Stage IIIA Non-Small Cell Lung CancerPhase 1NCT02987998
Neoadjuvant Chemoradiation Plus Pembrolizumab Followed By Consolidation Pembrolizumab in NSCLC
A Phase 1 study testing Cisplatin, Etoposide and Pembrolizumab in people with Stage IIIA Non-Small Cell Lung Cancer, run by Nathan Pennell, MD, PhD at 1 site in United States.
Trial summary
The purpose of this study is to determine the feasibility and evaluate the safety of delivering chemoradiotherapy, the usual approach to non-small cell lung cancer, in combination with pembrolizumab (MK-3745), followed by consolidation pembrolizumab after surgical resection. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage IIIA Non-Small Cell Lung Cancer
- What is being tested?
- Cisplatin, Etoposide and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 19 May 2017to 28 Nov 2022
- Phase
- Phase 1
- 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
Who may be able to join
- Histologically confirmed stage 3A Non-Small Cell Lung Cancer
- Be willing and able to provide written informed consent/assent for the trial
- Have measurable or unmeasurable disease based on RECIST 1.1.
- Be willing to provide archival tissue from a tumor lesion or obtain a new biopsy if tissue unavailable.
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology group (ECOG) Performance Scale.
- Demonstrate adequate organ function
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- Absolute neutrophil count (ANC) ≥1,500/mcL
- Platelets ≥100,000 / mcL
- Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or erythropoiesis dependency
- Serum creatinine or Measured or calculated creatinine clearance ≤1.5 X upper limit of normal (ULN) or ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
- Serum total bilirubin ≤ 1.5 X ULN, or Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN
- Aspartate transaminase (AST) (SGOT) and Alanine transaminase (ALT) (SGPT) ≤ 2.5 X ULN or ≤ 5 X ULN for subjects with liver metastases
- Albumin ≥2.5 mg/dL
- International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
- Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
Who cannot join
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
- Has a known history of active Bacillus Tuberculosis (TB)
- Hypersensitivity to pembrolizumab or any of its excipients.
- Has had any prior chemotherapy, targeted small molecule therapy, or radiation therapy for the currently diagnosed cancer.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
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- 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.
- Has known history of, or any evidence of active, non-infectious pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, 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.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C
- Has received a live vaccine within 30 days of planned start of study therapy.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, 44195
About this study
Official title: A Phase I Safety and Feasibility Study of Neoadjuvant Chemoradiation Plus Pembrolizumab Followed By Consolidation Pembrolizumab in Resectable Stage 3A Non-Small Cell Lung Cancer
The purpose of this study is to determine the feasibility and evaluate the safety of delivering chemoradiotherapy, the usual approach to non-small cell lung cancer, in combination with pembrolizumab (MK-3745), followed by consolidation pembrolizumab after surgical resection. Consolidation therapy is treatment given following the initial treatment.
Pembrolizumab is an investigational drug (also known as Keytruda), which has been approved by the FDA for use in certain types of skin cancer (melanoma), and for use in certain types of head and neck cancer. However, it has not been approved for use in other cancers such as non-small cell lung cancer (NSCLC). Pembrolizumab is a monoclonal antibody that binds to the surface of some cells of the immune system and activates them against cancer cells. It is not chemotherapy.
Read the detailed description
The primary hypothesis is that the addition of pembrolizumab to neoadjuvant concurrent chemoradiation, followed by consolidation pembrolizumab, will be safe and feasible to deliver to patients with resectable stage 3A Non-small cell lung cancer (NSCLC).
This study also plans to observe the efficacy of this combination in the overall and biomarker-positive population.
Primary Objective Primary objective of this phase 1 study is to determine safety and feasibility of MK3475 with standard of care therapy of chemotherapy with radiation for newly diagnosed stage 3 lung carcinoma.
- To define the Safety, tolerability and feasibility of MK3475 in combination with chemotherapy with cisplatin and etoposide along with 45 Gy of radiation in newly diagnosed stage 3 non-small cell lung carcinoma.
Secondary Objective(s)
- Progression Free Survival
- Objective response rate,
- Complete pathologic response rate,
- Nodal downstaging at surgery,
- Overall survival,
- Safety and tolerability
Correlative Objective(s) Exploratory objectives: Overall response rate, progression free survival, overall survival in Programmed death-ligand (PDL-1) positive versus negative subgroups
Study Design This is an open-label, single arm phase I trial of neoadjuvant chemotherapy + pembrolizumab with concurrent radiation followed by surgical resection and consolidation pembrolizumab in resectable stage 3A (N2+) NSCLC.
Eligible patients will have biopsy-confirmed T1-3N2M0 (stage IIIA) non-small cell lung cancer (adenocarcinoma, squamous cell carcinoma, or large cell/NSCLC not otherwise specified), performance status 0-1, adequate lung function and deemed medically resectable by a thoracic surgeon, adequate organ function for chemotherapy, and no contraindications to pembrolizumab (i.e. autoimmune disorders or underlying pulmonary fibrosis).
Because pembrolizumab has been safely added to multiple platinum doublet chemotherapy regimens in lung cancer but not yet tested in the setting of concurrent radiation, we plan to evaluate safety and feasibility of the combination therapy. 10 patients will be enrolled at the full starting dose of all 3 agents. If 3 or more (>30%) have grade 3 or higher pulmonary toxicity or any grade 4 nonhematologic toxicity, the study will be stopped. If 2 or fewer have > grade 3 pulmonary toxicity or > grade 4 other nonhematologic toxicity, then an additional 10 will be enrolled. If 5 or fewer (<25%) of the 20 patients have > grade 3 pulmonary toxicity or > grade 4 other nonhematologic toxicity, then this regimen will be deemed safe and feasible for further study.
- Conditions
- Stage IIIA Non-Small Cell Lung Cancer
- Being tested
- Cisplatin, Etoposide, Pembrolizumab, Radiation
- Keywords
- Pembrolizumab, Chemoradiation
- 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.
CisplatinDrug
Cisplatin (50mg/m2 IV D1, 8, 29, 36)
EtoposideDrug
Etoposide (50mg/m2 IV D1-5, 29-33)
PembrolizumabDrug
Pembrolizumab (200mg IV D1, 21, 42)
RadiationDrug
Radiation (1.8Gy/D to 45Gy in 25 fractions)
| Study group | Role | What they receive |
|---|---|---|
| Resectable Patients | Experimental | Chemoradiation (Cisplatin + Etoposide + Pembrolizumab with concurrent radiation). Patients will be assessed for surgery followed by consolidation therapy Receives: Drug: Cisplatin; Drug: Etoposide; Drug: Pembrolizumab; Drug: Radiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with grade 3 pulmonary toxicity or grade 4 other non hematologic toxicity
If 5 or fewer (<25%) of the 20 patients have > grade 3 pulmonary toxicity or > grade 4 other nonhematologic toxicity, then this regimen will be deemed safe and feasible for further study
Measured: Up to 5 years
Secondary outcomes (5)
Progression Free Survival
Time from beginning of treatment to progression, death, or five years, whichever came first. Progression is defined as Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm
Measured: Up to 5 years
Objective Response Rate
Number of patients with objective response (CR + PR) where complete response is defined as Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. And Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Measured: Up to 5 years
Complete Pathologic Response Rate
Pathological complete response is defined as absence of foci of tumor cells at the local site (pCR)
Measured: Up to 5 years
Nodal Downstaging at Surgery
Number of patients with reduced stages in nodes at surgery
Measured: Up to 4 weeks after induction treatment
Overall Survival
Time from beginning of treatment to death or 5 year, whichever comes first
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2016 (estimated)
- Study start19 May 2017
- Primary completion28 Nov 2022
- Study completion28 Nov 2022
Why it stopped: higher than expected rate of toxicity \& unrealistic timeline to complete trial under company's proposed plan to reopen
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stage IIIA 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nathan Pennell, MD, PhD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Nathan Pennell, MD, PhD, Case Comprehensive Cancer Center
- Investigators
- Nathan Pennell, MD, PhD, Principal investigator, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02987998
- Sponsor's protocol ID
- CASE4516
- Status last verified
- Dec 2022
- First submitted
- 7 Dec 2016
- Last updated
- 19 Dec 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Safety and Feasibility Study of Neoadjuvant Chemoradiation Plus Pembrolizumab Followed By Consolidation Pembrolizumab in Resectable Stage 3A Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT02987998
- Acronym / sponsor ID
- CASE4516
- Conditions
- Stage IIIA Non-Small Cell Lung Cancer
- Keywords
- Pembrolizumab, Chemoradiation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: higher than expected rate of toxicity \& unrealistic timeline to complete trial under company's proposed plan to reopen
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Nathan Pennell, MD, PhDUniversity, hospital or other
- Study start
- 19 May 2017 (actual)
- Primary completion
- 28 Nov 2022 (actual)
- Study completion
- 28 Nov 2022 (actual)
- First posted
- 9 Dec 2016 (estimated)
- 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.
The purpose of this study is to determine the feasibility and evaluate the safety of delivering chemoradiotherapy, the usual approach to non-small cell lung cancer, in combination with pembrolizumab (MK-3745), followed by consolidation pembrolizumab after surgical resection. Consolidation therapy is treatment given following the initial treatment.
Pembrolizumab is an investigational drug (also known as Keytruda), which has been approved by the FDA for use in certain types of skin cancer (melanoma), and for use in certain types of head and neck cancer. However, it has not been approved for use in other cancers such as non-small cell lung cancer (NSCLC). Pembrolizumab is a monoclonal antibody that binds to the surface of some cells of the immune system and activates them against cancer cells. It is not chemotherapy.
Detailed description
The primary hypothesis is that the addition of pembrolizumab to neoadjuvant concurrent chemoradiation, followed by consolidation pembrolizumab, will be safe and feasible to deliver to patients with resectable stage 3A Non-small cell lung cancer (NSCLC).
This study also plans to observe the efficacy of this combination in the overall and biomarker-positive population.
Primary Objective Primary objective of this phase 1 study is to determine safety and feasibility of MK3475 with standard of care therapy of chemotherapy with radiation for newly diagnosed stage 3 lung carcinoma.
- To define the Safety, tolerability and feasibility of MK3475 in combination with chemotherapy with cisplatin and etoposide along with 45 Gy of radiation in newly diagnosed stage 3 non-small cell lung carcinoma.
Secondary Objective(s)
- Progression Free Survival
- Objective response rate,
- Complete pathologic response rate,
- Nodal downstaging at surgery,
- Overall survival,
- Safety and tolerability
Correlative Objective(s) Exploratory objectives: Overall response rate, progression free survival, overall survival in Programmed death-ligand (PDL-1) positive versus negative subgroups
Study Design This is an open-label, single arm phase I trial of neoadjuvant chemotherapy + pembrolizumab with concurrent radiation followed by surgical resection and consolidation pembrolizumab in resectable stage 3A (N2+) NSCLC.
Eligible patients will have biopsy-confirmed T1-3N2M0 (stage IIIA) non-small cell lung cancer (adenocarcinoma, squamous cell carcinoma, or large cell/NSCLC not otherwise specified), performance status 0-1, adequate lung function and deemed medically resectable by a thoracic surgeon, adequate organ function for chemotherapy, and no contraindications to pembrolizumab (i.e. autoimmune disorders or underlying pulmonary fibrosis).
Because pembrolizumab has been safely added to multiple platinum doublet chemotherapy regimens in lung cancer but not yet tested in the setting of concurrent radiation, we plan to evaluate safety and feasibility of the combination therapy. 10 patients will be enrolled at the full starting dose of all 3 agents. If 3 or more (>30%) have grade 3 or higher pulmonary toxicity or any grade 4 nonhematologic toxicity, the study will be stopped. If 2 or fewer have > grade 3 pulmonary toxicity or > grade 4 other nonhematologic toxicity, then an additional 10 will be enrolled. If 5 or fewer (<25%) of the 20 patients have > grade 3 pulmonary toxicity or > grade 4 other nonhematologic toxicity, then this regimen will be deemed safe and feasible for further study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Resectable Patients | Experimental | Drug: Cisplatin, Drug: Etoposide, Drug: Pembrolizumab, Drug: RadiationChemoradiation (Cisplatin + Etoposide + Pembrolizumab with concurrent radiation). Patients will be assessed for surgery followed by consolidation therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Histologically confirmed stage 3A Non-Small Cell Lung Cancer
- Be willing and able to provide written informed consent/assent for the trial
- Have measurable or unmeasurable disease based on RECIST 1.1.
- Be willing to provide archival tissue from a tumor lesion or obtain a new biopsy if tissue unavailable.
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology group (ECOG) Performance Scale.
Key exclusion criteria (16 listed)
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
- Has a known history of active Bacillus Tuberculosis (TB)
- Hypersensitivity to pembrolizumab or any of its excipients.
- Has had any prior chemotherapy, targeted small molecule therapy, or radiation therapy for the currently diagnosed cancer.
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 |
|---|---|---|
| CisplatinCisplatin (50mg/m2 IV D1, 8, 29, 36) | Drug | Resectable Patients |
| EtoposideEtoposide (50mg/m2 IV D1-5, 29-33) | Drug | Resectable Patients |
| PembrolizumabPembrolizumab (200mg IV D1, 21, 42) | Drug | Resectable Patients |
| RadiationRadiation (1.8Gy/D to 45Gy in 25 fractions) | Drug | Resectable Patients |
Primary outcome
Number of patients with grade 3 pulmonary toxicity or grade 4 other non hematologic toxicity
Time frame: Up to 5 years
If 5 or fewer (<25%) of the 20 patients have > grade 3 pulmonary toxicity or > grade 4 other nonhematologic toxicity, then this regimen will be deemed safe and feasible for further study
5 secondary outcomes
Progression Free Survival
Time frame: Up to 5 years
Objective Response Rate
Time frame: Up to 5 years
Complete Pathologic Response Rate
Time frame: Up to 5 years
Nodal Downstaging at Surgery
Time frame: Up to 4 weeks after induction treatment
Overall Survival
Time frame: Up to 5 years
Results and safety
The study was stopped early (reason given: higher than expected rate of toxicity \& unrealistic timeline to complete trial under company's proposed plan to reopen). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2022.
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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.
Nathan Pennell, MD, PhD principal investigator
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cisplatin, Etoposide and Pembrolizumab in people with Stage IIIA Non-Small Cell Lung Cancer, run by Nathan Pennell, MD, PhD 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 16 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: stopped early, as of the sponsor's last update on 19 Dec 2022. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 stopped early (reason given: higher than expected rate of toxicity \& unrealistic timeline to complete trial under company's proposed plan to reopen). Results are not available in the source record.
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?
Number of patients with grade 3 pulmonary toxicity or grade 4 other non hematologic toxicity (time frame: Up to 5 years). 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 19 Dec 2022.