Non Small Cell Lung CancerPhase 2HFHS 21-01NCT04754815
Study of Pembrolizumab With Single Agent Chemotherapy in Elderly Patients With Advanced NSCLC
A Phase 2 study testing Pembrolizumab, Pemetrexed and Paclitaxel in people with Non Small Cell Lung Cancer and Advanced Lung Non-Small Cell Carcinoma, run by Shirish Gadgeel.
Trial summary
This Phase II trial is to see how well single agent chemotherapy and pembrolizumab work elderly patients (≥ 75 years) with advanced non small cell lung cancer (NSCLC). Pembrolizumab stimulates your immune system to help fight lung cancer. This treatment approach may be better tolerated in elderly patients. Read more about this study
- Who is it for?
- Ages 75 to 90 years
- Conditions the study is for
- Non Small Cell Lung Cancer, Advanced Lung Non-Small Cell Carcinoma, PD-L1 Gene Mutation
- What is being tested?
- Pembrolizumab, Pemetrexed and Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Apr 2021to 1 Apr 2026
- Phase
- Phase 2
- 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 75 to 90 years
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Male/female participants who are ≥75 years of age on the day of signing informed consent with histologically confirmed diagnosis of stage IV (AJCC version 8) NSCLC with tumor PD-L1 < 50% and negative 'driver' alterations in EGFR, ALK and ROS1 will be enrolled in this study. Tumor PD-L1 expression should be assessed by FDA approved Dako 22C3 test.
- Patients should be treatment naïve for stage IV NSCLC. Patients previously treated for earlier stages of lung cancer are eligible if they have not received systemic therapy for a minimum of 180 days prior to the start of study therapy.
- The participant provides written informed consent for the trial.
- Have measurable disease based on RECIST 1.1 or evaluable disease.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0,1. Evaluation of ECOG is to be performed within 7 days prior to the date of start of therapy.
- Male participants:
- A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 180 days after the last dose of study treatment and refrain from donating sperm during this period.
- Have adequate organ function as evidenced by laboratory assessment. Specimens must be collected within 10 days prior to the start of study treatment.
Who cannot join
- Patient could not have received any anti-cancer systemic therapy for a minimum of 180 days prior to the start of study therapy. Patient should not have received prior PD-1 or PD-L1 therapy.
- Has received prior definitive palliative radiotherapy within 2 weeks or definitive radiotherapy within 6 months of study intervention. Participants must have recovered from all radiation-related toxicities, require corticosteroids no more than 10 mg of prednisone or equivalent dose of other steroids, and not have had clinical radiation pneumonitis.
- Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
- Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. Patients with cancers such as PSA only prostate cancer may be considered after discussion with the principal investigator.
Show all 18Show fewer
- Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other in-situ cancers
- Has symptomatic CNS metastases and/or carcinomatous meningitis. Subjects with asymptomatic brain metastases may participate provided they are clinically stable and are not using steroids equivalent to >10mg of prednisone day prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of whether it is symptomatic or not.
- Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: No HIV testing is required unless mandated by local health authority.
- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
- Has a known history of active TB (Bacillus Tuberculosis).
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Has had an allogenic tissue/solid organ transplant.
About this study
Official title: Phase II Study of Pemetrexed or Nab-paclitaxel With Pembrolizumab in Elderly (>/= 75 Years) Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)
This Phase II trial is to see how well single agent chemotherapy and pembrolizumab work elderly patients (≥ 75 years) with advanced non small cell lung cancer (NSCLC). Pembrolizumab stimulates your immune system to help fight lung cancer. This treatment approach may be better tolerated in elderly patients.
Read the detailed description
Primary Objective(s), Hypothesis(es), and Endpoint(s)
- Objective: To evaluate the efficacy of single agent chemotherapy and pembrolizumab in elderly (≥ 75 years) advanced NSCLC patients Hypothesis: We propose that single agent chemotherapy with pembrolizumab will be better tolerated and will provide similar efficacy as platinum-based combination chemotherapy with pembrolizumab in advanced elderly (≥75 years) NSCLC patients.
Primary Endpoint:
- Assess median PFS in elderly (≥ 75 years) advanced NSCLC patients with tumor PD-L1 (<50%) treated with pemetrexed or nab-paclitaxel and pembrolizumab.
Secondary Objective(s), Hypothesis(es), and Endpoint(s)
- Objective: To assess additional measure of efficacy of the regimen. To define the toxicity of the regimen in addition
II. Hypothesis: In this patient population single agent chemotherapy and pembrolizumab will provide similar efficacy but improved tolerability as 2 drug combination with pembrolizumab.
Secondary Endpoints:
- Assess overall survival in the study population II. Assess the toxicities with the study therapy and the rate of discontinuation of study therapy due to toxicities related to study therapy
Exploratory Objective:
- Objective: To define correlatives that can identify patients most likely to benefit from the study therapy.
II. Correlate PFS with blood-based tumor mutational burden and ctDNA.
Participants who experience confirmed disease progression or start a new anticancer therapy, will move into the Survival Follow-Up Phase and should be contacted by telephone every 12 weeks to assess for survival status until death, withdrawal of consent, or the end of the trial, whichever occurs first.
- Being tested
- Pembrolizumab, Pemetrexed, Paclitaxel, Nab-paclitaxel, Laboratory Biomarker Analysis
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called Keytruda
PD-L1 inhibitor administered as an intravenous (IV) infusion.
PemetrexedDrug
Also called ALIMTA
Folate analog metabolic inhibitor administered as an intravenous (IV) infusion single agent chemotherapy for advanced NSCLC
PaclitaxelDrug
Also called TAXOL
A novel antimicrotubular agent administered as an intravenous (IV) infusion single agent chemotherapy for advanced NSCLC
Nab-paclitaxelDrug
Also called ABRAXANE®
Microtubule inhibitor administered as an intravenous (IV) infusion indicated for the treatment of locally advanced or metastatic NSCLC
Laboratory Biomarker AnalysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab + Pemetrexed | Experimental | Pembrolizumab 200mg intravenous (IV) infusion on Day 1 of each 21 day cycle. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity + pemetrexed 500mg intravenous (IV) infusion (with vitamin supplementation) on Day 1 of each 21 day cycle up to 35 cycles or until disease progression. Receives: Drug: Pembrolizumab; Drug: Pemetrexed; Other: Laboratory Biomarker Analysis |
| Pembrolizumab + Paclitaxel OR Paclitaxel | Experimental | Pembrolizumab 200mg intravenous (IV) infusion on Day 1 of each 21 day cycle. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity
+ Paclitaxel 100 mg/m2 intravenous (IV) infusion on days 1 and 8 of each 21 day treatment cycle
OR Paclitaxel100 mg/m2 intravenous (IV) infusion on days 1 and 8 of each 21 day treatment cycle until disease progression. Receives: Drug: Pembrolizumab; Drug: Paclitaxel; Drug: Nab-paclitaxel; Other: Laboratory Biomarker Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Median progression free survival
Length of time treatment to disease progression
Measured: 6 months
Secondary outcomes (1)
Overall survival
Time from progression until death
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2021
- Study start1 Apr 2021 (estimated)
- Primary completion1 Apr 2025 (estimated)
- Study completion1 Apr 2026 (estimated)
Why it stopped: Logistical challenges primarily due to COVID led to delay in starting the study and now is not felt to be clinically relevant.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Single arm open label with 2 treatment options
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shirish Gadgeel
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor-investigator, Shirish Gadgeel, Henry Ford Health System
- Investigators
- Shirish Gadgeel, MBBS, Principal investigator, Henry Ford Health System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04754815
- Sponsor's protocol ID
- HFHS 21-01
- Acronym
- HFHS 21-01
- Status last verified
- Feb 2021
- First submitted
- 10 Feb 2021
- Last updated
- 29 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: The individual participant data (IPD) will be shared with Dr. Muneesh Tewari's laboratory at University of Michigan for the CtDNA samples. Outside, of this IPD will be shared with Merck who is providing drug for this protocol. IPD will not be shared with any researchers outside of this. All subjects are assigned a study specific ID number. No direct patient identifiers leave the site.
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Pemetrexed or Nab-paclitaxel With Pembrolizumab in Elderly (>/= 75 Years) Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)
- ClinicalTrials.gov ID
- NCT04754815
- Acronym / sponsor ID
- HFHS 21-01 / HFHS 21-01
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Logistical challenges primarily due to COVID led to delay in starting the study and now is not felt to be clinically relevant.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Shirish GadgeelUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 1 Apr 2021 (estimated)
- Primary completion
- 1 Apr 2025 (estimated)
- Study completion
- 1 Apr 2026 (estimated)
- First posted
- 15 Feb 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 Phase II trial is to see how well single agent chemotherapy and pembrolizumab work elderly patients (≥ 75 years) with advanced non small cell lung cancer (NSCLC). Pembrolizumab stimulates your immune system to help fight lung cancer. This treatment approach may be better tolerated in elderly patients.
Detailed description
Primary Objective(s), Hypothesis(es), and Endpoint(s)
- Objective: To evaluate the efficacy of single agent chemotherapy and pembrolizumab in elderly (≥ 75 years) advanced NSCLC patients Hypothesis: We propose that single agent chemotherapy with pembrolizumab will be better tolerated and will provide similar efficacy as platinum-based combination chemotherapy with pembrolizumab in advanced elderly (≥75 years) NSCLC patients.
Primary Endpoint:
- Assess median PFS in elderly (≥ 75 years) advanced NSCLC patients with tumor PD-L1 (<50%) treated with pemetrexed or nab-paclitaxel and pembrolizumab.
Secondary Objective(s), Hypothesis(es), and Endpoint(s)
- Objective: To assess additional measure of efficacy of the regimen. To define the toxicity of the regimen in addition
II. Hypothesis: In this patient population single agent chemotherapy and pembrolizumab will provide similar efficacy but improved tolerability as 2 drug combination with pembrolizumab.
Secondary Endpoints:
- Assess overall survival in the study population II. Assess the toxicities with the study therapy and the rate of discontinuation of study therapy due to toxicities related to study therapy
Exploratory Objective:
- Objective: To define correlatives that can identify patients most likely to benefit from the study therapy.
II. Correlate PFS with blood-based tumor mutational burden and ctDNA.
Participants who experience confirmed disease progression or start a new anticancer therapy, will move into the Survival Follow-Up Phase and should be contacted by telephone every 12 weeks to assess for survival status until death, withdrawal of consent, or the end of the trial, whichever occurs first.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Single arm open label with 2 treatment options
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab + Pemetrexed | Experimental | Drug: Pembrolizumab, Drug: Pemetrexed, Other: Laboratory Biomarker AnalysisPembrolizumab 200mg intravenous (IV) infusion on Day 1 of each 21 day cycle. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity + pemetrexed 500mg intravenous (IV) infusion (with vitamin supplementation) on Day 1 of each 21 day cycle up to 35 cycles or until disease progression. |
| Pembrolizumab + Paclitaxel OR Paclitaxel | Experimental | Drug: Pembrolizumab, Drug: Paclitaxel, Drug: Nab-paclitaxel, Other: Laboratory Biomarker AnalysisPembrolizumab 200mg intravenous (IV) infusion on Day 1 of each 21 day cycle. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity + Paclitaxel 100 mg/m2 intravenous (IV) infusion on days 1 and 8 of each 21 day treatment cycle OR Paclitaxel100 mg/m2 intravenous (IV) infusion on days 1 and 8 of each 21 day treatment cycle until disease progression. |
Who may qualify
- Ages
- 75 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (8 listed)
- Male/female participants who are ≥75 years of age on the day of signing informed consent with histologically confirmed diagnosis of stage IV (AJCC version 8) NSCLC with tumor PD-L1 < 50% and negative 'driver' alterations in EGFR, ALK and ROS1 will be enrolled in this study. Tumor PD-L1 expression should be assessed by FDA approved Dako 22C3 test.
- Patients should be treatment naïve for stage IV NSCLC. Patients previously treated for earlier stages of lung cancer are eligible if they have not received systemic therapy for a minimum of 180 days prior to the start of study therapy.
- The participant provides written informed consent for the trial.
- Have measurable disease based on RECIST 1.1 or evaluable disease.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0,1. Evaluation of ECOG is to be performed within 7 days prior to the date of start of therapy.
Key exclusion criteria (18 listed)
- Patient could not have received any anti-cancer systemic therapy for a minimum of 180 days prior to the start of study therapy. Patient should not have received prior PD-1 or PD-L1 therapy.
- Has received prior definitive palliative radiotherapy within 2 weeks or definitive radiotherapy within 6 months of study intervention. Participants must have recovered from all radiation-related toxicities, require corticosteroids no more than 10 mg of prednisone or equivalent dose of other steroids, and not have had clinical radiation pneumonitis.
- Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
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 |
|---|---|---|
| PembrolizumabAlso: KeytrudaPD-L1 inhibitor administered as an intravenous (IV) infusion. | Drug | Pembrolizumab + Paclitaxel OR Paclitaxel, Pembrolizumab + Pemetrexed |
| PemetrexedAlso: ALIMTAFolate analog metabolic inhibitor administered as an intravenous (IV) infusion single agent chemotherapy for advanced NSCLC | Drug | Pembrolizumab + Pemetrexed |
| PaclitaxelAlso: TAXOLA novel antimicrotubular agent administered as an intravenous (IV) infusion single agent chemotherapy for advanced NSCLC | Drug | Pembrolizumab + Paclitaxel OR Paclitaxel |
| Nab-paclitaxelAlso: ABRAXANE®Microtubule inhibitor administered as an intravenous (IV) infusion indicated for the treatment of locally advanced or metastatic NSCLC | Drug | Pembrolizumab + Paclitaxel OR Paclitaxel |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Pembrolizumab + Paclitaxel OR Paclitaxel, Pembrolizumab + Pemetrexed |
Primary outcome
Median progression free survival
Time frame: 6 months
Length of time treatment to disease progression
1 secondary outcome
Overall survival
Time frame: 12 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2022.
- Individual participant dataSharing planned: No. The individual participant data (IPD) will be shared with Dr. Muneesh Tewari's laboratory at University of Michigan for the CtDNA samples. Outside, of this IPD will be shared with Merck who is providing drug for this protocol. IPD will not be shared with any researchers outside of this. All subjects are assigned a study specific ID number. No direct patient identifiers leave the site.
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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.
Shirish Gadgeel, MBBS principal investigator
Henry Ford Health System
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab, Pemetrexed and Paclitaxel in people with Non Small Cell Lung Cancer and Advanced Lung Non-Small Cell Carcinoma, run by Shirish Gadgeel.
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 8 inclusion and 18 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: withdrawn, as of the sponsor's last update on 29 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Median progression free survival (time frame: 6 months). 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 29 Mar 2022.