MET Positive, Recurrent Squamous Cell Lung Carcinoma, Stage IV Squamous Cell Lung Carcinoma AJCC v7
Conditions
Brief summary
This randomized phase II/III compares rilotumumab when given together with erlotinib hydrochloride against erlotinib hydrochloride alone in treating patients with stage IV squamous cell lung cancer that has come back after previous treatment. This is a sub-study that includes all screened patients positive for the met proto-oncogene (MET)/hepatocyte growth factor (HGF) biomarker. HGF can interact with MET and can cause tumor cells to grow more quickly. Rilotumumab may decrease the activity of HGF and may be able to shrink tumors. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving rilotumumab with erlotinib hydrochloride works better than erlotinib hydrochloride alone (standard treatment) in treating squamous cell lung cancer.
Detailed description
PRIMARY OBJECTIVES: I. To evaluate if there is sufficient evidence to continue to the phase III component of S1400E by comparing investigator-assessed progression-free survival (IA-PFS) between rilotumumab plus erlotinib versus erlotinib in patients registered to S1400E. (Phase II) II. To determine if there is both a statistically and clinically-meaningful difference in IA-PFS between patients randomized to receive rilotumumab plus erlotinib versus erlotinib. (Phase III) III. To compare overall survival (OS) in patients randomized to rilotumumab plus erlotinib versus erlotinib. (Phase III) SECONDARY OBJECTIVES: I. To compare response rates (confirmed and unconfirmed, complete and partial responses) among patients randomized to receive rilotumumab plus erlotinib versus erlotinib. (Phase II) II. To evaluate the frequency and severity of toxicities associated with rilotumumab plus erlotinib versus erlotinib. (Phase II) III. To compare the response rates (confirmed and unconfirmed, complete and partial) among patients randomized to receive rilotumumab plus erlotinib versus erlotinib. (Phase III) IV. To evaluate the frequency and severity of toxicities associated with rilotumumab plus erlotinib versus erlotinib. (Phase III) TERTIARY OBJECTIVES: I. To evaluate the treatment arm randomization acceptance rate within each treatment arm of S1400E defined as the percentage of patients randomized to a treatment arm that receive any protocol treatment. II. To identify additional predictive or prognostic tumor/blood biomarkers beyond the chosen biomarker. III. To identify potential resistance biomarkers at disease progression. IV. To establish a tissue/blood repository from patients with refractory squamous cell cancer. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I (CLOSED TO ACCRUAL AND INTERVENTION11/25/2014): Patients receive rilotumumab intravenously (IV) over 60-120 minutes on day 1 and erlotinib hydrochloride orally (PO) daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM II (CLOSED TO ACCRUAL AND INTERVENTION11/25/2014): Patients receive erlotinib hydrochloride PO daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, all patients will be followed until death or 3 years after sub-study registration, whichever occurs first.
Interventions
DRUGErlotinib Hydrochloride
Given PO
OTHERLaboratory Biomarker Analysis
Correlative studies
BIOLOGICALRilotumumab
Given IV
Sponsors
National Cancer Institute (NCI)
SWOG Cancer Research Network
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must meet all SCREENING/PRE-SCREENING and SUB-STUDY REGISTRATION COMMON ELIGIBILITY CRITERIA as specified in S1400: Phase II/III Biomarker-Driven Master Protocol for Previously Treated Squamous Cell Lung Cancer (Lung-Map) * Patients must be assigned to S1400E; S1400E biomarker eligibility defined as C-MET positive is defined as follows: * Analyte: C-MET * Assay: Immunohistochemistry (IHC) * Eligible definition: IHC positive based on Dako MET-IHC pharm DX kit * If randomized to arm I rilotumumab plus erlotinib, patients must be willing to provide blood specimens for anti-rilotumumab anti-body testing * Patients must not have peripheral edema \> grade 1 at the time of sub-study registration * Patients must not have received prior treatment with MET pathway, inhibitors or EGFR inhibitors (e.g., erlotinib) * Patients must have total bilirubin =\< 1.5 x institutional upper limits of normal (IULN) within 28 days prior to sub-study registration * Patients must not have abnormalities of the cornea based on history (e.g., dry eye syndrome, Sjorgren?s syndrome), congenital abnormality (e.g., Fuch?s dystrophy), abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal-Rose), and/or abnormal corneal sensitivity test (Schirmer test or similar tear production test) * Patients must not be taking, nor plan to take while on protocol treatment and for 14 days post the last dose of study treatment, drugs, herbal supplements or foods that are known to be strong/moderate CYP3A4 substrates
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Investigator-assessed Progression-free Survival Between Arms | From date of sub-study registration to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause, assessed up to 18 months since completion of accrual | A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to investigator-assessed progression-free survival, comparing the two treatment arms. |
| Objective Response Rate (Confirmed and Unconfirmed, Complete and Partial) Between Arms | Up to 3 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Frequency and Severity of Toxicities Associated With Investigational Therapy Versus Standard of Care | Up to 3 years |
Other
| Measure | Time frame | Description |
|---|---|---|
| Treatment Arm Randomization Acceptance Rate | Up to 3 years | Monitored by the percentage of patients that receive at least one dose of the treatment they are randomized to. |
Countries
United States
Participant flow
Pre-assignment details
This study was terminated early and thus no manuscript will be forthcoming. Outcomes were not analyzed.
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Rilotumumab, Erlotinib) Patients receive rilotumumab IV over 60-120 minutes on day 1 and erlotinib hydrochloride PO daily. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. (CLOSED TO ACCRUAL AND INTERVENTION 11/25/2014)
Erlotinib Hydrochloride: Given PO
Laboratory Biomarker Analysis: Correlative studies
Rilotumumab: Given IV | 3 |
| Arm II (Erlotinib) Patients receive erlotinib hydrochloride PO daily. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. (CLOSED TO ACCRUAL AND INTERVENTION 11/25/2014)
Erlotinib Hydrochloride: Given PO
Laboratory Biomarker Analysis: Correlative studies | 5 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Ineligible | 1 | 0 |
| Overall Study | Not protocol specified | 1 | 0 |
| Overall Study | Progression | 2 | 5 |
Baseline characteristics
| Characteristic | Arm II (Erlotinib) | Total | Arm I (Rilotumumab, Erlotinib) |
|---|---|---|---|
| Age, Continuous | 71.6 years | 72.3 years | 73 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 8 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 7 Participants | 2 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 4 Participants | 7 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Investigator-assessed Progression-free Survival Between Arms
A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to investigator-assessed progression-free survival, comparing the two treatment arms.
Time frame: From date of sub-study registration to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause, assessed up to 18 months since completion of accrual
Population: This study was terminated early and thus no manuscript is forthcoming. Outcomes were not analyzed.
Primary
Objective Response Rate (Confirmed and Unconfirmed, Complete and Partial) Between Arms
Time frame: Up to 3 years
Population: This study was terminated early and thus no manuscript is forthcoming. Outcomes were not analyzed.
Secondary
Frequency and Severity of Toxicities Associated With Investigational Therapy Versus Standard of Care
Time frame: Up to 3 years
Population: This study was terminated early and thus no manuscript is forthcoming. Outcomes were not analyzed.
Other Pre-specified
Treatment Arm Randomization Acceptance Rate
Monitored by the percentage of patients that receive at least one dose of the treatment they are randomized to.
Time frame: Up to 3 years
Population: This study was terminated early and thus no manuscript is forthcoming. Outcomes were not analyzed.