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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03867175
Recruitment Status : Recruiting
First Posted : March 7, 2019
Last Update Posted : June 29, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Wake Forest University Health Sciences

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Metastatic Lung Cancer Stage IV Lung Cancer Radiation: Stereotactic Body Radiation Therapy Biological: Pembrolizumab Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 112 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 24, 2019
Estimated Primary Completion Date : July 31, 2027
Estimated Study Completion Date : December 31, 2027

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm 1 Stereotactic Body Radiation Therapy/Pembrolizumab
3-10 treatments of SBRT/ pembrolizumab IV for 30 minutes every 3-4 weeks for 1 year at doctor's discretion.
Radiation: Stereotactic Body Radiation Therapy
Patients undergo 3-10 treatments of stereotactic body radiation therapy (SBRT)
Other Name: Stereotactic Ablative Body Radiation Therapy

Biological: Pembrolizumab
Patients undergo 3-10 treatments of SBRT. Patients also receive pembrolizumab IV over 30 minutes every 3-4 weeks for 1 year at the discretion of the treating physician.
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475

Experimental: Arm 2 Pembrolizumab
Patients receive pembrolizumab IV over 30 minutes every 3-4 weeks for 1 year at the discretion of the treating physician.
Biological: Pembrolizumab
Patients undergo 3-10 treatments of SBRT. Patients also receive pembrolizumab IV over 30 minutes every 3-4 weeks for 1 year at the discretion of the treating physician.
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475




Primary Outcome Measures :
  1. Progression-free survival (PFS) after completion of first line systemic therapy [ Time Frame: Up to 5 years ]
    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 :
  1. Overall Survival [ Time Frame: Up to 5 years ]
    Will be reported with an exact 95% confidence interval.

  2. Time of Progression [ Time Frame: Baseline up to 5 years ]
    In patients not receiving radiation, the investigators will assess progression at their known sites of disease prior to beginning first line systemic chemotherapy.

  3. Rate of Failure [ Time Frame: Baseline up to 5 years ]
    Investigators will assess the rate of failures inside and outside of radiation treatment.

  4. Number of Participants with New Sites of Disease [ Time Frame: Baseline up to 5 years ]
    Investigators will assess the development of new sites of disease during or after immunotherapy

  5. Incidence of adverse events [ Time Frame: Up to 5 years ]
    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.



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 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.

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): NCT03867175


Contacts
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Contact: Sharon Averill, RN 336-713-7748 saverill@wakehealth.edu

Locations
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United States, North Carolina
Wake Forest Baptist Comprehensive Cancer Center Recruiting
Winston-Salem, North Carolina, United States, 27157
Principal Investigator: Michael Farris, MD         
Sponsors and Collaborators
Wake Forest University Health Sciences
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Michael Farris, MD Wake Forest University Health Sciences
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Responsible Party: Wake Forest University Health Sciences
ClinicalTrials.gov Identifier: NCT03867175    
Other Study ID Numbers: IRB00056681
NCI-2019-01259 ( Other Identifier: Clinical Trial Reporting Program )
CCCWFU 62718 ( Other Identifier: Wake Forest Baptist Comprehensive Cancer Center )
P30CA012197 ( U.S. NIH Grant/Contract )
First Posted: March 7, 2019    Key Record Dates
Last Update Posted: June 29, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents