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Trial record 1 of 1 for:    NCT03137771
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Maintenance Chemotherapy With or Without Stereotactic Body Radiation Therapy in Treating Patients With Stage IV Non-small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT03137771
Recruitment Status : Recruiting
First Posted : May 3, 2017
Last Update Posted : November 6, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
NRG Oncology

Brief Summary:
This randomized phase II/III trial studies how well giving maintenance chemotherapy with or without stereotactic body radiation therapy works in treating patients with stage IV non-small cell lung cancer. Drugs used in maintenance chemotherapy, such as docetaxel, pemetrexed disodium, and gemcitabine 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. Stereotactic body radiation therapy is a specialized radiation therapy that sends x-rays directly to the tumor using smaller doses over several days and may cause less damage to normal tissue. Giving maintenance chemotherapy and stereotactic body radiation therapy together may work better than maintenance chemotherapy alone in treating patients with stage IV non-small cell lung cancer.

Condition or disease Intervention/treatment Phase
Recurrent Non-Small Cell Lung Carcinoma Stage IV Non-Small Cell Lung Cancer Radiation: 3-Dimensional Conformal Radiation Therapy (3D-CRT) Drug: Docetaxel Drug: Gemcitabine Radiation: Intensity-Modulated Radiation Therapy (IMRT) Drug: Pemetrexed Disodium Radiation: Stereotactic Body Radiation Therapy (SBRT) Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

Phase II

To evaluate the impact of adding stereotactic body radiation therapy (SBRT) to maintenance systemic therapy versus maintenance systemic therapy alone on progression-free survival for patients with metastatic non-small cell lung cancer (NSCLC) with no evidence of progression and limited metastatic sites after first-line systemic therapy.

Phase III

To evaluate the impact of adding SBRT to maintenance systemic therapy versus maintenance systemic therapy alone on overall survival for patients with metastatic NSCLC with no evidence of progression and limited metastatic sites after first-line systemic therapy.

SECONDARY OBJECTIVES:

I. To evaluate the impact of adding SBRT to maintenance systemic therapy versus maintenance systemic therapy alone on in-field local failure.

II. To evaluate the impact of adding SBRT to maintenance systemic therapy versus maintenance systemic therapy alone on primary failure.

III. To evaluate the impact of adding SBRT to maintenance systemic therapy versus maintenance systemic therapy alone on out-of-field disease progression.

IV. To evaluate the impact of adding SBRT to maintenance systemic therapy versus maintenance systemic therapy alone on toxicity.

V. To evaluate the impact of adding SBRT to maintenance systemic therapy versus maintenance systemic therapy alone on duration of maintenance systemic chemotherapy usage.

VI. To evaluate the effect of adding SBRT to systemic therapy in limited stage IV NSCLC on Quality of Life (QOL)

OUTLINE: Patients are randomized into 1 of 2 arms.

ARM 1 (CHEMOTHERAPY ALONE): Patients may receive docetaxel intravenously (IV) over 60 minutes on Day 1, or gemcitabine IV over 30 minutes on Days 1 and 8. Patients with non-squamous non-small cell lung cancer may receive pemetrexed disodium IV over 10 minutes on Day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM 2 (SBRT AND CHEMOTHERAPY): Patients undergo SBRT to all sites of metastases (≤3 discrete sites) plus irradiation of the primary site (SBRT or hypofractionated RT) followed by chemotherapy as in Arm 1.

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


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Maintenance Systemic Therapy Versus Consolidative Stereotactic Body Radiation Therapy (SBRT) Plus Maintenance Systemic Therapy for Limited Metastatic Non-Small Cell Lung Cancer (NSCLC): A Randomized Phase II/III Trial
Actual Study Start Date : April 7, 2017
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : April 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Active Comparator: Arm 1 (maintenance chemotherapy)
Patients may receive docetaxel IV over 60 minutes on Day 1, or gemcitabine IV over 30 minutes on Days 1 and 8. Patients with non-squamous non-small cell lung cancer may receive pemetrexed disodium IV over 10 minutes on Day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: Docetaxel
Given IV
Other Names:
  • Docecad
  • RP56976
  • Taxotere
  • Taxotere Injection Concentrate

Drug: Gemcitabine
Given IV
Other Names:
  • dFdC
  • dFdCyd
  • Difluorodeoxycytidine

Drug: Pemetrexed Disodium
Given IV
Other Names:
  • Alimta
  • LY231514
  • N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic Acid Disodium Salt

Experimental: Arm 2 (SBRT + maintenance chemotherapy)
Patients undergo SBRT over 2-4 weeks. If SBRT cannot be used to treat primary disease sites, patients also undergo IMRT or 3D-CRT over 3-5 weeks. Within 2 weeks after completion of radiation therapy, patients receive chemotherapy as in Arm 1 (docetaxel IV over 60 minutes on Day 1, or gemcitabine IV over 30 minutes on Days 1 and 8. Patients with non-squamous non-small cell lung cancer may receive pemetrexed disodium IV over 10 minutes on Day 1).
Radiation: 3-Dimensional Conformal Radiation Therapy (3D-CRT)
Undergo 3DCRT
Other Names:
  • 3-dimensional conformal radiation therapy
  • 3-dimensional radiation therapy
  • 3D CONFORMAL RADIATION THERAPY
  • 3D CRT
  • 3D-CRT
  • Conformal Therapy
  • Radiation Conformal Therapy

Drug: Docetaxel
Given IV
Other Names:
  • Docecad
  • RP56976
  • Taxotere
  • Taxotere Injection Concentrate

Drug: Gemcitabine
Given IV
Other Names:
  • dFdC
  • dFdCyd
  • Difluorodeoxycytidine

Radiation: Intensity-Modulated Radiation Therapy (IMRT)
Undergo IMRT
Other Names:
  • IMRT
  • Intensity Modulated RT
  • INTENSITY-MODULATED RADIATION THERAPY
  • Intensity-Modulated Radiotherapy

Drug: Pemetrexed Disodium
Given IV
Other Names:
  • Alimta
  • LY231514
  • N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic Acid Disodium Salt

Radiation: Stereotactic Body Radiation Therapy (SBRT)
Undergo SBRT
Other Names:
  • SBRT
  • stereotactic body radiation therapy




Primary Outcome Measures :
  1. Phase II - Progression-Free Survival (PFS) [ Time Frame: From the time of randomization to date any documented progression or death due to any cause, whichever occurs first. Assessed for up to 3 years. ]
    Progression-Free Survival

  2. Phase III - Overall Survival (OS) [ Time Frame: From the time of randomization to date of death due to any cause. Assessed up to 3 years. ]
    Overall Survival


Secondary Outcome Measures :
  1. Time to In-Field Failure [ Time Frame: Time from randomization to progression within the irradiated field at any time, assessed for up to 3 years ]
    The time it takes for disease progression to occur within the radiation treatment field of disease will be measured.

  2. Time to Out-of-Field Failure [ Time Frame: Time from randomization to out-field disease progression, assessed for up to 3 years ]
    The time is takes for disease progression to occur outside of the radiation treatment field of disease will be measured.

  3. Incidence of adverse events graded per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4 [ Time Frame: Up to 3 years ]
    Will be reported with the frequency and severity (e.g., type, grade, and attribution) by arm.

  4. Duration of Maintenance Chemotherapy Usage [ Time Frame: Up to 3 years ]
    Will be performed on an intent to treat basis.



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 have the psychological ability and general health that permits completion of the study requirements and required follow up
  • Women of childbearing potential and men who are sexually active should be willing and able to use medically acceptable forms of contraception during the trial
  • Pathologically proven diagnosis of NSCLC, with metastases (stage IV disease) present prior to registration; this includes patients newly diagnosed with metastatic disease or those initially diagnosed and treated for stage I-III NSCLC who ultimately develop metastases
  • Appropriate stage for study entry based on the following diagnostic workup:

    • History/physical examination within 30 days prior to registration
    • Imaging proof of limited metastatic disease and response to therapy/stable disease, by at least CT chest through the adrenals or PET/CT within 30 days prior to registration
  • Zubrod performance status 0, 1, or 2 within 30 days prior to registration
  • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × upper limit of normal (ULN) or ≤ 5 × ULN with metastatic liver disease
  • Total bilirubin ≤ 1.5 × ULN
  • Absolute neutrophil count (ANC) ≥ 500 cells/mm^3
  • Creatinine clearance ≥ 45 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Platelets ≥ 50,000 cells/mm^3
  • Negative serum pregnancy test within one week prior to registration for females of childbearing potential
  • Patients must have received first-line/induction chemotherapy (4 cycles) and achieved stable disease or a partial response
  • Prior systemic chemotherapy as part of concurrent treatment approach for previously diagnosed stage III NSCLC, as adjuvant therapy for previously resected NSCLC, or for other previous cancers is permitted
  • Prior radiotherapy for patients with brain metastases prior to enrollment is acceptable
  • Patients must have measurable disease at baseline and 3 or fewer discrete, extracranial metastatic disease sites that are technically amenable to SBRT
  • For de novo stage IV NSCLC patients (patients with metastatic disease at first presentation), primary disease must be treatable with local therapy in the form of SBRT or hypofractionated radiation; if the primary disease is found in the peripheral or central lung parenchyma without nodal disease for instance, SBRT may be employed; if primary disease is more advanced with involvement of the mediastinum (T4 tumor, N1-N3 disease, etc.), these volumes should be technically treatable with hypofractionated radiation
  • If primary disease in the thoracic cavity was previously treated with local therapy in the form of surgery, any local/regional disease recurrence should be technically treatable with SBRT or hypofractionated radiation after induction systemic therapy
  • Patients must be registered within 35 days of administration of the last dose of first-line/induction systemic therapy
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
  • Patients with brain metastases are eligible if these lesions have been previously treated and the patients have no clinical or radiographic evidence of progression prior to enrollment

Exclusion Criteria:

  • Clinical or radiologic evidence of untreated and/or progressive brain metastases
  • Cutaneous metastasis of NSCLC
  • Metastatic disease invading the esophagus, stomach, intestines, or mesenteric lymph nodes
  • Prior invasive malignancy (except non-melanomatous skin cancer, low or intermediate risk prostate cancer, or in situ carcinoma of breast, oral cavity, skin, or cervix) unless disease free for a minimum of one year
  • Metastases located within 3 cm of previously irradiated (< 3Gy per fraction) structures if:

    • Spinal cord previously irradiated to > 40 Gy
    • Brachial plexus previously irradiated to > 50 Gy
    • Small intestine, large intestine, or stomach previously irradiated to > 45 Gy
    • Brainstem previously irradiated to > 50 Gy
    • Lung previously irradiated with prior V20 Gy > 35%
  • Patients receiving targeted therapy (non-cytotoxic systemic therapy) for NSCLC in the first-line setting
  • If a patient has progressed in previous areas of primary disease that received definitive doses of radiation, these patients would require re-irradiation in previous high dose anatomic areas and are not eligible for this study
  • Patients with malignant pleural effusions that do not resolve after first-line systemic therapy; patients with pleural effusions that have become too small for thoracentesis at the time of registration would be permitted on study, indicating a significant response to first-line chemotherapy
  • Patients with more than 3 discrete locations of extra-cranial metastatic disease after first-line systemic therapy requiring more than 3 SBRT plans to cover these distinct metastatic disease entities
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
  • Patients who are pregnant or nursing
  • Participation in any investigational drug study (excluding non-oncology and/or symptom management studies) within 4 weeks prior to registration
  • Known human immunodeficiency virus (HIV) positive with cluster of differentiation 4 (CD4) count < 200 cells/microliter; note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count ≥ 200 cells/microliter within 30 days prior to registration; note also that HIV testing is not required for eligibility for this protocol

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): NCT03137771


  Show 159 Study Locations
Sponsors and Collaborators
NRG Oncology
National Cancer Institute (NCI)
Investigators
Principal Investigator: Puneeth Iyengar NRG Oncology

Responsible Party: NRG Oncology
ClinicalTrials.gov Identifier: NCT03137771     History of Changes
Other Study ID Numbers: NRG-LU002
NCI-2016-00849 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NRG-LU002 ( Other Identifier: NRG Oncology )
NRG-LU002 ( Other Identifier: CTEP )
U10CA180868 ( U.S. NIH Grant/Contract )
First Posted: May 3, 2017    Key Record Dates
Last Update Posted: November 6, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Gemcitabine
Pemetrexed
Docetaxel
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors