Clinical Trials /

Immunotherapy With or Without SBRT in Patients With Stage IV Non-small Cell Lung Cancer

NCT03867175

Description:

This phase III trial studies immunotherapy and stereotactic body radiation therapy to see how well it works compared with immunotherapy alone after first-line systemic therapy (therapy that goes throughout the body) in treating patients with stage IV non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving immunotherapy with stereotactic body radiation therapy may work better than immunotherapy alone in treating patients with non-small cell lung cancer.

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

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Immunotherapy With or Without SBRT in Patients With Stage IV Non-small Cell Lung Cancer
  • Official Title: A Randomized Trial of Consolidative Immunotherapy With vs Without Thoracic Radiotherapy and / or Stereotactic Body Radiation Therapy (SBRT) After First-Line Systemic Therapy for Metastatic NSCLC

Clinical Trial IDs

  • ORG STUDY ID: IRB00056681
  • SECONDARY ID: NCI-2019-01259
  • SECONDARY ID: CCCWFU 62718
  • SECONDARY ID: P30CA012197
  • NCT ID: NCT03867175

Conditions

  • Metastatic Lung Cancer
  • Stage IV Lung Cancer

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Arm 1 Stereotactic Body Radiation Therapy/Pembrolizumab

Purpose

This phase III trial studies immunotherapy and stereotactic body radiation therapy to see how well it works compared with immunotherapy alone after first-line systemic therapy (therapy that goes throughout the body) in treating patients with stage IV non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving immunotherapy with stereotactic body radiation therapy may work better than immunotherapy alone in treating patients with non-small cell lung cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To compare progression-free survival of patients randomized to radiation and consolidative
      immunotherapy against those receiving consolidative immunotherapy alone.

      SECONDARY OBJECTIVES:

      I. To estimate overall survival in all patients and will compare overall survival of those
      randomized to radiation and consolidative immunotherapy against those receiving consolidative
      immunotherapy alone.

      II. In patients receiving radiation, to describe the rate of in-field local control and rate
      of out-of-field disease progression with serial imaging.

      III. In patients not receiving radiation, describe progression at known sites of disease
      after first line systemic therapy and rate of development of new metastases with serial
      imaging.

      IV. To evaluate toxicity associated with radiation followed by consolidative immunotherapy.

      OUTLINE: Patients are randomized to 1 of 2 arms.

      ARM I: Patients undergo 3-10 treatments of stereotactic body radiation therapy (SBRT).
      Patients also receive pembrolizumab intravenously (IV) over 30 minutes every 3-4 weeks for 1
      year at the discretion of the treating physician.

      ARM II: Patients receive pembrolizumab IV over 30 minutes every 3-4 weeks for 1 year at the
      discretion of the treating physician.

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

Trial Arms

NameTypeDescriptionInterventions
Arm 1 Stereotactic Body Radiation Therapy/PembrolizumabExperimental3-10 treatments of SBRT/ pembrolizumab IV for 30 minutes every 3-4 weeks for 1 year at doctor's discretion.
  • Pembrolizumab
Arm 2 PembrolizumabExperimentalPatients receive pembrolizumab IV over 30 minutes every 3-4 weeks for 1 year at the discretion of the treating physician.
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients who are 18 years or older.

          -  Pathologically proven non-small cell lung cancer with evidence of metastatic disease

          -  Must have received 4 cycles of standard of care chemo-immunotherapy and have no
             evidence of disease progression at time of restaging with PET and MRI brain.

          -  Metastatic lesions must be amenable to local radiotherapy per treating radiation
             oncologist.

          -  Patients who previously had earlier stage NSCLC treated definitively and have now
             developed new distant disease, are eligible for inclusion if they have undergone at
             least 4 cycles of chemo-immunotherapy for their metastatic recurrence and restaging
             demonstrates no evidence of progression.

          -  The maximum number of residual sites of disease will be eight total at time of
             enrollment.

          -  Patients must have at least one residual site of disease which can be identified by CT
             or PET/CT.

          -  The primary and or regional lymph nodes will count together as one site and any number
             of CNS lesions treated with stereotactic radiation will be cumulatively counted as 1
             site. Treatment of CNS disease with stereotactic radiosurgery may take place prior to
             completion of first line chemotherapy. However, if CNS disease was treated prior to
             systemic therapy this will still be counted as 1 site of disease at time of
             randomization.

          -  Patients may have a history of prior radiation, however the treating radiation
             oncologist must assess prior to enrollment to ensure that reasonable dosimetric
             constraints can be met.

          -  There are no strict size or tumor number limitations in lung, liver, abdomen pelvis,
             or spine organ sites, however the treating radiation oncologist must agree that
             dosimetric constraints are likely to be respected if all known sites of disease remain
             stable following line systemic therapy.

          -  Patients with two lung lesions determined by the treating clinician to be synchronous
             early-stage primary cancers will not be eligible.

          -  T1-4N1-3 disease may be treated with more fractionated (non-SBRT) radiation therapy
             using 2 to 7 weeks of daily radiotherapy with or without concurrent chemoradiation if
             the treatment site cannot be safely treated with SBRT. This decision is at the
             discretion of the treating radiation oncologist.

          -  Performance Status 0-2 (ECOG) at Randomization

          -  A signed study specific consent form is required.

          -  Patients must have normal organ and marrow function as defined below:

          -  Leukocytes greater than or equal to 3,000/mcL

          -  Absolute neutrophil count greater than or equal to 1,500/mcL

          -  Platelets greater than or equal to 100,000/mcL

          -  Total bilirubin within normal institutional limits

          -  AST(SGOT)/ALT(SGPT) less than or equal to 2.5 X institutional upper limit of normal

          -  Creatinine - within normal institutional limits OR creatinine clearance greater than
             60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.

        Exclusion Criteria:

          -  Pregnant or lactating women.

          -  The patient has received treatment for other carcinomas within the last three years
             (Except for cured non-melanoma skin cancer, low-risk prostate cancer, T1/T2 glottic
             cancer, stage 0 or stage I breast cancer, non-invasive bladder cancer, or treated
             in-situ cervical cancer). Prior lung cancer diagnosis is not an exclusion criteria.

          -  Patients with major activating mutations in EGFR (del19, L858R, and T790M) or ROS 1 or
             ALK gene rearrangements are excluded.

          -  Patients with two lung lesions determined by the treating clinician to be synchronous
             early-stage primary cancers will not be eligible.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS) after completion of first line systemic therapy
Time Frame:Up to 5 years
Safety Issue:
Description:Will be determined using the product-limit method of Kaplan and Meier. Will compare unadjusted median PFS between the 2 arms using a log-rank test. Will also use a proportional hazards model to compare progression-free survival between the two groups, adjusting for key covariates such as age, performance (Eastern Cooperative Oncology Group) status, response to initial systemic therapy versus (vs) stable disease, the presence or absence of brain metastases, PD-L1 [programmed death-ligand ] expression (< 1% vs > 50%), tumor histology (adenocarcinoma vs non-adenocarcinoma), and number of disease sites treated (1-3 sites vs 4-6 sites).

Secondary Outcome Measures

Measure:Overall Survival
Time Frame:Up to 5 years
Safety Issue:
Description:Will be reported with an exact 95% confidence interval.
Measure:Time of Progression
Time Frame:Baseline up to 5 years
Safety Issue:
Description:In patients not receiving radiation, the investigators will assess progression at their known sites of disease prior to beginning first line systemic chemotherapy.
Measure:Rate of Failure
Time Frame:Baseline up to 5 years
Safety Issue:
Description:Investigators will assess the rate of failures inside and outside of radiation treatment.
Measure:Number of Participants with New Sites of Disease
Time Frame:Baseline up to 5 years
Safety Issue:
Description:Investigators will assess the development of new sites of disease during or after immunotherapy
Measure:Incidence of adverse events
Time Frame:Up to 5 years
Safety Issue:
Description:All safety measures, including acute and late toxicity, will be reported using descriptive statistics (mean, median, standard deviation, proportions, and 95% confidence intervals). This will include calculating frequency/risk of adverse events by treatment site. Potential toxicities reported would include pneumonitis, esophagitis, chest wall pain, dermatologic toxicity, renal dysfunction, gastrointestinal toxicity including nausea, vomiting, and diarrhea, hepatotoxicity, and abdominal pain. These toxicities would be assessed according to site of irradiation by the treating physician and graded as per Common Terminology Criteria for Adverse Events 5.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Wake Forest University Health Sciences

Last Updated

December 3, 2019