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 with newly diagnosed, de novo American Joint Committee on Cancer (AJCC)
             eighth edition stage 4 metastatic non-small cell lung cancer (NSCLC)

          -  Pathologic diagnosis of non-small cell lung cancer prior to enrollment

          -  Patients can be registered on study prior to or during systemic chemotherapy. Only
             those with at least stable disease, no new sites of disease, and all known metastatic
             lesions amenable to local radiotherapy will be eligible for randomization

          -  Maximum number of sites per patient will be eight total at time of enrollment, with
             the primary and or regional lymph nodes counting together as one site and any central
             nervous system (CNS) disease treated with stereotactic radiation counted as 1 site. A
             patient may have multiple brain lesions, but as long as they are treated with
             stereotactic radiosurgery (SRS) these will cumulatively be considered as one site.
             Brain lesions may be treated with SRS prior to randomization. Organ-specific limits
             apply as below.

          -  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.

        Lung:

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

        Primary site:

          -  T1-2N0 primary lesions may also be treated with stereotactic body radiation therapy
             (SBRT)

          -  T1-4N1-3 disease may be treated with radiation therapy using 2 to 7 weeks of daily
             radiotherapy with or without concurrent chemoradiation at the discretion of the
             treating clinician, however they must be able to anticipate meeting applicable
             dosimetric guidelines

          -  Performance status 0-2 (Eastern Cooperative Oncology Group [ECOG]) at randomization

          -  A signed study specific consent form is required

        Patient must have normal organ and marrow function as defined below:

          -  Leukocytes >= 3,000/mcL

          -  Absolute neutrophil count >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Total bilirubin within normal institutional limits

          -  Aspartate aminotransferase (ALT) (serum glutamic-oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 X institutional upper limit of normal

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

        Exclusion Criteria:

          -  Patients with a history of prior radiation to the sites involved.

          -  Patients with the targetable mutations EGFR or ALK.

          -  Pregnant or lactating women.

          -  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 1 breast cancer, non-invasive bladder cancer, or treated in-situ cervical
             cancer).
      
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

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