Lung Non-Squamous Non-Small Cell CarcinomaNCT04954885
Evaluating Modifiable Biomarkers for the Prediction of Immunotherapy Response and Toxicity
An observational study of Lung Non-Squamous Non-Small Cell Carcinoma and Stage IIIB Lung Cancer AJCC v8, run by Ohio State University Comprehensive Cancer Center at 1 site in United States.
Trial summary
This study evaluates gut microbiome and functional status as modifiable biomarkers in predicting immunotherapy response and toxicity in patients with stage IV non-squamous non-small cell lung cancer receiving pembrolizumab alone or in combination with pemetrexed and carboplatin on the INSIGNIA trial. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Non-Squamous Non-Small Cell Carcinoma, Stage IIIB Lung Cancer AJCC v8, Stage IV Lung Cancer AJCC v8
- What is being tested?
- Biospecimen Collection, Physical Performance Testing and Questionnaire Administration
- Type of treatment
- Surgery or procedure
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 18 May 2021to 12 Oct 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Individuals who received randomized treatment from the INSIGNA protocol
Who may be able to join
- Histologically or cytologically confirmed stage IV non-squamous non-small cell lung cancer (NSCLC) (includes M1a, M1b stage disease, and American Joint Committee on Cancer (AJCC) 7th edition. Patients with T4NX disease (stage IIIB) with nodule in ipsilateral lung lobe are eligible if they are not candidates for combined chemotherapy and radiation.
- Formalin-fixed paraffin-embedded tumor tissue from a procedure performed within 6 months prior to registration is available for submission following registration. Formalin-fixed paraffin-embedded tumor tissue within six months of randomization available for analysis.
- PD-L1 expression tumor proportion score (TPS) >= 1% in tumor cells, using the MERCK Food and Drug Administration (FDA) approved test as performed by local laboratories at the participating institutions.
- Patients must have measurable or non-measurable disease per the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Presence of malignant pleural fluid alone is allowed as study eligibility.
- Age >=18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
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- Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study.
- Absolute neutrophil count (ANC) >= 1500/mm^3 (within 14 days of randomization)
- Platelets >= 100,000/mm^3 (within 14 days of randomization)
- Prothrombin time (PT)/international normalized ratio (INR) =< 1.5 (within 14 days of randomization)
- Or if patient on therapeutic anticoagulation, PT/INR =< 3.0
- Partial thromboplastin time (PTT) =< institutional upper limit of normal (ULN) OR, if patient is on therapeutic anticoagulation, PTT must be =< 1.5 x ULN (within 14 days of randomization)
- Total Bilirubin =< 1.5 mg/dL (within 14 days of randomization)
- Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) < 5 X upper limit of normal (ULN) (within 14 days of randomization)
- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 5 X upper limit of normal ULN (within 14 days of randomization)
- Calculated creatinine clearance >= 45ml/min to be eligible to receive pemetrexed (within 14 days prior to randomization).
- Serum creatinine =< 1.5 X institutional upper limit of normal (ULN) serum creatinine (within 14 days prior to randomization)
Who cannot join
- Patients must NOT have received the following:
- Prior systemic chemotherapy or immunotherapy for advanced metastatic NSCLC. Patients treated with any prior checkpoint inhibitors for lung cancer are ineligible. Chemotherapy for non-metastatic disease (e.g. adjuvant therapy) is allowed if at least 6 months have elapsed since the prior chemotherapy and registration. Local therapy, e.g. palliative radiation, is allowed as long as a period of 14 days has passed since completion.
- Methotrexate (MTX) given in low doses for non-malignant conditions with last dose at least 14 days prior to date of registration will be allowed. Other low-dose chemotherapeutics for non-malignant conditions will be considered, but review by the study chair is required.
- Patient with known EGFR mutations (except exon 20 insertion), BRAF mutation (V600) or ALK or ROS1 translocations that can be treated with oral tyrosine kinase inhibitors are excluded.
- Patients with symptomatic brain metastases are excluded. Patients with treated or asymptomatic brain metastases are eligible if off steroids for at least 14 days. Anticonvulsants are allowed.
- Patients with active malignancy within the last 2 years are excluded (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 five years are eligible).
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- Patients must not have known pre-existing and clinically active interstitial lung disease.
- Patients must not have significant gastrointestinal disorders with diarrhea as a major symptom (e.g. Crohn's disease, malabsorption, etc.)
- Patients must not have history of auto-immune condition requiring ongoing or intermittent systemic treatment.
- Patients must not have history of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) classification of 3, unstable angina or poorly controlled arrhythmia, or myocardial infarction within 6 months.
- Patients must not have any other concomitant serious illness or organ system dysfunction that in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety of the study drug.
- Patients must not plan to receive any other investigational agents during the course of therapy.
- Women must not be pregnant or breast-feeding due to potential harm to the fetus or infant from cytotoxic chemotherapy and the unknown risk of pembrolizumab.
- All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy.
- A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria:1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
Trial locations and contacts
1 site in 1 country.
United States1 site
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
About this study
This study evaluates gut microbiome and functional status as modifiable biomarkers in predicting immunotherapy response and toxicity in patients with stage IV non-squamous non-small cell lung cancer receiving pembrolizumab alone or in combination with pemetrexed and carboplatin on the INSIGNIA trial. The goal of this study is to estimate the extent to which future interventions that seek to rationally modify the gut microbiome and/or functional status can improve outcomes.
Read the detailed description
PRIMARY OBJECTIVE:
- To quantify the performance of two modifiable biomarkers -- the microbiome and functional status - to use as predictive and/or prognostic indicators of clinical benefit (overall survival, progression-free survival) in lung cancer patients who receive randomized treatment combinations prescribed by the INSIGNA protocol.
SECONDARY OBJECTIVE:
- To quantify the predictive power of two modifiable biomarkers - the microbiome and functional status -- for the development of immune-related adverse events (irAEs).
OUTLINE:
Patients receive treatment by their treating physician as described in the INSIGNA protocol based on their designated treatment arm. Patients then undergo stool sample collection, complete questionnaires and functional status assessments, such as short physical performance battery over 10 minutes and 6 minute walk test, at baseline, days 40 (cycle 3), day 80 (cycle 5), day 180 (cycle 10) and end of treatment (up to 2 years).
- Conditions
- Lung Non-Squamous Non-Small Cell Carcinoma, Stage IIIB Lung Cancer AJCC v8, Stage IV Lung Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8, Stage IVB Lung Cancer AJCC v8
- Being tested
- Biospecimen Collection, Physical Performance Testing, Questionnaire Administration
- Medical subject headings
- Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Undergo stool sample
Physical Performance TestingOther
Also called Physical Fitness Testing, Physical Function Testing
Undergo short physical performance battery
Physical Performance TestingOther
Also called Physical Fitness Testing, Physical Function Testing
Perform 6-minute walk test
Questionnaire AdministrationOther
Complete questionnaires
| Study group | Role | What they receive |
|---|---|---|
| Ancillary-correlative (biospecimen, questionnaire, testing) | Patients receive treatment by their treating physician as described in the INSIGNA protocol based on their designated treatment arm. Patients then undergo stool sample collection, complete questionnaires and functional status assessments, such as short physical performance battery over 10 minutes and 6 minute walk test, at baseline, days 40 (cycle 3), day 80 (cycle 5), day 180 (cycle 10) and end of treatment (up to 2 years). Receives: Procedure: Biospecimen Collection; Other: Physical Performance Testing; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Performance of the microbiome as predictive indicator of clinical benefit (overall survival, progression free survival)
Count tables derived from the Kraken/Bracken pipeline output will be used to calculate the diversity metric Simpson's Index to quantify the number of species and evenness of the stool microbiome samples. Diversity will be binarized into high versus (vs) low at the median value, and then this variable used to stratify a Kaplan-Meier survival curve (predictive indicator). This will be further stratified by first-line treatment type (Arms A\&B vs Arm C) to evaluate microbe diversity predicts response by treatment (prognostic indicator).
Measured: Baseline up to 2 years
Performance of the microbiome as prognostic indicator of clinical benefit (overall survival, progression free survival)
The calculation will follow the methods described above but performed within treatment type (Arms A\&B separately from Arm C). The interpretation will rely on the comparison between treatments. For example, if a highly diverse microbiome is significantly predictive of overall survival in Arms A\&B but not within Arm C, then it would be a prognostic indicator of outcome in the context of treatment with ICIs. If it is predictive of response in both treatment groups then we will be unable to discern whether it is prognostic.
Measured: Baseline up to 2 years
Performance of functional status as predictive indicator of clinical benefit (progression free survival)
Functional status will be measured using a variety of methods including the 6 minute walk test (6MWT), for which they will be stratified by the median distance walked. This stratification will be used in a Kaplan-Meier survival curve to measure time to event, where the event is progression free survival.
Measured: Baseline up to 2 years
Performance of functional status as prognostic indicator of clinical benefit (progression free survival)
Physical activity will also be measured using a Short Physical Performance Battery (SPPB). Patients will be stratified by =< 7 and > 7 via grouping those assigned to the "very low physical function (0-3)" and "low physical function (4-6)" groups together, and the "moderate physical function (7-9)" and "high physical function (10-12)" groups together, assuming roughly equal split in the populations assigned by the stratification.
Measured: Baseline up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2021
- Study start18 May 2021
- Primary completion12 Oct 2022
- Study completion12 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung Non-Squamous Non-Small Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Ohio State University Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Daniel Spakowicz, Ohio State University Comprehensive Cancer Center
- Investigators
- Daniel Spakowicz, PhD, MS, Principal investigator, Ohio State University Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04954885
- Sponsor's protocol ID
- OSU-20187
- Other IDs
- NCI-2021-06339
- Status last verified
- Dec 2024
- First submitted
- 29 Jun 2021
- Last updated
- 27 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating Modifiable Biomarkers for the Prediction of Immunotherapy Response and Toxicity
- ClinicalTrials.gov ID
- NCT04954885
- Acronym / sponsor ID
- OSU-20187
- Conditions
- Lung Non-Squamous Non-Small Cell Carcinoma, Stage IIIB Lung Cancer AJCC v8, Stage IV Lung Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8, Stage IVB Lung Cancer AJCC v8
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Ohio State University Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- 18 May 2021 (actual)
- Primary completion
- 12 Oct 2022 (actual)
- Study completion
- 12 Oct 2022 (actual)
- First posted
- 8 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates gut microbiome and functional status as modifiable biomarkers in predicting immunotherapy response and toxicity in patients with stage IV non-squamous non-small cell lung cancer receiving pembrolizumab alone or in combination with pemetrexed and carboplatin on the INSIGNIA trial. The goal of this study is to estimate the extent to which future interventions that seek to rationally modify the gut microbiome and/or functional status can improve outcomes.
Detailed description
PRIMARY OBJECTIVE:
- To quantify the performance of two modifiable biomarkers -- the microbiome and functional status - to use as predictive and/or prognostic indicators of clinical benefit (overall survival, progression-free survival) in lung cancer patients who receive randomized treatment combinations prescribed by the INSIGNA protocol.
SECONDARY OBJECTIVE:
- To quantify the predictive power of two modifiable biomarkers - the microbiome and functional status -- for the development of immune-related adverse events (irAEs).
OUTLINE:
Patients receive treatment by their treating physician as described in the INSIGNA protocol based on their designated treatment arm. Patients then undergo stool sample collection, complete questionnaires and functional status assessments, such as short physical performance battery over 10 minutes and 6 minute walk test, at baseline, days 40 (cycle 3), day 80 (cycle 5), day 180 (cycle 10) and end of treatment (up to 2 years).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ancillary-correlative (biospecimen, questionnaire, testing) | – | Procedure: Biospecimen Collection, Other: Physical Performance Testing, Other: Questionnaire AdministrationPatients receive treatment by their treating physician as described in the INSIGNA protocol based on their designated treatment arm. Patients then undergo stool sample collection, complete questionnaires and functional status assessments, such as short physical performance battery over 10 minutes and 6 minute walk test, at baseline, days 40 (cycle 3), day 80 (cycle 5), day 180 (cycle 10) and end of treatment (up to 2 years). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Individuals who received randomized treatment from the INSIGNA protocol
Key inclusion criteria (17 listed)
- Histologically or cytologically confirmed stage IV non-squamous non-small cell lung cancer (NSCLC) (includes M1a, M1b stage disease, and American Joint Committee on Cancer (AJCC) 7th edition. Patients with T4NX disease (stage IIIB) with nodule in ipsilateral lung lobe are eligible if they are not candidates for combined chemotherapy and radiation.
- Formalin-fixed paraffin-embedded tumor tissue from a procedure performed within 6 months prior to registration is available for submission following registration. Formalin-fixed paraffin-embedded tumor tissue within six months of randomization available for analysis.
- PD-L1 expression tumor proportion score (TPS) >= 1% in tumor cells, using the MERCK Food and Drug Administration (FDA) approved test as performed by local laboratories at the participating institutions.
- Patients must have measurable or non-measurable disease per the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Presence of malignant pleural fluid alone is allowed as study eligibility.
- Age >=18 years.
Key exclusion criteria (15 listed)
- Patients must NOT have received the following:
- Methotrexate (MTX) given in low doses for non-malignant conditions with last dose at least 14 days prior to date of registration will be allowed. Other low-dose chemotherapeutics for non-malignant conditions will be considered, but review by the study chair is required.
- Patient with known EGFR mutations (except exon 20 insertion), BRAF mutation (V600) or ALK or ROS1 translocations that can be treated with oral tyrosine kinase inhibitors are excluded.
- Patients with symptomatic brain metastases are excluded. Patients with treated or asymptomatic brain metastases are eligible if off steroids for at least 14 days. Anticonvulsants are allowed.
- Patients with active malignancy within the last 2 years are excluded (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 five years are eligible).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Biospecimen CollectionUndergo stool sample | Procedure or surgery | Ancillary-correlative (biospecimen, questionnaire, testing) |
| Physical Performance TestingAlso: Physical Fitness Testing, Physical Function TestingUndergo short physical performance battery | Other | Ancillary-correlative (biospecimen, questionnaire, testing) |
| Physical Performance TestingAlso: Physical Fitness Testing, Physical Function TestingPerform 6-minute walk test | Other | Ancillary-correlative (biospecimen, questionnaire, testing) |
| Questionnaire AdministrationComplete questionnaires | Other | Ancillary-correlative (biospecimen, questionnaire, testing) |
Primary outcome
Performance of the microbiome as predictive indicator of clinical benefit (overall survival, progression free survival)
Time frame: Baseline up to 2 years
Count tables derived from the Kraken/Bracken pipeline output will be used to calculate the diversity metric Simpson's Index to quantify the number of species and evenness of the stool microbiome samples. Diversity will be binarized into high versus (vs) low at the median value, and then this variable used to stratify a Kaplan-Meier survival curve (predictive indicator). This will be further stratified by first-line treatment type (Arms A\&B vs Arm C) to evaluate microbe diversity predicts response by treatment (prognostic indicator).
Performance of the microbiome as prognostic indicator of clinical benefit (overall survival, progression free survival)
Time frame: Baseline up to 2 years
The calculation will follow the methods described above but performed within treatment type (Arms A\&B separately from Arm C). The interpretation will rely on the comparison between treatments. For example, if a highly diverse microbiome is significantly predictive of overall survival in Arms A\&B but not within Arm C, then it would be a prognostic indicator of outcome in the context of treatment with ICIs. If it is predictive of response in both treatment groups then we will be unable to discern whether it is prognostic.
Performance of functional status as predictive indicator of clinical benefit (progression free survival)
Time frame: Baseline up to 2 years
Functional status will be measured using a variety of methods including the 6 minute walk test (6MWT), for which they will be stratified by the median distance walked. This stratification will be used in a Kaplan-Meier survival curve to measure time to event, where the event is progression free survival.
Performance of functional status as prognostic indicator of clinical benefit (progression free survival)
Time frame: Baseline up to 2 years
Physical activity will also be measured using a Short Physical Performance Battery (SPPB). Patients will be stratified by =< 7 and > 7 via grouping those assigned to the "very low physical function (0-3)" and "low physical function (4-6)" groups together, and the "moderate physical function (7-9)" and "high physical function (10-12)" groups together, assuming roughly equal split in the populations assigned by the stratification.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2025.
- The JameslineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel Spakowicz, PhD, MS principal investigator
Ohio State University Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Lung Non-Squamous Non-Small Cell Carcinoma and Stage IIIB Lung Cancer AJCC v8, run by Ohio State University Comprehensive Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Performance of the microbiome as predictive indicator of clinical benefit (overall survival, progression free survival) (time frame: Baseline up to 2 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2025.