Clinical Trials /

Maintenance Chemotherapy With or Without Local Consolidative Therapy in Treating Patients With Stage IV Non-small Cell Lung Cancer

NCT03137771

Description:

This randomized phase II/III trial studies how well giving maintenance chemotherapy with or without local consolidation therapy works in treating patients with stage IV non-small cell lung cancer. Drugs used in maintenance chemotherapy, such as docetaxel, pemetrexed disodium, erlotinib hydrochloride, 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. Local consolidation therapy such as radiation/stereotactic body radiation or surgery may kill cancer cells left after initial treatment. Giving maintenance chemotherapy and local consolidation therapy together may work better than maintenance chemotherapy alone in treating patients with stage IV non-small cell lung cancer.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
  • Squamous Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Maintenance Chemotherapy With or Without Local Consolidative Therapy in Treating Patients With Stage IV Non-small Cell Lung Cancer
  • Official Title: Maintenance Systemic Therapy Versus Local Consolidative Therapy (LCT) Plus Maintenance Systemic Therapy for Limited Metastatic Non-Small Cell Lung Cancer (NSCLC): A Randomized Phase II/III Trial

Clinical Trial IDs

  • ORG STUDY ID: NRG-LU002
  • SECONDARY ID: NCI-2016-00849
  • SECONDARY ID: NRG-LU002
  • SECONDARY ID: NRG-LU002
  • SECONDARY ID: U10CA180868
  • NCT ID: NCT03137771

Conditions

  • Recurrent Non-Small Cell Lung Carcinoma
  • Stage IV Non-Small Cell Lung Cancer

Interventions

DrugSynonymsArms
DocetaxelDocecad, RP56976, Taxotere, Taxotere Injection ConcentrateArm 1 (maintenance chemotherapy)
GemcitabinedFdC, dFdCyd, DifluorodeoxycytidineArm 1 (maintenance chemotherapy)
Pemetrexed DisodiumAlimta, 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 SaltArm 1 (maintenance chemotherapy)
Erlotinib HydrochlorideTarcevaArm 1 (maintenance chemotherapy)
PembrolizumabKeytrudaArm 1 (maintenance chemotherapy)

Purpose

This randomized phase II/III trial studies how well giving maintenance chemotherapy with or without local consolidation therapy works in treating patients with stage IV non-small cell lung cancer. Drugs used in maintenance chemotherapy, such as docetaxel, pemetrexed disodium, erlotinib hydrochloride, 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. Local consolidation therapy such as radiation/stereotactic body radiation or surgery may kill cancer cells left after initial treatment. Giving maintenance chemotherapy and local consolidation therapy together may work better than maintenance chemotherapy alone in treating patients with stage IV non-small cell lung cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      Phase II

      To evaluate the impact of adding local consolidative therapy (LCT) 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 LCT 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 LCT to maintenance systemic therapy versus maintenance
      systemic therapy alone on in-field local failure.

      II. To evaluate the impact of adding LCT to maintenance systemic therapy versus maintenance
      systemic therapy alone on the time to development of new lesions.

      III. To evaluate the impact of adding LCT to maintenance systemic therapy versus maintenance
      systemic therapy alone on toxicity.

      IV. To evaluate the impact of adding LCT to maintenance systemic therapy versus maintenance
      systemic therapy alone on duration of maintenance systemic therapy usage.

      V. To evaluate the effect of adding LCT to systemic therapy in limited stage IV NSCLC on
      Quality of Life (QOL) VI. To collect biospecimens and evaluate the correlation between
      clinical outcomes and circulating tumor DNA (ctDNA).

      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, erlotinib hydrochloride orally (PO) once daily (QD), 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 alone or in combination with pembrolizumab IV
      over 30 minutes. Courses repeat every 21 days in the absence of disease progression or
      unacceptable toxicity.

      ARM 2 (SBRT AND CHEMOTHERAPY): Patients undergo LCT over 2-4 weeks. If LCT cannot be used to
      treat primary disease sites, patients also undergo intensity-modulated radiation therapy
      (IMRT) or 3-dimensional conformal radiation therapy (3DCRT) over 3-5 weeks. Within 2 weeks
      after completion of radiation therapy, patients receive chemotherapy as in Arm 1. Patients
      may possibly undergo surgery.

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

Trial Arms

NameTypeDescriptionInterventions
Arm 1 (maintenance chemotherapy)Active ComparatorPatients may receive docetaxel IV over 60 minutes on day 1, erlotinib hydrochloride PO QD, 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 alone or in combination with pembrolizumab IV over 30 minutes. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
  • Docetaxel
  • Gemcitabine
  • Pemetrexed Disodium
  • Erlotinib Hydrochloride
  • Pembrolizumab
Arm 2 (SBRT + maintenance chemotherapy)ExperimentalPatients undergo LCT over 2-4 weeks. If LCT cannot be used to treat primary disease sites, patients also undergo IMRT or 3DCRT over 3-5 weeks. Within 2 weeks after completion of radiation therapy, patients receive chemotherapy as in Arm 1. Patients may possibly undergo surgery.
  • Docetaxel
  • Gemcitabine
  • Pemetrexed Disodium
  • Erlotinib Hydrochloride
  • Pembrolizumab

Eligibility 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 and for up to
             180 days after completion of all treatment to prevent pregnancy or fathering a child.

          -  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 if not a candidate for surgery for these lesions

          -  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 if not a candidate for surgery for these lesions and 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

          -  Patients who received prior non-induction pembrolizumab, patients on chronic steroids
             or who have active autoimmune disease for which they received systemic treatment in
             the previous 2 years with corticosteroids, disease modifying agents, or
             immunosuppressive drugs. Replacement therapy (thyroxine, insulin or physiological
             corticosteroid replacement for adrenal or pituitary insufficiency) is allowed.
             Patients with active interstitial lung disease or who have a history of pneumonitis
             for which they had received glucocorticoids are not eligible

          -  Prior bevacizumab therapy
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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.
Safety Issue:
Description:Progression-Free Survival

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:The time it takes for disease progression to occur within the radiation treatment field of disease will be measured.
Measure:Incidence of adverse events graded per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5
Time Frame:Up to 3 years
Safety Issue:
Description:Will be reported with the frequency and severity (e.g., type, grade, and attribution) by arm.
Measure:Duration of Maintenance Chemotherapy Usage
Time Frame:Up to 3 years
Safety Issue:
Description:Will be performed on an intent to treat basis.
Measure:Time to Development of New Lesions
Time Frame:Time from randomization to the first occurrence of any new lesions that have not been treated with local consolidative therapy, assessed for up to 3 years
Safety Issue:
Description:Will be performed on an intent to treat basis.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:NRG Oncology

Last Updated