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.
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
Drug | Synonyms | Arms |
---|
Atezolizumab | MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, Tecentriq | Treatment (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
Name | Type | Description | Interventions |
---|
Treatment (hypofractionated radiation therapy, atezolizumab) | Experimental | 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 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. | |
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
Registration Step 1. 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: Patients 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. Patient must have an HCV antibody test within 28 days
prior to Registration Step 1. If the HCV antibody test is positive, the patient must
also have an HCV quantitative RNA test within 28 days prior to Registration Step 1
- 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
August 25, 2021