Clinical Trial: NCT03867175 - My Cancer Genome

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

URL:

https://clinicaltrials.gov/show/NCT03867175

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

Drug	Synonyms	Arms
Pembrolizumab	Keytruda, Lambrolizumab, MK-3475, SCH 900475	Arm 1 Stereotactic Body Radiation Therapy/Pembrolizumab

Purpose

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

Name	Type	Description	Interventions
Arm 1 Stereotactic Body Radiation Therapy/Pembrolizumab	Experimental	3-10 treatments of SBRT/ pembrolizumab IV for 30 minutes every 3-4 weeks for 1 year at doctor's discretion.	Pembrolizumab
Arm 2 Pembrolizumab	Experimental	Patients 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

          -  Performance Status 0-2 (ECOG) at time of consult with radiation oncology

          -  Pathologically proven nonsmall cell lung cancer with evidence of metastatic disease.

          -  Must have received 4 cycles of standard combination chemo-immunotherapy, with a CT
             chest abdomen pelvis that was performed after completion of these 4 cycles and
             demonstrates no evidence of progression per RECIST v1.1

          -  To be eligible for enrollment and randomization, patients must be within 180 days from
             their first dose of combination chemo-immunotherapy. Cycle 1 day 1 is defined as day
             1. If enrolled on day 180, the patient would need to be randomized the same day.

          -  Persistent active disease must be amenable to radiation treatment per the treating
             radiation oncologist, and patients must have at least one residual site of disease
             which can be identified by CT or PET/CT and targeted with radiation.

          -  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 they meet
             all criteria above.

          -  There are no strict size or tumor number limitations in a given organ (lung, liver,
             abdomen pelvis, or spine). This is at the discretion of the treating radiation
             oncologist.

        Exclusion Criteria from Enrollment

          -  More than 180 days has elapsed since day 1 of cycle 1 of combination
             chemo-immunotherapy.

          -  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 now with oligometastatic
             recurrence 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

        Eligibility for Randomization

          -  Once enrolled on study, patients will have a PET/MRI brain for restaging. Patients
             with no evidence of progression and 8 or fewer sites of active persistent disease per
             the treating physician are eligible for randomization.

          -  If a PET has been performed within 30 days of enrollment with no evidence of
             progression per RECIST v1.1, then this scan may be used and does not have to be
             repeated prior to randomization

          -  If an MRI brain has been performed within 90 days of enrollment with no evidence of
             progression per RECIST v1.1, then this scan may be used and does not have to be
             repeated prior to randomization

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

October 5, 2020

Clinical Trials /

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