A Pilot Study of Hypofractionated Radiotherapy Followed by Atezolizumab Consolidation in Stage II or III NSCLC Patients With Borderline Performance Status

Plain English Summary

Study of Radiation Therapy Followed by Atezolizumab in Stage II or III Non-small Cell Lung Cancer Patients is a Phase 2 clinical trial sponsored by National Cancer Institute (NCI) studying Lung Non-Small Cell Carcinoma, Stage II Lung Cancer AJCC v8, Stage III Lung Cancer AJCC v8. This study tests a combination of radiation therapy and a drug called atezolizumab for patients with stage II or III non-small cell lung cancer. It is for patients with non-small cell lung cancer who are not candidates for surgery or standard chemotherapy with radiation. Participation involves receiving a shorter, higher dose of radiation therapy followed by atezolizumab infusions, with regular check-ups and tests. Alternative treatments may include surgery, chemotherapy, or standard radiation therapy, depending on the cancer stage and patient's health. The trial aims to enroll 47 participants.

Official Summary

This phase II trial studies the side effects of radiation therapy followed by atezolizumab in treating patients with stage II or III non-small cell lung cancer. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more cancer cells and have fewer side effects. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The purpose of this study is to test the safety and effectiveness of radiation therapy followed by atezolizumab and find out what side effects, if any, it has on patient's non-small cell lung cancer.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients with stage II or III non-small cell lung cancer who are not eligible for surgery or standard chemoradiation. Must have a performance status of 0-2 for stage II or 2 for stage III lung cancer. Must have measurable or non-measurable disease and meet specific blood count, organ function, and lung capacity requirements. Cannot have active autoimmune disease or certain types of lung inflammation (pneumonitis). This trial is studying Lung Non-Small Cell Carcinoma, Stage II Lung Cancer AJCC v8, Stage III Lung Cancer AJCC v8, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures the rate of serious side effects (grade 3-5) from the treatment, indicating how safe the combination therapy is. The specific primary outcome measures are: Rate of grade 3-5 adverse events (From baseline, until 180 days from Step 2 registration). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a need for new treatments for patients with advanced lung cancer who cannot undergo standard surgical or chemoradiation options, by combining radiation with immunotherapy. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Lung Non-Small Cell Carcinoma, Stage II Lung Cancer AJCC v8, Stage III Lung Cancer AJCC v8, where improved treatment options are needed.

Investor Insight

This phase II study explores a novel combination for a significant patient population in non-small cell lung cancer, potentially paving the way for larger trials and future treatment standards. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if this treatment is suitable for your specific type and stage of lung cancer. Understand the schedule of radiation sessions and atezolizumab infusions, and any travel required for treatment. Be prepared for regular blood tests, scans, and doctor visits to monitor your health and response to treatment. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 47 participants

Interventions

• DRUG: Atezolizumab — Given IV
• PROCEDURE: Biospecimen Collection — Undergo blood sample collection
• PROCEDURE: Computed Tomography — Undergo CT scan
• RADIATION: Hypofractionated Radiation Therapy — Undergo hypofractionated radiation therapy
• PROCEDURE: Magnetic Resonance Imaging — Undergo MRI

Primary Outcomes

• Rate of grade 3-5 adverse events (From baseline, until 180 days from Step 2 registration)

Secondary Outcomes

• Incidence of adverse events (Up to 3 years)
• Response rate (confirmed and unconfirmed, complete and partial by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) in the subset of patients with measurable disease (Registration Step 2) (After atezolizumab treatment)
• Response rate (confirmed and unconfirmed, complete and partial by RECIST 1.1) in the subset of patients with measurable disease (Registration Step 1) (During radiation therapy)
• Progression-free survival (From date of Step 2 registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 3 years)
• Overall survival (From date of Step 2 registration to date of death due to any cause, assessed up to 3 years)

Full Eligibility Criteria

Inclusion Criteria:

* REGISTRATION STEP 1: Participants must have pathologic (cytological or histological) proof of non-small cell lung cancer (NSCLC)
* REGISTRATION STEP 1: Participants must have stage III NSCLC with Zubrod performance status of 2 or stage II NSCLC with Zubrod performance status of 0-2
* REGISTRATION STEP 1: Participants must not be candidates for surgical resection in the opinion of the treating investigator. Participants whose disease was previously resected must have experienced local or regional recurrence at least 12 months after resection
* REGISTRATION STEP 1: Participants must not be candidates for concurrent chemoradiation in the opinion of the treating investigator
* REGISTRATION STEP 1: Participants must have measurable or non-measurable disease documented by CT or MRI. Measurable disease must be assessed within 28 days prior to Registration Step 1. Non-measurable disease must be assessed within 42 days prior to Step 1 registration. The CT from a combined positron emission tomography (PET)/CT may be used only if it is of diagnostic quality. All known sites of disease must be assessed and documented on the Baseline Tumor Assessment Form (RECIST 1.1)
* REGISTRATION STEP 1: Participants must have an MRI or CT scan of the brain with contrast within 28 days prior to Registration Step 1
* REGISTRATION STEP 1: Participants' disease must fit within the radiation constraints in the opinion of a local radiation oncologist
* REGISTRATION STEP 1: Participants may have received prior treatment for their lung cancer, including surgery, chemotherapy, targeted agents, and/or radiation treatment. At least 12 months must have elapsed since last treatment
* REGISTRATION STEP 1: Participants may have had prior radiation therapy as long as the irradiated area does not overlap with the radiation field targeted for this study
* REGISTRATION STEP 1: Participants must have recovered from any adverse effects of prior major surgery to the satisfaction of the treating physician. Biopsies and central IV access placement are not considered major surgery
* REGISTRATION STEP 1: Absolute neutrophil count (ANC) \>= 1500/mcl (obtained within 28 days prior to Registration Step 1)
* REGISTRATION STEP 1: Platelet count \>= 100,000/mcl (obtained within 28 days prior to Registration Step 1)
* REGISTRATION STEP 1: Hemoglobin \>= 9 grams/dL (obtained within 28 days prior to Registration Step 1)
* REGISTRATION STEP 1: Total bilirubin =\< 1.5 x institutional upper limit of normal (IULN) (obtained within 28 days prior to Registration Step 1)
* REGISTRATION STEP 1: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x IULN (obtained within 28 days prior to Registration Step 1)
* REGISTRATION STEP 1: Serum creatinine =\< 1.5 x IULN OR measured or calculated creatinine clearance \>= 40 mL/min (obtained within 28 days prior to Registration Step 1)
* REGISTRATION STEP 1: Participants must have percent predicted diffusing capacity of the lungs for carbon monoxide (DLCO) of at least 40% documented within 90 days prior to Registration Step 1
* REGISTRATION STEP 1: Patient must not have had a prior history of interstitial lung disease or \> grade 2 (Common Terminology Criteria for Adverse Events \[CTCAE\] version 5) pneumonitis
* REGISTRATION STEP 1: Participants must not have active autoimmune disease requiring therapy within the past 6 months
* REGISTRATION STEP 1: Participants must not have an active infection requiring therapy
* REGISTRATION STEP 1: Participants must be ≥ 18 years old
* REGISTRATION STEP 1: Participants must not be pregnant or nursing because atezolizumab has not been studied in pregnant or nursing women and the mechanism of action is expected to cause fetal harm. Women/men of reproductive potential must have agreed to use an effective contraceptive method while on protocol treatment and for five months after last dose of atezolizumab. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
* REGISTRATION STEP 1: Participants with known human immunodeficiency virus (HIV) infection must be on effective anti-retroviral therapy and must have undetectable viral load at their most recent viral load test and within 6 months prior to Registration Step 1
* REGISTRATION STEP 1: Patient must be tested for hepatitis B within 28 days prior to Registration Step 1. Patient must not have active (chronic or acute) hepatitis B

Trial Locations

• University of Alabama at Birmingham Cancer Center, Birmingham, Alabama, United States
• Anchorage Associates in Radiation Medicine, Anchorage, Alaska, United States
• Alaska Breast Care and Surgery LLC, Anchorage, Alaska, United States
• Alaska Oncology and Hematology LLC, Anchorage, Alaska, United States
• Alaska Women's Cancer Care, Anchorage, Alaska, United States
• Katmai Oncology Group, Anchorage, Alaska, United States
• Providence Alaska Medical Center, Anchorage, Alaska, United States
• NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro, Jonesboro, Arkansas, United States
• University of California Davis Comprehensive Cancer Center, Sacramento, California, United States
• AdventHealth Porter, Denver, Colorado, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Lung Cancer
• Non-Small Cell Lung Cancer
• Stage II Lung Cancer
• Stage III Lung Cancer
• Thoracic Oncology
• Radiation Oncology
• Medical Oncology
• Immunotherapy
• Lung Tumors
• Cancer Treatment

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