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Lung-MAP: Rilotumumab and Erlotinib Hydrochloride or Erlotinib Hydrochloride Alone as Second-Line Therapy in Treating Patients With Recurrent Stage IV Squamous Cell Lung Cancer and Positive Biomarker Matches

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ClinicalTrials.gov Identifier: NCT02926638
Recruitment Status : Active, not recruiting
First Posted : October 6, 2016
Last Update Posted : December 20, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Southwest Oncology Group

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.

Condition or disease Intervention/treatment Phase
MET Positive Recurrent Squamous Cell Lung Carcinoma Stage IV Squamous Cell Lung Carcinoma AJCC v7 Drug: Erlotinib Hydrochloride Other: Laboratory Biomarker Analysis Biological: Rilotumumab Phase 2 Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 310 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : June 16, 2014
Estimated Primary Completion Date : April 1, 2022
Estimated Study Completion Date : April 1, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: 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)
Drug: Erlotinib Hydrochloride
Given PO
Other Names:
  • Cp-358,774
  • OSI-774
  • Tarceva

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Rilotumumab
Given IV
Other Names:
  • AMG 102
  • Anti-HGF Monoclonal Antibody AMG 102
  • Fully Human Anti-HGF Monoclonal Antibody AMG 102

Active Comparator: 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)
Drug: Erlotinib Hydrochloride
Given PO
Other Names:
  • Cp-358,774
  • OSI-774
  • Tarceva

Other: Laboratory Biomarker Analysis
Correlative studies




Primary Outcome Measures :
  1. Investigator-assessed progression-free survival as defined by Response Evaluation Criteria in Solid Tumors 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 ]
    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.

  2. Investigator-assessed progression-free survival in patients with advanced stage refractory squamous cell carcinoma of the lung randomized to receive investigational therapy versus standard of care (Design #2, Phase III) [ Time Frame: Up to 3 years ]
    Estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals for median investigator-assessed progression-free survival. A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to progression-free survival comparing the two treatment arms at the levels specified.

  3. Less than 33% improvement in median investigator-assessed progression-free survival as defined as Response Evaluation Criteria in Solid Tumors 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 ]
    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. A Cox proportional hazards model will be used to estimate the hazard ratios and associated confidence intervals.

  4. Objective response rate (confirmed and unconfirmed, complete and partial) (Design #2, Phase II) [ Time Frame: Up to 3 years ]
    The investigational therapy arm will be judged to have provided sufficient evidence to proceed to the phase III component if the overall response rate is at least 25%. Response rates and associated confidence intervals will be calculated.

  5. Overall survival (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 ]
    A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to overall survival, comparing the two treatment arms. A Cox proportional hazards model will be used to estimate the hazard ratios and associated confidence intervals.

  6. Overall survival in patients with advanced stage refractory squamous cell carcinoma of the lung randomized to receive investigational therapy versus standard of care (Design #2, Phase III) [ Time Frame: Up to 3 years ]
    The Brookmeyer-Crowley method will be used to calculate confidence intervals for median overall survival. A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to overall survival comparing the two treatment arms at the levels specified.


Secondary Outcome Measures :
  1. Duration of response among patients who achieve a complete response or partial response by Response Evaluation Criteria in Solid Tumors 1.1 (Design #2, Phase II) [ Time Frame: Up to 3 years ]
    Estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals for median duration of response.

  2. Frequency and severity of toxicities associated with investigational therapy versus standard of care (Design #2, Phase III) [ Time Frame: Up to 3 years ]
    Analysis of toxicities will be performed using a chi-square or Fisher?s exact test, as appropriate.

  3. Investigator-assessed progression-free survival, censoring patients with symptomatic deterioration at the time of symptomatic deterioration (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 ]
    Investigator-assessed progression-free survival will be measured.

  4. Overall survival with investigational therapy (Design #2, Phase II) [ Time Frame: Up to 3 years ]
    A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to overall survival comparing the two treatment arms at the levels specified. A Cox proportional hazards model will be used to estimate the hazard ratios and associated confidence intervals.

  5. Progression-free survival with investigational therapy (Design #2, Phase II) [ Time Frame: Up to 3 years ]
    A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to progression-free survival comparing the two treatment arms at the levels specified. A Cox proportional hazards model will be used to estimate the hazard ratios and associated confidence intervals.

  6. Response rate (confirmed and unconfirmed) in patients with measurable disease as defined by Response Evaluation Criteria in Solid Tumors 1.1 (Design #1, Phase II and III) [ Time Frame: Up to 3 years ]
    Analysis will be performed using a chi squared or Fisher's exact test, as appropriate. Response proportions will be compared using a 1-sided Fisher?s exact test at the 0.001 level.

  7. Response rates (confirmed and unconfirmed, complete and partial) among patients randomized to receive investigational therapy versus standard of care (Design #2, Phase III) [ Time Frame: Up to 3 years ]
    Analysis of response rates will be performed using a chi-square or Fisher's exact test, as appropriate.

  8. Severity of toxicities associated with investigational therapy versus standard of care (Design #2, Phase II) [ Time Frame: Up to 3 years ]
    Analysis of toxicities will be performed using a chi-square or Fisher's exact test, as appropriate.

  9. Toxicity frequencies, monitored using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Design #1, Phase II and III) [ Time Frame: Up to 3 years ]
    Analysis will be performed using a chi squared or Fisher's exact test, as appropriate.


Other Outcome Measures:
  1. Screen success rate [ Time Frame: Up to 3 years ]
    Monitored by the percentage of screened patients that register to a therapeutic sub-study.

  2. Treatment arm randomization acceptance rate [ Time Frame: Up to 3 years ]
    Monitored by the percentage of patients that receive at least one dose of the treatment they are randomized to.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02926638


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Sponsors and Collaborators
Southwest Oncology Group
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Vassiliki Papadimitrakopoulou Southwest Oncology Group

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Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT02926638     History of Changes
Other Study ID Numbers: S1400E
NCI-2014-01382 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
S1400E
S1400E ( Other Identifier: SWOG )
S1400E ( Other Identifier: CTEP )
U10CA180888 ( U.S. NIH Grant/Contract )
First Posted: October 6, 2016    Key Record Dates
Last Update Posted: December 20, 2018
Last Verified: December 2018

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Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Carcinoma
Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Rilotumumab
Erlotinib Hydrochloride
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action