Non Small Cell Lung Cancer Stage IIIBPhase 2NCT03302247
Depletion of Myeloid Derived Suppressor Cells to Enhance Anti PD-1 Therapy
A Phase 2 study testing Nivolumab and Nivolumab+Gemcitabine in people with Non Small Cell Lung Cancer Stage IIIB, run by Fox Chase Cancer Center at 1 site in United States.
Trial summary
Metastatic non small cell lung cancer can be treated with cytotoxic chemotherapy or using recently approved immunotherapy with antibody, Nivolumab. Both the therapies have limitation due to development of tolerance or immunosuppression. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer Stage IIIB
- What is being tested?
- Nivolumab and Nivolumab+Gemcitabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jan 2018to 12 Jul 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 diagnosis of non-small cell lung cancer (NSCLC). Patients should have stage IV disease (AJCC 7th edition), stage IIIb disease that is not amenable to potentially curative treatment (e.g. chemoradiotherapy) or unequivocal progression in a prior irradiated field. Measurable or evaluable disease is required.
- Fresh/ archived tumor tissue available for molecular marker testing is required for entry. A tumor block or at least 5 unstained slides must be available. As an alternative FFPE cell block that is sufficient for histologic analysis is acceptable. If a patient has had PD-L1 status previously determined with and FDA approved assay, they have met this requirement. Tissue is still requested (but not required) for further analysis
- Age > 18 years.
- ECOG performance status 0 or 1
- Patients must have normal organ and marrow functions as defined below:
- White blood cells (WBC) >2,000/mcL; Platelets >100,000/mcL; Hb ≥9g/dl; Absolute neutrophil count (ANC) >1,500/mcL; Serum creatinine ≤1.5 x ULN, or
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- Creatinine clearance (CrCl) ≥50 ml/min (if using Cockcroft Gault formula below):
- Female CrCl= ((140 - age in years)/(72 x serum creatinine in mg/dL)) x weight in kg x 0.85; Male CrCl= ((140 - age in years)/(72 x serum creatinine in mg/dL) x weight in kg x 1.0; AST/SGOT ≤ 3 x ULN
- Total bilirubin:
- If no known liver metastasis: total bilirubin ≤ 1.5 x institutional upper limit (ULN) (except, subjects with Gilbert Syndrome who may have total bilirubin < 3.0 mg/dl; If known metastasis: total bilirubin ≤ 5 ULN
- Negative serum pregnancy test result in Women os Child -bearing Potential (WOCBP)
- Prior therapies:
- Patients without activating mutations and gene rearrangements should have received at least one prior chemotherapy regimen. Any number of prior therapies is allowed except for immunotherapy (e.g. anti PD-1, PD-L1, vaccines, CTLA-4 etc.),
- Patients with activating mutations with known documented benefit from tyrosine kinase inhibitors should have received and demonstrated progression with that inhibitor (e.g. EGFR del 19 mutation should have been treated with gefitinib, erlotinib or afatanib etc). ALK rearrangements should have been treated with an ALK inhibitor. Patients who have progressed on these agents should be assessed, if appropriate, for resistance mutations susceptible to approved agents and treated with that agent.
- No prior gemcitabine treatment
- Ability to understand and willingness to sign a written informed consent and HIPAA consent document
Who cannot join
- Patients with active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
- Patients requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Subjects are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if > 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
- As there is a potential for hepatic toxicity with nivolumab, drugs with predisposition to hepatotoxicity should be used with caution in patients treated with nivolumab-containing regimen.
- Patients are excluded if they have active brain metastases or leptomeningeal metastases. Subjects with brain metastases are eligible if metastases have been treated without clinical or radiologic evidence of progression for 14 days prior to initiation of treatment. An MRI within 14 days of commencing therapy is required for patients with a history of brain metastases.
- There must be no requirement for immunosuppressive doses of systemic corticosteroids (>10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab.
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- Uncontrolled inter-current illness that would increase the risk of toxicity or limit compliance with study requirements. This includes but is not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness or social situations that would limit compliance with study requirements.
- Known HIV-positive patients on combination antiretroviral therapy are ineligible because of the abnormal immune response that results from HIV disease.
- Patients should be excluded if they are positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
- Patients who have had systemic (IV) cytotoxic chemotherapy or any other investigational agents within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. If a patient received an oral agent, treatment on study can not commence at least five half-lives of the agent have elapsed.
- Subjects with previous malignancies (except non-melanoma skin cancers, and in situ cancers such as the following: bladder, gastric, colon, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry and no additional therapy is required or anticipated to be required during the study period.
- Other active malignancy requiring concurrent intervention.
- Subjects with any history of interstitial lung disease.
- Pregnant or breast feeding.
Trial locations and contacts
1 site in 1 country.
United States1 site
Fox Chase Cancer Center - Philadelphia
Philadelphia, Pennsylvania, 19111-2497
About this study
Metastatic non small cell lung cancer can be treated with cytotoxic chemotherapy or using recently approved immunotherapy with antibody, Nivolumab. Both the therapies have limitation due to development of tolerance or immunosuppression. This trial combines one drug from each category, immunotherapeutic Nivolumab and chemotherapeutic gemcitabine as it was reported that gemcitabine reduces immunosuppression by killing myeloid derived suppressor cells, thereby increasing the efficacy of Nivolumab.
Read the detailed description
Primary Objective
- The primary objective of this proposal is to evaluate gemcitabine as a method of MDSC depletion.
Secondary Objectives
- Evaluate whether these measures result in enhanced T-cell activity and/or NK cell function and number.
- Determine the tolerability and clinical activity (including response rate and survival) of this approach.
- Correlate MDSC number with tumor PD-L1 expression
- Conditions
- Non Small Cell Lung Cancer Stage IIIB
- Being tested
- Nivolumab, Nivolumab+Gemcitabine
- 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.
NivolumabBiological
Monoclonal antibody against non small cell lung cancer
Nivolumab+GemcitabineDrug
Gemcitabine is added to the Nivolumab treatment
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab+Gemcitabine | Experimental | Nivolumab infusion on day 1 and 15 with the addition of gencitabine on day 1, 8 and 15 of 28 day cycle Receives: Biological: Nivolumab; Drug: Nivolumab+Gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Decrease in Macrophage Derived Suppressor Cells (MDSC) Numbers as a Result of Treatment With Gemcitabine.
Immunosuppression in terms of number of circulating MDSC in the blood by comparing within each arm reduction in the number of MDSCs after each cycle of treatment
Measured: 2 years
Secondary outcomes (1)
Increase in T-cell Activity
Evaluate if MDSC elimination by gemcitabine results in increase in T-cell activity
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2017
- Study start15 Jan 2018
- Primary completion21 Mar 2019
- Study completion12 Jul 2019
Why it stopped: Unable to accrue subjects
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non Small Cell Lung Cancer Stage IIIBStudies of the same condition, open and under way.
- More trials run by Fox Chase 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Nivolumab 240mg, IV on day 1, 15 + Gemcitabine 1000mg/m2, IV on day 1, 8, 15 of 28 days cycle
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fox Chase Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03302247
- Sponsor's protocol ID
- TH-113
- Status last verified
- Oct 2020
- First submitted
- 27 Sep 2017
- Last updated
- 28 Oct 2020
- Results posted
- Yes, on ClinicalTrials.gov
- 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 28 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Depletion of Myeloid Derived Suppressor Cells to Enhance Anti PD-1 Therapy
- ClinicalTrials.gov ID
- NCT03302247
- Acronym / sponsor ID
- TH-113
- Conditions
- Non Small Cell Lung Cancer Stage IIIB
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Unable to accrue subjects
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Fox Chase Cancer CenterUniversity, hospital or other
- Study start
- 15 Jan 2018 (actual)
- Primary completion
- 21 Mar 2019 (actual)
- Study completion
- 12 Jul 2019 (actual)
- First posted
- 5 Oct 2017 (actual)
- Results
- Posted 28 Oct 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Metastatic non small cell lung cancer can be treated with cytotoxic chemotherapy or using recently approved immunotherapy with antibody, Nivolumab. Both the therapies have limitation due to development of tolerance or immunosuppression. This trial combines one drug from each category, immunotherapeutic Nivolumab and chemotherapeutic gemcitabine as it was reported that gemcitabine reduces immunosuppression by killing myeloid derived suppressor cells, thereby increasing the efficacy of Nivolumab.
Detailed description
Primary Objective
- The primary objective of this proposal is to evaluate gemcitabine as a method of MDSC depletion.
Secondary Objectives
- Evaluate whether these measures result in enhanced T-cell activity and/or NK cell function and number.
- Determine the tolerability and clinical activity (including response rate and survival) of this approach.
- Correlate MDSC number with tumor PD-L1 expression
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Nivolumab 240mg, IV on day 1, 15 + Gemcitabine 1000mg/m2, IV on day 1, 8, 15 of 28 days cycle
| Arm | Type | Receives |
|---|---|---|
| Nivolumab+Gemcitabine | Experimental | Biological: Nivolumab, Drug: Nivolumab+GemcitabineNivolumab infusion on day 1 and 15 with the addition of gencitabine on day 1, 8 and 15 of 28 day cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Histologically confirmed diagnosis of non-small cell lung cancer (NSCLC). Patients should have stage IV disease (AJCC 7th edition), stage IIIb disease that is not amenable to potentially curative treatment (e.g. chemoradiotherapy) or unequivocal progression in a prior irradiated field. Measurable or evaluable disease is required.
- Fresh/ archived tumor tissue available for molecular marker testing is required for entry. A tumor block or at least 5 unstained slides must be available. As an alternative FFPE cell block that is sufficient for histologic analysis is acceptable. If a patient has had PD-L1 status previously determined with and FDA approved assay, they have met this requirement. Tissue is still requested (but not required) for further analysis
- Age > 18 years.
- ECOG performance status 0 or 1
- Patients must have normal organ and marrow functions as defined below:
Key exclusion criteria (14 listed)
- Patients with active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
- Patients requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Subjects are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if > 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
- As there is a potential for hepatic toxicity with nivolumab, drugs with predisposition to hepatotoxicity should be used with caution in patients treated with nivolumab-containing regimen.
- Patients are excluded if they have active brain metastases or leptomeningeal metastases. Subjects with brain metastases are eligible if metastases have been treated without clinical or radiologic evidence of progression for 14 days prior to initiation of treatment. An MRI within 14 days of commencing therapy is required for patients with a history of brain metastases.
- There must be no requirement for immunosuppressive doses of systemic corticosteroids (>10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration.
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 |
|---|---|---|
| NivolumabMonoclonal antibody against non small cell lung cancer | Biological | Nivolumab+Gemcitabine |
| Nivolumab+GemcitabineGemcitabine is added to the Nivolumab treatment | Drug | Nivolumab+Gemcitabine |
Primary outcome
Decrease in Macrophage Derived Suppressor Cells (MDSC) Numbers as a Result of Treatment With Gemcitabine.
Time frame: 2 years
Immunosuppression in terms of number of circulating MDSC in the blood by comparing within each arm reduction in the number of MDSCs after each cycle of treatment
1 secondary outcome
Increase in T-cell Activity
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab and Nivolumab+Gemcitabine in people with Non Small Cell Lung Cancer Stage IIIB, run by Fox Chase 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 16 inclusion and 14 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 28 Oct 2020. 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 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?
Yes. Results are posted in the registry (first posted 28 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Decrease in Macrophage Derived Suppressor Cells (MDSC) Numbers as a Result of Treatment With Gemcitabine. (time frame: 2 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 28 Oct 2020.