Clinical Trials /

Study of Radiation Therapy Followed by Atezolizumab in Stage II or III Non-small Cell Lung Cancer Patients

NCT04310020

Description:

This trial studies the side effects of radiation therapy followed by atezolizumab in treating patients with stage II or III non-small cell lung cancer. Hyperfractionated radiation therapy delivers smaller doses of radiation therapy over time and may kill more tumor 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.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Radiation Therapy Followed by Atezolizumab in Stage II or III Non-small Cell Lung Cancer Patients
  • Official Title: A Pilot Study of Hypofractionated Radiotherapy Followed by Atezolizumab Consolidation in Stage II or III NSCLC Patients With Borderline Performance Status

Clinical Trial IDs

  • ORG STUDY ID: NCI-2020-01543
  • SECONDARY ID: NCI-2020-01543
  • SECONDARY ID: S1933
  • SECONDARY ID: S1933
  • SECONDARY ID: U10CA180888
  • NCT ID: NCT04310020

Conditions

  • Recurrent Lung Non-Small Cell Carcinoma
  • Stage II Lung Cancer AJCC v8
  • Stage IIA Lung Cancer AJCC v8
  • Stage IIB Lung Cancer AJCC v8
  • Stage III Lung Cancer AJCC v8
  • Stage IIIA Lung Cancer AJCC v8
  • Stage IIIB Lung Cancer AJCC v8
  • Stage IIIC Lung Cancer AJCC v8
  • Unresectable Lung Non-Small Cell Carcinoma

Interventions

DrugSynonymsArms
AtezolizumabMPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, TecentriqTreatment (hypofractionated radiation therapy, atezolizumab)

Purpose

This trial studies the side effects of radiation therapy followed by atezolizumab in treating patients with stage II or III non-small cell lung cancer. Hyperfractionated radiation therapy delivers smaller doses of radiation therapy over time and may kill more tumor 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.

Detailed Description

      PRIMARY OBJECTIVE:

      I. To evaluate the rate of grade 3-5 treatment-related adverse events (TRAEs) in patients who
      are not candidates for surgery or concurrent chemoradiation and who have either performance
      status 0-2 and stage II or performance status 2 and stage III non-small cell lung cancer
      (NSCLC), treated with hypofractionated thoracic radiotherapy followed by atezolizumab.

      SECONDARY OBJECTIVES:

      I. To evaluate response rate (confirmed and unconfirmed, complete and partial by Response
      Evaluation Criteria in Solid Tumors [RECIST] 1.1) from Registration Step 2 in the subset of
      patients with measurable disease.

      II. To evaluate response rate (confirmed and unconfirmed, complete and partial by RECIST 1.1)
      during radiation therapy in the subset of patients with measurable disease.

      III. To evaluate progression free survival (PFS) from Registration Step 2 by RECIST 1.1.

      IV. To evaluate overall survival (OS) from Registration Step 2. V. To evaluate the frequency
      and severity of toxicities.

      ADDITIONAL OBJECTIVE:

      I. To bank blood and archival tissue for future research.

      OUTLINE:

      RADIATION THERAPY: Patients undergo hypofractionated radiation therapy 5 days per week for 3
      weeks in the absence of disease progression or unacceptable toxicity.

      CONSOLIDATION: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1.
      Cycles repeat every 21 days for up to 12 months (maximum of 17 cycles) in the absence of
      disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 6 weeks, every 12 months for
      the 1 year, then every 6 months until 3 years after study start.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (hypofractionated radiation therapy, atezolizumab)ExperimentalRADIATION THERAPY: Patients undergo hypofractionated radiation therapy 5 days per week for 3 weeks in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients receive atezolizumab IV over 30-60 minutes on day 1. Cycles repeat every 21 days for up to 12 months (maximum of 17 cycles) in the absence of disease progression or unacceptable toxicity.
  • Atezolizumab

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 computed tomography (CT) or magnetic resonance imaging (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 50% 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 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
             randomization. Patient must not have active (chronic or acute) hepatitis B virus (HBV)
             infection. Patients may have past or resolved HBV infection. Active HBV is defined as
             having a positive hepatitis B surface antigen (HBsAg) test. Past or resolved HBV is
             defined as having a negative HBsAG test and a positive total hepatitis B core antibody
             (HBcAb) test

          -  REGISTRATION STEP 1: Patient must be tested for hepatitis C within 28 days prior to
             randomization. Patient must not have active hepatitis C virus (HCV) infection. Active
             HCV is defined as having a positive HCV antibody test followed by a positive HCV
             ribonucleic acid (RNA) test

          -  REGISTRATION STEP 1: No other prior malignancy is allowed except for the following:
             adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer,
             adequately treated Stage I or II cancer from which the patient is currently in
             complete remission, or any other cancer from which the patient has been disease free
             for three years. Participants with localized prostate cancer who are being followed by
             an active surveillance program are also eligible

          -  REGISTRATION STEP 1: Participants must be offered optional participation in banking of
             specimens for future research

          -  REGISTRATION STEP 1: Participants must be informed of the investigational nature of
             this study and must sign and give written informed consent in accordance with
             institutional and federal guidelines

          -  REGISTRATION STEP 1: As a part of the Oncology Patient Enrollment Network (OPEN)
             registration process the treating institution's identity is provided in order to
             ensure that the current (within 365 days) date of institutional review board approval
             for this study has been entered in the system

          -  REGISTRATION STEP 2: Participants must be registered to Step 2 within 42 days after
             completion of radiation treatment. Participants must have received at least 44 Gy of
             radiation treatment

          -  REGISTRATION STEP 2: Participants must have no evidence of progression per RECIST 1.1
             on CT scan of the chest, abdomen, and pelvis performed between 2 and 5 weeks after
             completion of radiation therapy

          -  REGISTRATION STEP 2: Any toxicities from radiation therapy must have resolved to <
             grade 2

          -  REGISTRATION STEP 2: Absolute neutrophil count (ANC) >= 1500/mcl (obtained within 28
             days prior to Registration Step 2)

          -  REGISTRATION STEP 2: Platelet count >= 100,000/mcl (obtained within 28 days prior to
             Registration Step 2)

          -  REGISTRATION STEP 2: Hemoglobin >= 9 grams/dL (obtained within 28 days prior to
             Registration Step 2)

          -  REGISTRATION STEP 2: Total bilirubin =< 1.5 x institutional upper limit of normal
             (IULN) (obtained within 28 days prior to Registration Step 2)

          -  REGISTRATION STEP 2: AST and ALT =< 2.5 x IULN (obtained within 28 days prior to
             Registration Step 2)

          -  REGISTRATION STEP 2: Serum creatinine =< 1.5 x IULN OR measured or calculated
             creatinine clearance >= 40 mL/min (obtained within 28 days prior to Registration Step
             2)

          -  REGISTRATION STEP 2: Participants must not have received steroids in doses of more
             than prednisone 10 mg daily or equivalent within 14 days prior to Registration Step 2

          -  REGISTRATION STEP 2: Participants must not have received a live vaccine within 28 days
             prior to Registration Step 2
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of grade 3-5 adverse events
Time Frame:From baseline, until 180 days from Step 2 registration
Safety Issue:
Description:Individual toxicities with possible, probable or likely attribution to treatment along with the overall rate of grade 3, 4 or 5 toxicities attributable to treatment will be summarized.

Secondary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to 3 years
Safety Issue:
Description:Individual toxicities with possible, probable or likely attribution to treatment along with the overall rate of grade 3, 4 or 5 toxicities attributable to treatment will be summarized.
Measure: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)
Time Frame:After atezolizumab treatment
Safety Issue:
Description:Binary endpoints will be summarized as proportions with 95% Clopper-Pearson confidence intervals.
Measure:Response rate (confirmed and unconfirmed, complete and partial by RECIST 1.1) in the subset of patients with measurable disease (Registration Step 1)
Time Frame:During radiation therapy
Safety Issue:
Description:Binary endpoints will be summarized as proportions with 95% Clopper-Pearson confidence intervals.
Measure:Progression-free survival
Time Frame: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
Safety Issue:
Description:Estimated using the method of Kaplan-Meier. 95% confidence for the medians will be constructed using the method of Brookmeyer-Crowley.
Measure:Overall survival
Time Frame:From date of Step 2 registration to date of death due to any cause, assessed up to 3 years
Safety Issue:
Description:Estimated using the method of Kaplan-Meier. 95% confidence for the medians will be constructed using the method of Brookmeyer-Crowley.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

Last Updated

July 8, 2020