Erlotinib Hydrochloride or Crizotinib and Chemoradiation Therapy in Treating Patients With Stage III Non-small Cell Lung Cancer (NSCLC)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01822496
First received: April 1, 2013
Last updated: September 19, 2014
Last verified: July 2014
  Purpose

This randomized phase II trial studies how well erlotinib hydrochloride or crizotinib and chemoradiation therapy works in treating patients with stage III non-small cell lung cancer. Radiation therapy uses high energy x rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as cisplatin, etoposide, paclitaxel, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving erlotinib hydrochloride is more effective than crizotinib with chemoradiation therapy in treating patients with non-small cell lung cancer.


Condition Intervention Phase
Adenocarcinoma of the Lung
Bronchoalveolar Cell Lung Cancer
Large Cell Lung Cancer
Stage IIIA Non-small Cell Lung Cancer
Stage IIIB Non-small Cell Lung Cancer
Drug: erlotinib hydrochloride
Drug: crizotinib
Radiation: intensity-modulated radiation therapy
Radiation: 3-dimensional conformal radiation therapy
Drug: cisplatin
Drug: etoposide
Drug: paclitaxel
Drug: carboplatin
Other: laboratory biomarker analysis
Phase 2

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 Study of Individualized Combined Modality Therapy for Stage III Non-small Cell Lung Cancer (NSCLC)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: Occurrence of local or regional progression, distant metastases, or death from any cause from the time of randomization to the occurrence of one of the failure events, whichever occurs first, assessed up to 12 months ] [ Designated as safety issue: No ]
    The product limit estimator developed by Kaplan and Meier will be used. Their 95% confidence intervals will be estimated. Comparisons between arms will be conducted using a log rank test.


Secondary Outcome Measures:
  • Proportion of patients who respond (completely or partially) to each treatment, assessed by the Response Evaluation Criteria in Solid Tumors [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Estimated as well as their 95% confidence intervals. Tested using Fisher's exact test and using a logistic regression model to incorporate other prognostic covariates.

  • Incidence of grade 3-5 adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]
    Summarized using frequency table methods.

  • Overall survival [ Time Frame: Time to death from any cause, assessed up to 12 months ] [ Designated as safety issue: No ]
    The product limit estimator developed by Kaplan and Meier will be used. Their 95% confidence intervals will be estimated. Comparisons between arms will be conducted using a log rank test.

  • Local-regional progression free survival [ Time Frame: Time from randomization to local-regional progression or death, whichever comes first, assessed up to 10 years ] [ Designated as safety issue: No ]
    Appropriate methods for competing risks will be applied, specifically cumulative incidence functions for estimation of cumulative cause specific event probabilities with associated testing for differences, and regression methods for cause-specific hazards and subdistribution hazards underlying cumulative incidence functions may be applied accordingly for exploratory purposes.

  • Distant progression free survival [ Time Frame: Time from randomization to distant progression or death, whichever occurs first, assessed up to 10 years ] [ Designated as safety issue: No ]
    Appropriate methods for competing risks will be applied, specifically cumulative incidence functions for estimation of cumulative cause specific event probabilities with associated testing for differences, and regression methods for cause-specific hazards and subdistribution hazards underlying cumulative incidence functions may be applied accordingly for exploratory purposes.

  • Deep sequencing of selected kinomes in patients from whom adequate baseline tissue is available [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 234
Study Start Date: November 2013
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (erlotinib hydrochloride, concurrent chemoradiation)
Patients receive erlotinib hydrochloride PO QD for up to 12 weeks. Patients who have had no response (partial or complete) after 6 weeks undergo concurrent chemoradiation therapy immediately. After 2 weeks of completion of induction therapy, patients receive chemoradiation.
Drug: erlotinib hydrochloride
Given PO
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
Radiation: intensity-modulated radiation therapy
Undergo IMRT
Other Name: IMRT
Radiation: 3-dimensional conformal radiation therapy
Undergo 3-D CRT
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm III (crizotinib, concurrent chemoradiation)
Patients receive crizotinib PO BID for up to 12 weeks. Patients who have had no response (partial or complete) after 6 weeks undergo concurrent chemoradiation therapy immediately. After 2 weeks of completion of induction therapy, patients receive chemoradiation.
Drug: crizotinib
Given PO
Other Names:
  • c-met/hepatocyte growth factor receptor tyrosine kinase inhibitor PF-02341066
  • c-met/HGFR tyrosine kinase inhibitor PF-02341066
  • MET Tyrosine Kinase Inhibitor PF-02341066
  • PF-02341066
Radiation: intensity-modulated radiation therapy
Undergo IMRT
Other Name: IMRT
Radiation: 3-dimensional conformal radiation therapy
Undergo 3-D CRT
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: Arm II (chemoradiation, EGFR TK Mutation Cohort)
Patients receive concurrent chemotherapy with thoracic radiation therapy beginning on day 1. Treatment continues in the absence of disease progression or unacceptable toxicity.
Radiation: intensity-modulated radiation therapy
Undergo IMRT
Other Name: IMRT
Radiation: 3-dimensional conformal radiation therapy
Undergo 3-D CRT
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: Arm IV (chemoradiation, ALK Tran L Cohort)
Patients receive concurrent chemotherapy with thoracic radiation therapy beginning on day 1. Treatment continues in the absence of disease progression or unacceptable toxicity.
Radiation: intensity-modulated radiation therapy
Undergo IMRT
Other Name: IMRT
Radiation: 3-dimensional conformal radiation therapy
Undergo 3-D CRT
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess whether patients with unresectable local-regionally advanced non-small cell lung cancer (NSCLC) treated with targeted agents based on molecular characteristics have a longer progression-free survival than those treated with standard care therapy alone.

SECONDARY OBJECTIVES:

I. To evaluate response rate. II. To assess toxicity. III. To assess overall survival. IV. To correlate clinical outcomes with tumor molecular aberrations identified from deep sequencing of selected kinomes in patients from whom adequate baseline tissue is available.

OUTLINE: Patients are randomized to 1 of 4 treatment arms. Patients are stratified according to mutation status.

ARM I (induction therapy): Patients receive erlotinib hydrochloride orally (PO) once daily (QD) for up to 12 weeks. Patients who have had no response (partial or complete) after 6 weeks undergo concurrent chemoradiation therapy immediately. After 2 weeks of completion of induction therapy, patients receive chemoradiation.

ARM III (induction therapy): Patients receive crizotinib PO twice daily (BID) for up to 12 weeks. Patients who have had no response (partial or complete) after 6 weeks undergo concurrent chemoradiation therapy immediately. After 2 weeks of completion of induction therapy, patients receive chemoradiation.

ARMS II AND IV (concurrent chemoradiation): Patients receive concurrent chemotherapy with thoracic radiation therapy beginning on day 1. Treatment continues in the absence of disease progression or unacceptable toxicity.

CHEMORADIATION: In all treatment arms, patients undergo concurrent intensity modulated radiation therapy (IMRT) or 3-dimensional conformal radiation therapy (3-D CRT) QD 5 days a week for 6 weeks. Patients receive 1 of 2 chemotherapy regimens based on the discretion of the treating physician. Patients receive cisplatin intravenously (IV) over 1-2 hours on days 1, 8, 29, and 36 and etoposide IV over 1 hour on days 1-5 and 29-33. Treatment repeats every 4 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Some patients receive paclitaxel IV and carboplatin IV on days 1, 8, 15, 22, 29, and 36 during radiation therapy for 6 weeks. Two courses of consolidation treatment will begin 4-6 weeks after completion of radiation therapy with paclitaxel IV on days 1 and 22 and carboplatin IV on days 1 and 22 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 1 month, every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years thereafter.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed, newly diagnosed non-squamous NSCLC
  • Unresectable stage IIIA or IIIB disease; patients must be surgically staged to confirm N2 or N3 disease; patients may have invasive mediastinal staging by mediastinoscopy, mediastinotomy, endobronchial ultrasound transbronchial aspiration (EBUS-TBNA), endoscopic ultrasound (EUS), or video-assisted thoracoscopic surgery (VATS)
  • Patients with any tumor (T) with node (N)2 or N3 are eligible; patients with T3, N1-N3 disease are eligible if deemed unresectable; patients with T4, any N are eligible
  • Patients must have measurable disease, i.e., lesions that can be accurately measured in at least 1 dimension (longest dimension in the plane of measurement is to be recorded) with a minimum size of 10 mm by computed tomography (CT) scan (CT scan slice thickness no greater than 5 mm); tumor measurements must be taken within 42 days prior to registration
  • Patients with a pleural effusion, which is a transudate, cytologically negative and non-bloody, are eligible if the radiation oncologist feels the tumor can be encompassed within a reasonable field of radiotherapy
  • If a pleural effusion can be seen on the chest CT but not on chest x-ray and is too small to tap, the patient will be eligible; patients who develop a new pleural effusion after thoracotomy or other invasive thoracic procedure will be eligible
  • The institution's pre-enrollment biomarker screening at a Clinical Laboratory Improvement Amendments (CLIA) certified lab documents presence of known "sensitive" mutations in epidermal growth factor receptor tyrosine kinase (EGFR TK) domain (exon 19 deletion, L858) and/or EML4-anaplastic lymphoma kinase (ALK) fusion arrangement; either the primary tumor or the metastatic lymph node tissue may be used for testing of mutations
  • The institution's pre-enrollment biomarker screening at a CLIA certified lab documents absence of T790M mutation in the EGFR TK domain
  • Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup:

    • History/physical examination, including recording of pulse, blood pressure (BP), weight, and body surface area, within 45 days prior to registration
    • Whole body fludeoxyglucose-positron emission tomography (FDG-PET)/CT (orbits to mid-thighs) within 30 days prior to registration; PET/CT must be negative for distant metastasis
    • CT scan of the chest with contrast (unless medically contraindicated) within 30 days prior to registration
    • Magnetic resonance imaging (MRI) of the brain with contrast (or CT scan with contrast, if MRI medically contraindicated) within 30 days prior to registration
  • Zubrod performance status 0-1 within 14 days prior to registration
  • Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
  • Platelets >= 100,000 cells/mm^3
  • Hemoglobin >= 8.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable)
  • Calculated creatinine clearance >= 50 ml/min (by Cockcroft-Gault formula) within 14 days prior to registration
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN) within 14 days prior to registration
  • Bilirubin within normal institutional limits within 14 days prior to registration
  • Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential
  • Patient must provide study specific informed consent prior to study entry, including consent for mandatory screening of tissue

Exclusion Criteria:

  • Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 730 days (2 years) (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
  • Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
  • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
  • Atelectasis of the entire lung
  • Contralateral hilar node involvement
  • Exudative, bloody, or cytologically malignant effusions
  • Severe, active co-morbidity, defined as follows:

    • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
    • Transmural myocardial infarction within the last 6 months
    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration; hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
    • Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; protocol-specific requirements may also exclude immuno-compromised patients
  • Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
  • Prior allergic reaction to the study drug(s) involved in this protocol
  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: NCT01822496

  Show 63 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Ramaswamy Govindan NRG Oncology Foundation, Inc.
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01822496     History of Changes
Other Study ID Numbers: NCI-2013-00737, NCI-2013-00737, RTOG 1306, RTOG-1306, U10CA021661, U10CA180868
Study First Received: April 1, 2013
Last Updated: September 19, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Adenocarcinoma
Adenocarcinoma, Bronchiolo-Alveolar
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Erlotinib
Crizotinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014