Lung Cancer, Nonsmall Cell
Conditions
Brief 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.
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.
Interventions
DRUGCrizotinib
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.
Sponsors
Pfizer
University of Colorado, Denver
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. Stage IA-IIIA NSCLC by 8th edition AJCC staging (that is deemed to be surgically resectable by a board certified thoracic surgeon. 2. 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) 3. 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. 4. Measurable disease defined by RECIST 1.1 criteria. 5. Life expectancy of at least 24 months. 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 7. Age ≥ 18 years 8. Have normal QT interval on ECG evaluation QT corrected Fridericia (QTcF) of ≤ 450 ms in males or ≤ 470 ms in females 9. 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 10. Negative serum pregnancy test within 7 days of D1 of treatment in women of child bearing potential. 11. 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. 12. Ability to provide signed informed consent and willing and able to comply with all study requirements.
Exclusion criteria
1. Stage IIIB or IV NSCLC. 2. History or the presence of pulmonary interstitial disease, or drug-related pneumonitis. 3. Malabsorption syndrome or other GI illness that could affect oral absorption of the study drug 4. Inability to swallow oral medications 5. Have significant, uncontrolled or active cardiovascular disease, specifically including but restricted to: * Myocardial infarction (MI) within 6 months of trial enrollment * 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 6. Have active infection requiring antibiotics 7. Pregnant or lactating female. 8. Prior treatment with an ALK, ROS1 or MET inhibitor 9. Any prior anticancer therapy for this diagnosis 10. 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. 11. 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants With an Objective Tumor Response Rate | 6 weeks | Participants' tumor response to treatment will be compared from initial/pretreatment scan to 6 week scan using RECIST 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants With Pathologic Response Rate | 37 months | Pathologic response rate is defined as \< 50% of viable tumor present histologically in the resected tumor specimen. |
| Number of Participants With an Objective Response Rate | 6 weeks post treatment | Number of participants with response rate per RECIST 1.1 |
| The Number of Participants With Disease-free Survival (DFS) | 37 months | DFS is defined as the time from treatment to the first of either disease recurrence or death from any cause. |
| Overall Survival (OS) Measured in Months | 37 months | OS is defined as the time from study enrollment to death from any cause. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Neoadjuvant Treatment With Crizotinib 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.
Crizotinib: 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. | 3 |
| Total | 3 |
Baseline characteristics
| Characteristic | Neoadjuvant Treatment With Crizotinib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Age, Continuous | 62 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 3 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 3 |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
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
Time frame: 6 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Neoadjuvant Treatment With Crizotinib | The Number of Participants With an Objective Tumor Response Rate | 3 participants |
Secondary
Number of Participants With an Objective Response Rate
Number of participants with response rate per RECIST 1.1
Time frame: 6 weeks post treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Neoadjuvant Treatment With Crizotinib | Number of Participants With an Objective Response Rate | 0 participants |
Secondary
Overall Survival (OS) Measured in Months
OS is defined as the time from study enrollment to death from any cause.
Time frame: 37 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Neoadjuvant Treatment With Crizotinib | Overall Survival (OS) Measured in Months | 37 months |
Secondary
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.
Time frame: 37 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Neoadjuvant Treatment With Crizotinib | The Number of Participants With Disease-free Survival (DFS) | 0 Participants |
Secondary
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.
Time frame: 37 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Neoadjuvant Treatment With Crizotinib | The Number of Participants With Pathologic Response Rate | 0 Participants |
Comparison: Three subjects enrolled. No statistical analysis completed due to low accrual.