Non-small Cell Lung CancerPhase 2NCT03808480
Nivolumab After Cyclophosphamide and Doxorubicin Induction Therapy in NSCLC With PD-L1<10%
A Phase 2 study testing CA and Nivolumab in people with Non-small Cell Lung Cancer, run by National Cancer Center, Korea at 1 site in South Korea.
Trial summary
Nivolumab is now the standard of care for second-line treatment of advanced squamous or nonsquamous NSCLC regardless of the tumor's expression of PD-1L. CheckMate057 trial results showed that in unselected patients with advanced or recurrent nonsquamous NSCLC who had stopped responding to a platinum-based chemotherapy… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer
- What is being tested?
- CA and Nivolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteSouth Korea
- Study dates
- 23 Jan 2019to 31 May 2022
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologic or cytologic diagnosis of nonsquamous NSCLC with SP263 PD-L1 expression <10%
- Patients whose tumor is not known to have anaplastic lymphoma kinase(ALK) or epidermal growth factor receptor(EGFR) mutation and Previously treated with at least one platinum-based chemotherapy but less than 3 prior chemotherapy
- Before study entry, a minimum of 21 days must have elapsed since any prior chemotherapy.
- Prior radiation therapy is allowed as long as the irradiated area is not the only source of measurable disease.
- No other forms of cancer therapy, such as immunotherapy for at least 2 weeks before the enrollment in study.
- Performance status of 0-1 on the ECOG criteria.
Show all 11Show fewer
- At least one unidimensionally measurable lesion meeting Response Evaluation Criteria in Solid Tumors (Revised RECIST guideline version 1.1)
- Estimated life expectancy of at least 8 weeks.
- Patient compliance that allow adequate follow-up. Adequate hematologic (WBC ≥4,000/mm3 또는 4.0 x 103/㎕ Platelet count ≥130,000mm3 또는 130 x 103/㎕ Bilirubin total ≤1.0 mg/dL AST/ALT≤ 80 IU/L creatinine concentration 1XULN or creatinine clearance (CrCl) > 50 mL/min (measured using the Cockcroft-Gault formula)
- Informed consent from patient or patient's relative.
- Males or females at least 18 years of age.
Who cannot join
- Previous therapy with anti-PD-1 or -PD-L1 inhibitors
- Persistence of clinically relevant therapy related toxicities from previous chemotherapy and/or radiotherapy
- Has received prior chemotherapy or tyrosine kinase inhibitor therapy within 3 weeks of the first dose of trial treatment ; completed palliative radiotherapy(except for brain and extremities) within 2weeks of the first dose of trial treatment. Prior curative thoracic radiation therapy(>=60Gy) is permitted if disease progression occured >4weeks after the completion of therapy.
- Treatment with other investigational drugs or treatment in another clinical trial within the past three weeks before start of therapy or concomitantly with this trial
- Has received a live vaccine(Concomitant yellow fever vaccin) within 4 weeks prior to the first administration of study medication. Concomitant yellow fever vaccination
- Active CNS metastases
Show all 23Show fewer
- Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for 2 weeks prior to randomization
- Leptomeningeal disease
- Significant cardiovascular diseases (i.e., hypertension not controlled by medical therapy, unstable angina, history of myocardial infarction within the past 12 months, congestive heart failure > NYHA II, serious cardiac arrhythmia, pericardial effusion)
- Proteinuria CTCAE grade 2 or greater
- Significant weight loss (> 10 %) within the past 6 weeks prior to treatment in the present trial
- Current peripheral neuropathy ≥ CTCAE(version4.0) Grade 2 except due to trauma
- Major injuries and/or surgery with incomplete wound healing within the past ten days prior to enrollment
- Serious infections requiring systemic antibiotic (e.g. antiviral, antimicrobial, antifungal) therapy
- Active hepatitis C and/or B infection
- Known human immunodeficiency virus (HIV) seropositivity
- Serious illness or concomitant non-oncological disease such as neurologic-,psychiatric-, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study
- Patients who are sexually active and unwilling to use a medically acceptable method of contraception (e.g. such as implants, injectables, combined oral contraceptives, some intrauterine devices or vasectomized partner for participating females, condoms for participating males) during the trial and for at least 7 months after end of active therapy
- Pregnancy or breast feeding
- Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule
- Patients unable to comply with the protocol
- Active alcohol or drug abuse
- Other malignancy within the past three years other than basal cell skin cancer or carcinoma in situ of the cervix
Trial locations and contacts
1 site in 1 country.
South Korea1 site, 1 recruiting
- Recruiting
National Cancer Center
Goyang-si, Gyeonggi-do, 10408
Ji-Youn Han, Ph.D, +82-31-920-1210, jymama@ncc.re.kr
Sehee Oh, +82-31-920-0398, oshee97@ncc.re.kr
About this study
Official title: Nivolumab After Cyclophosphamide and Doxorubicin(CA) Induction Therapy in Previously Treated Advanced Non-squamous Cell Non-small Cell Lung Cancer With PD-L1<10%
Nivolumab is now the standard of care for second-line treatment of advanced squamous or nonsquamous NSCLC regardless of the tumor's expression of PD-1L. CheckMate057 trial results showed that in unselected patients with advanced or recurrent nonsquamous NSCLC who had stopped responding to a platinum-based chemotherapy regimen, treatment with nivolumab produced significantly better overall survival during follow-up as long as 18 months, compared with a docetaxel-based regimen. But during the first 3 months on randomized treatment, 15 more patients died in the nivolumab arm than in the docetaxel arm. This quickly reversed during months 4-6 on treatment, when nine more patients died on docetaxel than on nivolumab. A post hoc analysis showed a trend to a higher risk for death during the first 3 months of nivolumab treatment among patients with poorer prognostic features, more aggressive disease, and low or no tumor expression of PD-L1. In addition, only a subgroup of patients benefits from nivolumab with response rates of 20% in unselected cohorts and 10% in low PD-L1 expression cohort. Strategies to render the tumor micro-environment (TME) more susceptible to anti-PD1 might include stimulation of anti-cancer immune responses by induction treatment with low dose chemotherapy.
Given the potent immune-modulating effects and anti-tumor activity of cyclophosphamide and doxorubicin, Investigator propose a study of combining nivolumab with induction therapy with cyclophosphamide and doxorubicin for nonsquamous NSCLC with PD-L1 expression less than 10%.
Read the detailed description
Nivolumab is now the standard of care for second-line treatment of advanced squamous or nonsquamous non-small cell lung cancer (NSCLC) regardless of the tumor's expression of programmed death-1 ligand (PD-1L). The 2015 Food and Drug Administration approval cited results from the Open-Label Randomized Phase III Trial of Nivolumab Versus Docetaxel in Previously Treated Metastatic nonsquamous-NSCLC (CheckMate057) trial. Those results showed that in unselected patients with advanced or recurrent nonsquamous NSCLC who had stopped responding to a platinum-based chemotherapy regimen, treatment with nivolumab produced significantly better overall survival during follow-up as long as 18 months, compared with a docetaxel-based regimen. But a more detailed assessment of the survival data showed an unexpected pattern of an early hazard among the nivolumab patients. During the first 3 months on randomized treatment, 15 more patients died in the nivolumab arm than in the docetaxel arm. This quickly reversed during months 4-6 on treatment, when nine more patients died on docetaxel than on nivolumab. By 12 months after the onset of treatment, overall survival was 51% in the nivolumab group and 39% among those randomized to docetaxel. A post hoc analysis showed a trend to a higher risk for death during the first 3 months of nivolumab treatment among patients with poorer prognostic features, more aggressive disease, and low or no tumor expression of PD-L1. In addition, only a subgroup of patients benefits from nivolumab with response rates of 20% in unselected cohorts and 10% in low PD-L1 expression cohort. Strategies to render the tumor micro-environment (TME) more susceptible to anti-PD1 might include stimulation of anti-cancer immune responses by induction treatment with low dose chemotherapy.
Cyclophosphamide, an old-school chemotherapeutic agent used across a wide range of malignancies, was found to be a potent immune modulator that targets suppressive regulatory immune cells within the tumor microenvironment while enhancing effector cells. However, cyclophosphamide has a limited effect on TIL from tumors larger than a few mm diameter in view of an increased percentage of myeloid derived suppressor cells (MDSC). Meanwhile, doxorubicin is also has a potent immune-modulating activity, which can selectively impair MDSC-induced immunosuppression. Additionally, both cyclophosphamide and doxorubicin have anti-tumor activity against NSCLC. Given the potent immune-modulating effects and anti-tumor activity of cyclophosphamide and doxorubicin, Investigator propose a study of combining nivolumab with induction therapy with cyclophosphamide and doxorubicin for nonsquamous NSCLC with PD-L1 expression less than 10%.
- Conditions
- Non-small Cell Lung Cancer
- Being tested
- CA and Nivolumab
- 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.
CA and NivolumabDrug
Also called Opdivo
Cyclophosphamide 500mg/m2 IV on D1 (C1-4), 1cycle=21days) Doxorubicin 50mg/m2 IV on D1 (C1~4, 1cycle=21days) Nivolumab 360 mg/IV C2~4 D1 (1cycle=21days) Nivolumab 400mg/IV on D1 from Cycle 5 every 4 weeks.
| Study group | Role | What they receive |
|---|---|---|
| CA and Nivolumab | Experimental | After 1 cycle of cyclophosphamide and doxorubicin (CA) induction therapy, Nivolumab 360mg flat dose will be given on day 1 with CA chemotherapy in a 21-day cycle.
After the completion of 4 cycles of CA chemotherapy, Nivolumab will be continued as a single agent at a dose of 480mg flat dose every 4 weeks until loss of clinical benefit Receives: Drug: CA and Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
objective response
objective response rate using RECIST v1.1
Measured: From date of first administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2019
- Study start23 Jan 2019
- Primary completion31 May 2022 (estimated)
- Study completion31 May 2022 (estimated)
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Center, Korea
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Ji-youn Han, National Cancer Center, Korea
- Investigators
- Ji-youn han, Ph.D, Principal investigator, National Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03808480
- Sponsor's protocol ID
- NCC2018-0267
- Status last verified
- Apr 2022
- First submitted
- 26 Dec 2018
- Last updated
- 6 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nivolumab After Cyclophosphamide and Doxorubicin(CA) Induction Therapy in Previously Treated Advanced Non-squamous Cell Non-small Cell Lung Cancer With PD-L1<10%
- ClinicalTrials.gov ID
- NCT03808480
- Acronym / sponsor ID
- NCC2018-0267
- Conditions
- Non-small Cell Lung Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 22 participants (estimated)
- Lead sponsor
- National Cancer Center, KoreaOther government
- Study start
- 23 Jan 2019 (actual)
- Primary completion
- 31 May 2022 (estimated)
- Study completion
- 31 May 2022 (estimated)
- First posted
- 17 Jan 2019 (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.
Nivolumab is now the standard of care for second-line treatment of advanced squamous or nonsquamous NSCLC regardless of the tumor's expression of PD-1L. CheckMate057 trial results showed that in unselected patients with advanced or recurrent nonsquamous NSCLC who had stopped responding to a platinum-based chemotherapy regimen, treatment with nivolumab produced significantly better overall survival during follow-up as long as 18 months, compared with a docetaxel-based regimen. But during the first 3 months on randomized treatment, 15 more patients died in the nivolumab arm than in the docetaxel arm. This quickly reversed during months 4-6 on treatment, when nine more patients died on docetaxel than on nivolumab. A post hoc analysis showed a trend to a higher risk for death during the first 3 months of nivolumab treatment among patients with poorer prognostic features, more aggressive disease, and low or no tumor expression of PD-L1. In addition, only a subgroup of patients benefits from nivolumab with response rates of 20% in unselected cohorts and 10% in low PD-L1 expression cohort. Strategies to render the tumor micro-environment (TME) more susceptible to anti-PD1 might include stimulation of anti-cancer immune responses by induction treatment with low dose chemotherapy.
Given the potent immune-modulating effects and anti-tumor activity of cyclophosphamide and doxorubicin, Investigator propose a study of combining nivolumab with induction therapy with cyclophosphamide and doxorubicin for nonsquamous NSCLC with PD-L1 expression less than 10%.
Detailed description
Nivolumab is now the standard of care for second-line treatment of advanced squamous or nonsquamous non-small cell lung cancer (NSCLC) regardless of the tumor's expression of programmed death-1 ligand (PD-1L). The 2015 Food and Drug Administration approval cited results from the Open-Label Randomized Phase III Trial of Nivolumab Versus Docetaxel in Previously Treated Metastatic nonsquamous-NSCLC (CheckMate057) trial. Those results showed that in unselected patients with advanced or recurrent nonsquamous NSCLC who had stopped responding to a platinum-based chemotherapy regimen, treatment with nivolumab produced significantly better overall survival during follow-up as long as 18 months, compared with a docetaxel-based regimen. But a more detailed assessment of the survival data showed an unexpected pattern of an early hazard among the nivolumab patients. During the first 3 months on randomized treatment, 15 more patients died in the nivolumab arm than in the docetaxel arm. This quickly reversed during months 4-6 on treatment, when nine more patients died on docetaxel than on nivolumab. By 12 months after the onset of treatment, overall survival was 51% in the nivolumab group and 39% among those randomized to docetaxel. A post hoc analysis showed a trend to a higher risk for death during the first 3 months of nivolumab treatment among patients with poorer prognostic features, more aggressive disease, and low or no tumor expression of PD-L1. In addition, only a subgroup of patients benefits from nivolumab with response rates of 20% in unselected cohorts and 10% in low PD-L1 expression cohort. Strategies to render the tumor micro-environment (TME) more susceptible to anti-PD1 might include stimulation of anti-cancer immune responses by induction treatment with low dose chemotherapy.
Cyclophosphamide, an old-school chemotherapeutic agent used across a wide range of malignancies, was found to be a potent immune modulator that targets suppressive regulatory immune cells within the tumor microenvironment while enhancing effector cells. However, cyclophosphamide has a limited effect on TIL from tumors larger than a few mm diameter in view of an increased percentage of myeloid derived suppressor cells (MDSC). Meanwhile, doxorubicin is also has a potent immune-modulating activity, which can selectively impair MDSC-induced immunosuppression. Additionally, both cyclophosphamide and doxorubicin have anti-tumor activity against NSCLC. Given the potent immune-modulating effects and anti-tumor activity of cyclophosphamide and doxorubicin, Investigator propose a study of combining nivolumab with induction therapy with cyclophosphamide and doxorubicin for nonsquamous NSCLC with PD-L1 expression less than 10%.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CA and Nivolumab | Experimental | Drug: CA and NivolumabAfter 1 cycle of cyclophosphamide and doxorubicin (CA) induction therapy, Nivolumab 360mg flat dose will be given on day 1 with CA chemotherapy in a 21-day cycle. After the completion of 4 cycles of CA chemotherapy, Nivolumab will be continued as a single agent at a dose of 480mg flat dose every 4 weeks until loss of clinical benefit |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Histologic or cytologic diagnosis of nonsquamous NSCLC with SP263 PD-L1 expression <10%
- Patients whose tumor is not known to have anaplastic lymphoma kinase(ALK) or epidermal growth factor receptor(EGFR) mutation and Previously treated with at least one platinum-based chemotherapy but less than 3 prior chemotherapy
- Before study entry, a minimum of 21 days must have elapsed since any prior chemotherapy.
- Prior radiation therapy is allowed as long as the irradiated area is not the only source of measurable disease.
- No other forms of cancer therapy, such as immunotherapy for at least 2 weeks before the enrollment in study.
Key exclusion criteria (23 listed)
- Previous therapy with anti-PD-1 or -PD-L1 inhibitors
- Persistence of clinically relevant therapy related toxicities from previous chemotherapy and/or radiotherapy
- Has received prior chemotherapy or tyrosine kinase inhibitor therapy within 3 weeks of the first dose of trial treatment ; completed palliative radiotherapy(except for brain and extremities) within 2weeks of the first dose of trial treatment. Prior curative thoracic radiation therapy(>=60Gy) is permitted if disease progression occured >4weeks after the completion of therapy.
- Treatment with other investigational drugs or treatment in another clinical trial within the past three weeks before start of therapy or concomitantly with this trial
- Has received a live vaccine(Concomitant yellow fever vaccin) within 4 weeks prior to the first administration of study medication. Concomitant yellow fever vaccination
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 |
|---|---|---|
| CA and NivolumabAlso: OpdivoCyclophosphamide 500mg/m2 IV on D1 (C1-4), 1cycle=21days) Doxorubicin 50mg/m2 IV on D1 (C1~4, 1cycle=21days) Nivolumab 360 mg/IV C2~4 D1 (1cycle=21days) Nivolumab 400mg/IV on D1 from Cycle 5 every 4 weeks. | Drug | CA and Nivolumab |
Primary outcome
objective response
Time frame: From date of first administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48months
objective response rate using RECIST v1.1
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2022.
- Individual participant dataSharing planned: No
Related trials for Non-small Cell Lung Cancer
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
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.
Ji-youn han, Ph.D principal investigator
National 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 2 study testing CA and Nivolumab in people with Non-small Cell Lung Cancer, run by National Cancer Center, Korea at 1 site in South Korea.
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 11 inclusion and 23 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: status not confirmed, as of the sponsor's last update on 6 Apr 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 South Korea. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ji-youn Han, Ph.D (82-31-920-1210, jymama@ncc.re.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
objective response (time frame: From date of first administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48months). 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 6 Apr 2022.