Trial record 2 of 7 for:    afatinib cetuximab

S1403, Afatinib Dimaleate With or Without Cetuximab in Treating Patients With Newly Diagnosed Stage IV or Recurrent, EGFR Mutation Positive Non-small Cell Lung Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2015 by Southwest Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT02438722
First received: May 6, 2015
Last updated: NA
Last verified: May 2015
History: No changes posted
  Purpose

This randomized phase II/III trial studies how well afatinib dimaleate with cetuximab works and compares it with afatinib dimaleate alone in treating patients with newly diagnosed stage IV or recurrent (has come back), epidermal growth factor receptor (EGFR) mutation positive non-small cell lung cancer. Afatinib dimaleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab, may block tumor growth in different ways by targeting certain cells. It is not yet known whether afatinib dimaleate is more effective when given alone or with cetuximab in treating patients with non-small cell lung cancer.


Condition Intervention Phase
Recurrent Non-Small Cell Lung Carcinoma
Stage IV Non-Small Cell Lung Cancer
Drug: Afatinib Dimaleate
Biological: Cetuximab
Other: Laboratory Biomarker Analysis
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II/III Trial of Afatinib Plus Cetuximab Versus Afatinib Alone in Treatment-Naive Patients With Advanced, EGFR Mutation Positive Non-small Cell Lung Cancer (NSCLC)

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • OS (phase III) [ Time Frame: From date of registration to date of death due to any cause, assessed up to 3 years ] [ Designated as safety issue: No ]
  • PFS (phase II) [ Time Frame: From date of registration to date of first documentation of progression or symptomatic deterioration or death due to any cause, assessed up to 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • PFS [ Time Frame: From date of registration to date of first documentation of progression or symptomatic deterioration or death due to any cause, assessed up to 3 years ] [ Designated as safety issue: No ]
  • Response rates [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Compared between arms using a chi-squared test of independence at the 1-sided 5% level.

  • Time to treatment discontinuation [ Time Frame: From date of registration to date of discontinuation of treatment or death due to any cause, assessed up to 3 years ] [ Designated as safety issue: No ]
  • Time to treatment failure [ Time Frame: From date of registration to date of first documentation of progression or symptomatic deterioration, early discontinuation of treatment, or death due to any cause, assessed up to 3 years ] [ Designated as safety issue: No ]
  • Toxicity rates assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
    Assessed using a chi-squared or Fisher's exact test (as appropriate) at the 1-sided 5% level.


Other Outcome Measures:
  • Change in copy number alterations in MET, EGFR, and HER2, analyzed using fluorescence in situ hybridization [ Time Frame: Baseline up to 3 years (after disease progression) ] [ Designated as safety issue: No ]
    For each of these markers, a one-sample t-test (or Wilcoxon signed-rank test) will be used to test the null hypothesis that the absolute difference between the copy number after progression and the copy number in the pre-treatment specimen (or an appropriate transformation of the difference, determined after exploratory data analysis) is not equal to zero.

  • Change in the ratio of sensitizing EGFR mutation to EGFR T790 mutation [ Time Frame: Baseline up to 3 years (at progression) ] [ Designated as safety issue: No ]
    To evaluate if EGFRs/EGFR T790M is lower at progression than in pre-treatment specimens among patients with results available for pre-treatment and progression, a one-sample t-test (or Wilcoxon signed-rank test) will be used to test the null hypothesis that the difference between the progression ratio and the pre-treatment ratio (or an appropriate transformation of the difference, determined after exploratory data analysis) is greater than zero in favor of the alternative that the difference is less than zero.

  • EGFR immunohistochemistry H-score [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    To evaluate the hypothesis that H-score positive status at baseline is associated with absolute difference in PFS (and OS) among patients randomized to receive afatinib dimaleate monotherapy a test of interaction will be performed at the 1-sided 20% level.

  • Levels of circulating tumor markers [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Tumor marker levels over time will be evaluated using a linear mixed model for continuous markers and using generalized estimating equations for binary markers. A landmark analysis will be used to evaluate the correlation between post-randomization biomarker values and PFS and OS (from the landmark timepoint) using a Cox proportional hazards model.

  • Presence of de novo EGFR T790M mutation or other molecular alterations [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    To evaluate if the presence of de novo T790M mutation is associated with primary resistance to afatinib dimaleate, PFS and OS will be compared between T790M mutation positive and negative patients randomized to the afatinib dimaleate monotherapy arm.

  • Ratio of sensitizing EGFR mutation to EGFR T790 mutation [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    To evaluate if the ratio of EGFR sensitizing mutation to EGFR T790M mutation (EGFRs/EGFR T790M) among patients with T790M is predictive for afatinib dimaleate monotherapy, analyses will be performed in a similar fashion to the evaluation of T790M among patients with measurable T790M (which defines T790M). Cox regression will be used to assess the predictive association of the ratio in the afatinib dimaleate.


Estimated Enrollment: 605
Study Start Date: March 2015
Estimated Primary Completion Date: February 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (afatinib dimaleate, cetuximab)
Patients receive afatinib dimaleate PO QD on days 1-28 and cetuximab IV over 2 hours on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Afatinib Dimaleate
Given PO
Other Names:
  • (2E)-N-(4-((3-Chloro-4-fluorophenyl)amino)-7-(((3S)-tetrahydrofuran-3-yl)oxy)quinazolin- 6-yl)-4-(dimethylamino)but-2-enamide bis(hydrogen (2Z)-but-2-enedioate)
  • AFATINIB DIMALEATE
  • BIBW 2992MA2
  • BIBW2992 MA2
  • Gilotrif
Biological: Cetuximab
Given IV
Other Names:
  • CETUXIMAB
  • Chimeric Anti-EGFR Monoclonal Antibody
  • Chimeric MoAb C225
  • Chimeric Monoclonal Antibody C225
  • Erbitux
  • IMC-C225
Other: Laboratory Biomarker Analysis
Correlative studies
Active Comparator: Arm II (afatinib dimaleate)
Patients receive afatinib dimaleate as in Arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Afatinib Dimaleate
Given PO
Other Names:
  • (2E)-N-(4-((3-Chloro-4-fluorophenyl)amino)-7-(((3S)-tetrahydrofuran-3-yl)oxy)quinazolin- 6-yl)-4-(dimethylamino)but-2-enamide bis(hydrogen (2Z)-but-2-enedioate)
  • AFATINIB DIMALEATE
  • BIBW 2992MA2
  • BIBW2992 MA2
  • Gilotrif
Other: Laboratory Biomarker Analysis
Correlative studies

  Show Detailed Description

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed stage IV (American Joint Committee on Cancer [AJCC] 7th Edition) or recurrent non-small cell lung cancer (NSCLC)
  • Patients must have documented presence of a sensitizing EGFR mutation; patients with mutations known to be resistant to EGFR exon 19 deletion or exon 21 (L858R) substitution mutation; T790M mutation or other molecular abnormality will be allowed as long as it accompanies one of the mutations listed above; EGFR testing must be performed using Food and Drug Administration (FDA)-approved test or in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.
  • Patients must have tissue available and must agree to submission of tissue and blood; one to two paraffin-embedded tissue blocks or 15-20 unstained slides are requested (a minimum of 12 slides is required); cytology (i.e. fine-needle aspirations, pleural effusion specimens) is acceptable if a cell block or sufficient unstained slides are available; tumor material must be reviewed by a local pathologist who must confirm that at least 100 viable tumor cells are present in the sample and sign the S1403 Pathology Review Form; patients must also be willing to submit blood samples for correlative research at baseline, during treatment and at progression
  • Patients enrolled at sites participating in the Repeat Biopsy Study must agree to submission of tissue obtained by a repeat biopsy performed at the time of disease progression
  • Patients must not have received any prior systemic anticancer therapy for advanced or metastatic disease including chemotherapy or EGFR tyrosine kinase inhibitor therapy (including gefitinib, erlotinib, afatinib, or any experimental EGFR tyrosine kinase inhibitors [TKI] agents); prior chemotherapy for non-metastatic disease (i.e. adjuvant therapy or concurrent chemo-radiotherapy) is allowed as long as > 12 months has passed since completion of therapy; adjuvant EGFR-directed therapy is not allowed; local therapy (i.e. palliative radiotherapy) is allowed as long as a period of 7 days has passed since the last dose was received and the patient has recovered from any associated toxicity at the time of registration
  • Patients may have measurable or non-measurable disease documented by computed tomography (CT) or magnetic resonance imaging (MRI) within 42 days prior to registration; the CT from a combined positron emission tomography (PET)/CT may be used only if it is of diagnostic quality; laboratory parameters are not acceptable as the only evidence of disease; in order to qualify as measurable, measurable disease must be outside previous radiation field; all disease must be assessed and documented on the Baseline Tumor Assessment Form (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1)
  • Patients must have a CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to registration; patient must not have symptomatic brain metastases or evidence of leptomeningeal carcinomatosis; patients with asymptomatic brain metastases are eligible if off of steroids for at least 7 days prior to registration without development of symptoms
  • Patients must not have any known clinically active interstitial lung disease
  • Absolute neutrophil count (ANC) >= 1,500/mcL
  • Platelets >= 75,000/mcL
  • Hemoglobin >= 9 g/dL
  • Total bilirubin =< 1.5 x institutional upper limit of normal (IULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x IULN (or =< 5 x IULN for patients with known liver metastases)
  • Serum creatinine =< 1.5 x IULN OR measured or calculated creatinine clearance >= 60 mL/min
  • Patients must not have significant gastrointestinal disorders with diarrhea as a major symptom (e.g. Crohn's disease, malabsorption, etc)
  • Patients must be able to swallow medication by oral route
  • Patients must not have a history of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) classification of 3, unstable angina or poorly controlled arrhythmia or myocardial infarction within 6 months prior to registration; if clinically indicated, echocardiogram or multigated acquisition (MUGA) must be performed and cardiac ejection fraction must be >= 50%
  • Patients must not have had major surgery within 28 days prior to registration or be scheduled for surgery during the projected course of protocol treatment; tumor biopsy is allowed
  • Patients must not have a known history of active hepatitis B infection (defined as presence of hepatitis B surface antigen [Hep B sAg] and/ or Hep B deoxyribonucleic acid [DNA]), active hepatitis C infection (defined as presence of hepatitis C [Hep C] ribonucleic acid [RNA]) and/or known human immunodeficiency virus (HIV) seropositive
  • Patients must not have any other concomitant serious illness or organ system dysfunction which in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety of the study drug
  • Patients must not be planning to receive any other investigational agents during the course of protocol treatment
  • Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to afatinib and/or cetuximab
  • Prestudy history and physical must be obtained with 28 days prior to registration
  • Patients must have Zubrod performance status of 0 - 2
  • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years
  • Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
  • Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
  • As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02438722

  Show 47 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Investigators
Principal Investigator: Sarah Goldberg Southwest Oncology Group
  More Information

No publications provided

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT02438722     History of Changes
Other Study ID Numbers: S1403, NCI-2014-02405, S1403, S1403, U10CA180888
Study First Received: May 6, 2015
Last Updated: May 6, 2015
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Cetuximab
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Antibodies
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on May 27, 2015