Overview

This trial is active, not recruiting.

Conditions recurrent squamous cell lung carcinoma, stage iv squamous cell lung carcinoma
Treatments erlotinib hydrochloride, laboratory biomarker analysis, rilotumumab
Phase phase 2/phase 3
Targets c-MET, EGFR
Sponsor Southwest Oncology Group
Collaborator National Cancer Institute (NCI)
Start date June 2014
End date April 2022
Trial size 310 participants
Trial identifier NCT02926638, NCI-2014-01382, S1400E, U10CA180888

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Patients receive rilotumumab IV on day 1 and erlotinib hydrochloride PO daily. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
erlotinib hydrochloride Cp-358,774
Given PO
laboratory biomarker analysis
Correlative studies
rilotumumab AMG 102
Given IV
(Active Comparator)
Patients receive erlotinib hydrochloride PO daily. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
erlotinib hydrochloride Cp-358,774
Given PO
laboratory biomarker analysis
Correlative studies

Primary Outcomes

Measure
IA-PFS as defined by RECIST 1.1 (Design #1, Phase II)
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
IA-PFS in patients with advanced stage refractory squamous cell carcinoma (SCCA) of the lung randomized to receive investigational therapy versus standard of care (SoC) (Design #2, Phase III)
time frame: Up to 3 years
Less than 33% improvement in median IA-PFS as defined as RECIST 1.1 (Design #1, Phase III)
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
Objective Response Rate (ORR) (confirmed and unconfirmed, complete and partial) (Design #2, Phase II)
time frame: Up to 3 years
OS (Design #1, Phase III)
time frame: From date of sub-study registration (or date of screening registration if patient never enrolls in a sub-study) to date of death due to any cause, assessed up to 3 years
OS in patients with advanced stage refractory SCCA of the lung randomized to receive investigational therapy versus SoC (Design #2, Phase III)
time frame: Up to 3 years

Secondary Outcomes

Measure
DoR among patients who achieve a CR or PR by RECIST 1.1 (Design #2, Phase II)
time frame: Up to 3 years
Frequency and severity of toxicities associated with investigational therapy versus SoC (Design #2, Phase III)
time frame: Up to 3 years
IA-PFS, censoring patients with symptomatic deterioration (SD) at the time of SD (Design #1, Phase III)
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 3 years
OS with investigational therapy (Design #2, Phase II)
time frame: Up to 3 years
PFS with investigational therapy (Design #2, Phase II)
time frame: Up to 3 years
Response rate (confirmed and unconfirmed) in patients with measurable disease as defined by RECIST 1.1 (Design #1, Phase II and III)
time frame: Up to 3 years
Response rates (confirmed and unconfirmed, complete and partial) among patients randomized to receive investigational therapy versus SoC (Design #2, Phase III)
time frame: Up to 3 years
Severity of toxicities associated with investigational therapy versus SoC (Design #2, Phase II)
time frame: Up to 3 years
Toxicity frequencies, monitored using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Design #1, Phase II and III)
time frame: Up to 3 years

Eligibility Criteria

Male or female participants at least 18 years old.

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 - Biomarker Eligibility Rilotumumab HGF S1400E : patients must be C-MET positive as determined from the tissue submitted to Foundation Medicine for biomarker profiling and MET-IHC using the Dako MET-IHC pharm DX kit - If randomized to arm I, 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 treatment arm randomization - Patients must not have received prior treatment with inhibitors of the 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 cytochrome p450, family 3, subfamily A, polypeptide 4 (CYP3A4) substrates

Additional Information

Official title A Phase II/III Randomized Study of Rilotumumab Plus Erlotinib Versus Erlotinib as Second Line Therapy for C-Met Positive Patients With Stage IV Squamous Cell Lung Cancer (Lung- Map Sub-Study)
Principal investigator Vassiliki Papadimitrakopoulou
Description PRIMARY OBJECTIVES: I. To evaluate if there is sufficient evidence to continue to the phase III component of the sub-study 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 with measurable disease 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 with measureable disease 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 each sub-study defined as the percentage of patients randomized to a treatment arm that receive any protocol treatment. II. To identify additional predictive 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: Patients receive rilotumumab intravenously (IV) 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: 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.
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Southwest Oncology Group.