weeks and on the last day of dosing of crizotinib, participants will undergo surgical resection, followed by 5 years of follow-up via chart review.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant treatment with Crizotinib | Experimental | Drug: CrizotinibPatients enrolled in this study will be treated with 6 weeks of induction therapy with crizotinib. On the last day of dosing, patients will then undergo surgical resection. 5 years of follow-up will be done via chart review. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Stage IA-IIIA NSCLC by 8th edition AJCC staging (that is deemed to be surgically resectable by a board certified thoracic surgeon.
- Staging by PET-CT scan and MRI brain showing no evidence of metastatic disease (mediastinoscopy is not required unless imaging is indeterminate and is then considered standard of care)
- Documented evidence of an ALK rearrangement (by FISH, IHC, or NGS), ROS1 rearrangement (by FISH or NGS), or MET oncogene as defined by MET exon 14 skipping (NGS), MET Y1003X mutation or MET gene fusion (NGS) in NSCLC tumor specimen by a CLIA-approved laboratory.
- Measurable disease defined by RECIST 1.1 criteria.
- Life expectancy of at least 24 months.
Key exclusion criteria (18 listed)
- Stage IIIB or IV NSCLC.
- History or the presence of pulmonary interstitial disease, or drug-related pneumonitis.
- Malabsorption syndrome or other GI illness that could affect oral absorption of the study drug
- Inability to swallow oral medications
- Have significant, uncontrolled or active cardiovascular disease, specifically including but restricted to:
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 |
|---|---|---|
| CrizotinibAlso: XalkoriCrizotinib is an oral receptor tyrosine kinase inhibitor of ALK, Hepatocyte Growth Factor Receptor (HGFR, c-Met), and ROS1 (c-ros). Crizotinib will be given as a neoadjuvant therapy before surgical resection. The recommended dose of crizotinib is 250mg orally. Participants on this trial will receive this dose, unless dose modification is necessary. | Drug | Neoadjuvant treatment with Crizotinib |
Primary outcome
The Number of Participants With an Objective Tumor Response Rate
Time frame: 6 weeks
Participants' tumor response to treatment will be compared from initial/pretreatment scan to 6 week scan using RECIST 1.1
4 secondary outcomes
The Number of Participants With Pathologic Response Rate
Time frame: 37 months
Number of Participants With an Objective Response Rate
Time frame: 6 weeks post treatment
The Number of Participants With Disease-free Survival (DFS)
Time frame: 37 months
Overall Survival (OS) Measured in Months
Time frame: 37 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Tejas Patil, MD, PhD principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Crizotinib in people with Lung Cancer, Nonsmall Cell, run by University of Colorado, Denver at 1 site in United States.
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 19 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: finished, as of the sponsor's last update on 11 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 11 Feb 2022). 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?
The Number of Participants With an Objective Tumor Response Rate (time frame: 6 weeks). 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 11 Feb 2022.