Trial Title:
Immunotherapy After Surgery for People Who Have No Remaining Cancer Cells After Standard Treatment for Early-Stage Non-Small Cell Lung Cancer, INSIGHT Trial
NCT ID:
NCT06498635
Condition:
Lung Non-Small Cell Carcinoma
Stage II Lung Cancer AJCC v8
Stage IIIA Lung Cancer AJCC v8
Stage IIIB Lung Cancer AJCC v8
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Durvalumab
Immunoglobulins
Antibodies, Monoclonal
Immunoglobulin G
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Arm I (durvalumab)
Arm group label:
Arm II (active survallence)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Arm I (durvalumab)
Arm group label:
Arm II (active survallence)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Biological
Intervention name:
Durvalumab
Description:
Given IV
Arm group label:
Arm I (durvalumab)
Other name:
Imfinzi
Other name:
Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer
Other name:
MEDI 4736
Other name:
MEDI-4736
Other name:
MEDI4736
Intervention type:
Other
Intervention name:
Patient Observation
Description:
Undergo active surveillance
Arm group label:
Arm II (active survallence)
Other name:
Active Surveillance
Other name:
deferred therapy
Other name:
expectant management
Other name:
Observation
Other name:
Watchful Waiting
Intervention type:
Other
Intervention name:
Questionnaire Administration
Description:
Ancillary studies
Arm group label:
Arm I (durvalumab)
Arm group label:
Arm II (active survallence)
Summary:
This phase III trial compares durvalumab to the usual approach (patient observation)
after surgery for the treatment of patients with early-stage non-small cell lung cancer.
Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune
system attack the cancer, and may interfere with the ability of tumor cells to grow and
spread. The usual approach for patients who are not in a study is to closely watch a
patient's condition after surgery and to have regular visits with their doctor to watch
for signs of the cancer coming back. Usually, patients do not receive further treatment
unless the cancer returns. This study will help determine whether this different approach
with durvalumab is better, the same, or worse than the usual approach of observation.
Giving durvalumab may help patients live longer and prevent early-stage non-small cell
lung cancer from coming back as compared to the usual approach.
Detailed description:
PRIMARY OBJECTIVE:
I. To compare disease free survival (DFS) in stage II-IIIB non-small cell lung cancer
participants who achieved a pathologic complete response (pCR) following standard of care
neoadjuvant chemo-immunotherapy and are randomized to adjuvant durvalumab (MEDI4736)
versus surveillance.
SECONDARY OBJECTIVES:
I. To compare the overall survival (OS) between the arms. II. To evaluate the frequency
and severity of toxicities of adjuvant durvalumab (MEDI4736).
III. To compare the event free survival (EFS) between the arms.
TRANSLATIONAL MEDICINE OBJECTIVE:
I. To bank specimens and images for additional future translational medicine studies.
QUALITY OF LIFE (QOL) PRIMARY OBJECTIVE:
I. To compare patient-reported quality of life (QOL) status between treatment arms at 6
months from randomization using the Functional Assessment of Cancer Therapy-Lung (FACT-L)
Trial Outcome Index (TOI).
QOL SECONDARY OBJECTIVES:
I. To compare patient-reported quality of life between treatment arms at 6 months from
randomization using the Functional Assessment of Cancer Therapy-Biologic Response
Modifier (FACT-BRM) physical and mental subscale scores.
II. To compare longitudinal changes in global health status between treatment arms from
randomization to 12 months using the FACT-L TOI.
PATIENT REPORTED OUTCOMES-COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS (PRO-CTCAE)
OBJECTIVE:
I. To compare participant-reported symptoms using selected PRO-CTCAE items between
treatment arms such as rash, itching, skin dryness, numbness, and tingling.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive durvalumab intravenously (IV) over 60 minutes on day 1 of each
cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease
progression or unacceptable toxicity. Patients undergo computed tomography (CT) and blood
sample collection throughout the trial.
ARM II: Patients undergo active surveillance for 12 months on study. Patients undergo CT
and blood sample collection throughout the trial.
After completion of study treatment, patients are followed up annually until 10 years
from randomization.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Participants must have histologically or cytological confirmed diagnosis of clinical
stage II-IIIB (excluding clinical N3 disease) non-small cell lung cancer (NSCLC)
- Participants must have had a (R0) resection of NSCLC (with appropriate lymph node
sampling as defined by the National Comprehensive Cancer Network [NCCN] guidelines)
within 84 days (12 weeks) prior to randomization. Acceptable types of surgical
resection are: lobectomy, sleeve resection, bi-lobectomy, or pneumonectomy. Wedge
resection is not allowed.
- Note the NCCN guidelines: N1 and N2 node resection and mapping is a routine
component of lung cancer resections. It is recommended at a minimum one N1 and
three N2 stations is sampled or complete lymph node dissection. Formal
ipsilateral mediastinal lymph node dissection is indicated for participants
undergoing resection for N2 disease
- Participants must have a pathologic complete response (pCR) (no viable tumor in the
resected specimen or lymph nodes), as determined by local pathology review
- Participants must have a PD-L1 status result (e.g. [< 1% versus >= 1% or unknown])
- Participants must not have known EGFR mutations, or ALK gene fusion
- Participants must have received at least two cycles of neoadjuvant platinum-based
chemotherapy and anti-PD-1 or anti-PD-L1 therapy. The neoadjuvant treatment must be
Food and Drug Administration (FDA) approved and standard of care as listed in NCCN
guidelines
- Participants must not be planning to receive any concurrent non-protocol directed
chemotherapy, immunotherapy, biologic or hormonal therapy for NSCLC treatment while
receiving treatment on this study
- Participants must not have received any prior systemic therapy (systemic
chemotherapy, immunotherapy or investigational drug) within 28 days prior to
randomization
- Participants must not have medical contraindications or severe adverse events to
receiving anti-PD-1 or anti-PD-L1 therapy
- Participants must not have received post-operative radiation therapy (PORT) for
NSCLC
- Participant must be ≥ 18 years old
- Participants must have body weight > 30 kg
- Participant must have Zubrod performance status of 0-2
- Participant must have a complete medical history and physical exam within 28 days
prior to randomization
- Hemoglobin > 9.0 g/dL (within 28 days prior to randomization)
- Absolute neutrophil count ≥ 1.5 x 10^3/uL (within 28 days prior to randomization)
- Platelets ≥ 100 x 10^3/uL (within 28 days prior to randomization)
- Total bilirubin ≤ 1 x institutional upper limit of normal (ULN) unless history of
Gilbert's disease. Participants with history of Gilbert's disease must have total
bilirubin ≤ 5 x institutional ULN (within 28 days prior to randomization)
- Aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 3 × institutional ULN
(within 28 days prior to randomization)
- Participants must have a creatinine ≤ 1.5x the institutional upper limit of normal
(IULN) OR measured OR calculated creatinine clearance ≥ 40 mL/min using the
following Cockcroft-Gault Formula. This specimen must have been drawn and processed
within 28 days prior to randomization
- Participants must have fully recovered from the effects of prior surgery in the
opinion of the treating investigator
- Participants with a known history of human immunodeficiency virus (HIV)-infection
must be on effective anti-retroviral therapy at registration and have undetectable
viral load test on the most recent test results obtained within 6 months prior to
randomization
- Participants with a known history of chronic hepatitis B virus (HBV) infection must
have undetectable HBV viral load while on suppressive therapy on the most recent
test results obtained within 6 months prior to randomization, if indicated
- Participants with a known history of hepatitis C virus (HCV) infection must have
been treated and cured. Participants currently being treated for HCV infection must
have undetectable HCV viral load test on the most recent test results obtained
within 6 months prior to randomization, if indicated
- Participants must not have had an organ transplant
- Participants must not have a prior or concurrent malignancy whose natural history or
treatment (in the opinion of the treating physician) has the potential to interfere
with the safety or efficacy assessment of the investigational regimen
- Participant must not have medical contraindications to receiving immunotherapy,
including history of non-infectious pneumonitis that required steroids or active
autoimmune disease that has required systemic treatment with disease modifying
agents, corticosteroids or immunosuppressive drugs in the past two years.
Replacement therapy (e.g. thyroxine for pre-existing hypothyroidism, insulin for
type I diabetes mellitus, or physiologic corticosteroid replacement therapy for
adrenal or pituitary insufficiency, etc.) is not considered a form of systemic
treatment. Intra-articular steroid injections are allowed
- Participants must not be pregnant or nursing (nursing includes breast milk fed to an
infant by any means, including from the breast, milk expressed by hand, or pumped).
Individuals who are of reproductive potential must have agreed to use an effective
contraceptive method during protocol therapy and for 6 months following completion
of protocol therapy with details provided as a part of the consent process. A person
who has had menses at any time in the preceding 12 consecutive months or who has
semen likely to contain sperm is considered to be of "reproductive potential." In
addition to routine contraceptive methods, "effective contraception" also includes
refraining from sexual activity that might result in pregnancy and surgery intended
to prevent pregnancy (or with a side-effect of pregnancy prevention) including
hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and
vasectomy with testing showing no sperm in the semen. Participants should not
breastfeed during protocol therapy and for 6 months following completion of protocol
therapy
- Participants must not have received a live or live attenuated vaccine within 28 days
prior randomization. Examples of live vaccines include, but are not limited to, the
following: measles, mumps, rubella, varicella/zoster, yellow fever rabies, Bacillus
Calmette-Guerin (BCG) and typhoid vaccine. Seasonal influenza vaccines and COVID-19
vaccines are allowed, however, intranasal influenza vaccines (e.g. Flu-Mist) are
live attenuated, and are not allowed
- Participants must be offered the opportunity to participate in specimen banking
- Participants who can complete FACT-L, FACT-BRM, and PRO-CTCAE questionnaires forms
in English, or Spanish must agree to participate in the patient-reported outcome
study
- NOTE: 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
- Participants must be informed of the investigational nature of this study and must
sign and give informed consent in accordance with institutional and federal
guidelines
- For participants with impaired decision-making capabilities, legally authorized
representatives may sign and give informed consent on behalf of study participants
in accordance with applicable federal, local, and Central Institutional Review Board
(CIRB) regulations
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
March 14, 2025
Completion date:
July 15, 2039
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Cancer Institute (NCI)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06498635
