Lung Cancer Stage IV，EGFR-mutant，TKI，PD-L1，SBRTPhase 2NCT04517526
Efficacy and Safety of Platinum-based Chemotherapy + Bevacizumab + Durvalumab, and Salvage SBRT for IV Non-Small Cell Lung Cancer Patients With EGFR Mutations After Failure of First Line Osimertinib: A Multicenter, Prospective, Phase II Clinical Study
A Phase 2 study testing pemetrexed，cisplatin/carboplatin，bevacizumab，durvalumab，SBRT in people with Lung Cancer Stage IV，EGFR-mutant，TKI，PD-L1，SBRT, run by Shanghai Cancer Hospital, China at 1 site in China.
Trial summary
Lung cancer still occupies the highest incidence and mortality rate in the wordwild, and non-small cell lung cancer (NSCLC) accounts for about 80% to 85% of all lung cancers. Currently, immune checkpoint inhibitors targeting PD-1/PD-L1 have become one of the new standard treatments for advanced NSCLC in some molecular… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Lung Cancer Stage IV，EGFR-mutant，TKI，PD-L1，SBRT
- What is being tested?
- pemetrexed，cisplatin/carboplatin，bevacizumab，durvalumab，SBRT
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteChina
- Study dates
- 1 Nov 2020to 1 Dec 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 and ≤ 75.
- Life expectancy exceeding 3 months.
- Histologic or cytologic pathology confirmed non-small cell lung cancer. However, sputum cytology results alone are not acceptable. The cytology results of tracheal swabbing, tracheal irrigation fluid and needle aspiration are acceptable.
- The investigator confirms the presence of at least one measurable lesion according to the RECIST 1.1 criteria.
- According to the International Association for the Study of Lung Cancer and the Joint Committee on American Cancer Classification, 8th Edition, TNM stage of lung cancer with histological or Advanced metastatic or recurrent (stage IV) cytologically proven inoperable and not amenable to radical concurrent radiotherapy or chemotherapy Patients with NSCLC.
- Eastern Oncology Collaborative Group (ECOG) fitness status score of 0 or 1.
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- Genetic testing suggests EGFR driver gene positivity, which can be accompanied by other driver gene positivity.
- Tumor progression or inability to tolerate chemotherapeutic response at the most recent evaluation following treatment with Osimertinib.
- Good hematopoiesis, defined as an absolute neutrophil count ≥1.5 × 109/L, platelet count ≥100 ×109/L，Erythropoietin ≥ 90 g/L [7 days without transfusion or erythropoietin (EPO-dependent).
- Good liver function, defined as total bilirubin levels ≤ 1.5 times the upper limit of normal (ULN); in patients without hepatic metastases, glutinous rice straw is used as a supplement.
- Aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 times ULN; for patients with documented liver metastases. AST and ALT levels ≤5 times ULN.
- Good renal function, defined as serum creatinine ≤ 1.5 times ULN or calculated creatinine clearance ≥ 60 ml/min (Cockcroft-Gault formula); less than 2+ urine protein on routine urinalysis, or 24-hour urine protein quantification <1 g.
- Good coagulation, defined as an International Standardized Ratio (INR) or Prothrombin Time (PT) ≤1.5 times ULN; if the subject is receiving anticoagulant therapy, provided that the PT is within the intended range of use of the anticoagulant.
- For female subjects of childbearing age, within 3 days prior to receiving the first study drug administration (Week 1, Day 1)A negative urine or serum pregnancy test is performed. If a negative urine pregnancy test cannot be confirmed, a blood pregnancy test may be ordered.
- High-performance contraception (i.e., methods with a failure rate of less than 1 per cent per year) for both male and female patients if there is a risk of conception.
Who cannot join
- NSCLC EGFR driver gene negativity.
- Pathological examination of a mixture of squamous or small cell lung cancer components.
- Currently participating in an interventional clinical research treatment or have received another investigational drug within 4 weeks prior to the first administration of the drug.
- Previous treatment with anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs or drugs that stimulate or synergistically inhibit another T-cell receptor (e.g., CTLA-4, OX-40, CD137), or radiation therapy in the chest and in metastatic lesions.
- Systemic systemic therapy with an anti-lung cancer indication with a proprietary Chinese medicine or immunomodulatory drug (including thymidine, interferon, interleukin, except for local use for pleural control) within 2 weeks prior to the first dose, or major surgery within 3 weeks prior to the first dose.
- Palliative radiotherapy completed within 7 days prior to the first administration of the drug.
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- Presence of clinically active diverticulitis, abdominal abscesses, gastrointestinal obstruction.
- Have received a transplant of a solid organ or blood system.
- Presence of clinically uncontrollable pleural effusion/abdominal fluid.
- Known severe allergic reaction (grade ≥3) to durvalumab, or other immunotherapeutic agents.
- Active autoimmune disease requiring systemic therapy (e.g., use of disease-modifying drugs, corticosteroids, or immunosuppressants) occurring within 2 years prior to the first dose of the drug. Alternative therapies (e.g., thyroxine, insulin, or physiologic corticosteroids for adrenal or pituitary insufficiency) are not considered systemic therapy.
- Diagnosis of immunodeficiency or being on systemic glucocorticoid therapy or any other form of immunosuppressive therapy within 7 days prior to the first administration of the study; physiological doses of glucocorticoids (≤10 mg/day of prednisone or equivalent) are permitted.
- Have not sufficiently recovered from toxicity and/or complications from any of the interventions prior to initiating treatment (i.e. ≤ grade 1 or at baseline, not including weakness or hair loss).
- Diagnosis of other malignancies within 5 years prior to the first dose, with exceptions including radically treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or radically resected carcinoma in situ.
- Symptomatic central nerve metastases. Patients with asymptomatic brain metastases or stable symptoms after treatment of brain metastatic lesions may be enrolled in this study if all of the following criteria are met: measurable lesions outside the central nervous system; absence of midbrain, bridge, cerebellum, medulla oblongata or spinal cord metastases; maintenance of clinical stability for at least 2 weeks; and cessation of hormonal therapy 3 days prior to the first dose of study drug.
- A history of non-infectious pneumonia requiring glucocorticoid therapy or current interstitial lung disease within 1 year prior to the first administration of the drug.
- Active infections that require systemic treatment.
- The known existence of a mental illness or substance abuse condition that may affect compliance with the test requirements.
- Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1/2 antibody positive).
- Note: Subjects with hepatitis B who meet the following criteria are also eligible for enrollment: HBV viral load must be <1000 copies/ml (200 IU/ml) prior to first dose and subjects should receive anti-HBV therapy to avoid viral reactivation throughout the duration of study chemotherapy drug therapy. Subjects with anti-HBc (+), HBsAg (-), anti-HB (-) and HBV viral load (-) do not need to receive prophylactic anti-HBV therapy but need to be monitored closely for viral reactivation.
- Active HCV-infected subjects (HCV antibody-positive and HCV-RNA levels above the lower limit of detection).
- Live vaccine within 30 days prior to first dose (Cycle 1, Day 1); NOTE: Injectable inactivated viral vaccine against seasonal influenza is allowed up to 30 days prior to first dose; however, live attenuated influenza vaccine for intranasal administration is not allowed.
- Evidence of a medical history or illness that could interfere with the results of the trial, prevent the subject from participating throughout the study, abnormal values for treatment or laboratory tests, or other circumstances that, in the opinion of the investigator, make enrollment unsuitable.
- Breastfeeding women.
Trial locations and contacts
1 site in 1 country.
China1 site
Fudan University shanghai cancer center
Shanghai, Shanghai Municipality, 200000
About this study
Official title: Efficacy and Safety of Platinum-based Chemotherapy + Bevacizumab + Durvalumab, and Salvage SBRT for IV Non-Small Cell Lung Cancer Patients With EGFR Mutations After Failure of First Line Osimertinib：A Multicenter, Prospective, Phase II Clinical Study
Lung cancer still occupies the highest incidence and mortality rate in the wordwild, and non-small cell lung cancer (NSCLC) accounts for about 80% to 85% of all lung cancers. Currently, immune checkpoint inhibitors targeting PD-1/PD-L1 have become one of the new standard treatments for advanced NSCLC in some molecular subtypes. In the Asian population, EGFR mutations are the most important molecular subtype in lung cancer patients, with an incidence of 39.6% in NSCLC and even more than 50% in adenocarcinoma. EGFR-TKIs are still the first-line treatment for advanced EGFR-mutant NSCLC and can induce a rapid response in this type of NSCLC, but acquired resistance usually occurs between 9 and 16-18 months (three generations of TKI), and the mechanism is complex. Subsequent treatment options are challenging. In contrast, immune checkpoint inhibitors have a specific role in improving the immune status of cancer patients, which may lead to sustained disease control. Clinical studies have shown that the regimen of pemetrexed/platinum-based chemotherapy combined with/PD-L1 inhibitors and bevacizumab has been effective in patients with EGFR-sensitive mutations. Preclinical and clinical studies have shown that EGFR-TKIs can modulate the tumor immune microenvironment and optimize the anti-tumor activity, thus enhancing the benefit of PD-1/PD-L1 inhibitors in patients with NSCLC. In addition, recent studies have shown that stereotactic body radiotherapy (SBRT/SRT) also performs well in the treatment of patients with stage IV NSCLC and can bring survival benefits to patients with advanced disease. We propose to design a prospective, multicenter, phase II clinical study of platinum-containing dual-drug chemotherapy + bevacizumab + SBRT/SRT for EGFR-mutant non-small cell lung cancer with first-line progression of Osimertinib, taking into account the current clinical research status. The Durvalumab regimen consists of 4 to 6 cycles of bevacizumab and/or Durvalumab maintenance therapy until disease progression, with stereotactic radiotherapy to oligoprogression sites, with the ultimate expectation of long-term survival benefit for this group of patients. The primary endpoints are PFS, overall OS, secondary endpoints are treatment-related toxicity, disease control rate, and exploratory endpoints are molecular markers of potential efficacy and toxicity,
- Being tested
- pemetrexed，cisplatin/carboplatin，bevacizumab，durvalumab，SBRT
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pemetrexed，cisplatin/carboplatin，bevacizumab，durvalumab，SBRTDrug
pemetrexed (500 mg/m2/d1) + cisplatin/carboplatin (20-25 mg/m2 × 3 days/AUC 5) + bevacizumab (7.5 mg/kg) + durvalumab (10 mg/kg) every 3 weeks for 4 to 6 cycles after informed consent, followed by bevacizumab and/or durvalumab anti-maintenance therapy until the emergence of what the investigator considers to be treatment-related toxicity or disease progression in the patient, followed by stereotactic radiotherapy to appropriate oligometastatic or oligoprogressive sites.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | pemetrexed (500 mg/m2/d1) + cisplatin/carboplatin (20-25 mg/m2 × 3 days/AUC 5) + bevacizumab (7.5 mg/kg) + durvalumab (10 mg/kg) every 3 weeks for 4 to 6 cycles , followed by bevacizumab and/or durvalumab anti-maintenance therapy until the emergence of treatment-related toxicity or disease progression in the patient, followed by stereotactic radiotherapy to appropriate oligometastatic or oligoprogressive sites Receives: Drug: pemetrexed，cisplatin/carboplatin，bevacizumab，durvalumab，SBRT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival (PFS)
the time between the start of treatment and the observation of disease progression or the occurrence of death from any cause, in this study there will be two stages of PFS available for analysis. Patients who are still alive at the time of analysis will have the date of their last contact as the cut-off date
Measured: 2 years
Overall survival (OS)
The time from the first day of enrolment to death from any cause, with the date of last contact for patients still alive at the time of analysis as the cut-off date.
Measured: 2 years
Secondary outcomes (2)
overall response rate (ORR)
overall remission rate
Measured: 2years
Duration of response（DOR)
duration of remission for all lesions after multi-drug combination therapy
Measured: 2years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2020
- Study start1 Nov 2020 (estimated)
- Primary completion1 Nov 2022 (estimated)
- Study completion1 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung Cancer Stage IV，EGFR-mutant，TKI，PD-L1，SBRTStudies 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
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Cancer Hospital, China
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04517526
- Sponsor's protocol ID
- CBDS-ZL
- Status last verified
- Aug 2020
- First submitted
- 16 Aug 2020
- Last updated
- 18 Aug 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Platinum-based Chemotherapy + Bevacizumab + Durvalumab, and Salvage SBRT for IV Non-Small Cell Lung Cancer Patients With EGFR Mutations After Failure of First Line Osimertinib：A Multicenter, Prospective, Phase II Clinical Study
- ClinicalTrials.gov ID
- NCT04517526
- Acronym / sponsor ID
- CBDS-ZL
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Shanghai Cancer Hospital, ChinaUniversity, hospital or other
- Study start
- 1 Nov 2020 (estimated)
- Primary completion
- 1 Nov 2022 (estimated)
- Study completion
- 1 Dec 2022 (estimated)
- First posted
- 18 Aug 2020 (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.
Lung cancer still occupies the highest incidence and mortality rate in the wordwild, and non-small cell lung cancer (NSCLC) accounts for about 80% to 85% of all lung cancers. Currently, immune checkpoint inhibitors targeting PD-1/PD-L1 have become one of the new standard treatments for advanced NSCLC in some molecular subtypes. In the Asian population, EGFR mutations are the most important molecular subtype in lung cancer patients, with an incidence of 39.6% in NSCLC and even more than 50% in adenocarcinoma. EGFR-TKIs are still the first-line treatment for advanced EGFR-mutant NSCLC and can induce a rapid response in this type of NSCLC, but acquired resistance usually occurs between 9 and 16-18 months (three generations of TKI), and the mechanism is complex. Subsequent treatment options are challenging. In contrast, immune checkpoint inhibitors have a specific role in improving the immune status of cancer patients, which may lead to sustained disease control. Clinical studies have shown that the regimen of pemetrexed/platinum-based chemotherapy combined with/PD-L1 inhibitors and bevacizumab has been effective in patients with EGFR-sensitive mutations. Preclinical and clinical studies have shown that EGFR-TKIs can modulate the tumor immune microenvironment and optimize the anti-tumor activity, thus enhancing the benefit of PD-1/PD-L1 inhibitors in patients with NSCLC. In addition, recent studies have shown that stereotactic body radiotherapy (SBRT/SRT) also performs well in the treatment of patients with stage IV NSCLC and can bring survival benefits to patients with advanced disease. We propose to design a prospective, multicenter, phase II clinical study of platinum-containing dual-drug chemotherapy + bevacizumab + SBRT/SRT for EGFR-mutant non-small cell lung cancer with first-line progression of Osimertinib, taking into account the current clinical research status. The Durvalumab regimen consists of 4 to 6 cycles of bevacizumab and/or Durvalumab maintenance therapy until disease progression, with stereotactic radiotherapy to oligoprogression sites, with the ultimate expectation of long-term survival benefit for this group of patients. The primary endpoints are PFS, overall OS, secondary endpoints are treatment-related toxicity, disease control rate, and exploratory endpoints are molecular markers of potential efficacy and toxicity,
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: pemetrexed，cisplatin/carboplatin，bevacizumab，durvalumab，SBRTpemetrexed (500 mg/m2/d1) + cisplatin/carboplatin (20-25 mg/m2 × 3 days/AUC 5) + bevacizumab (7.5 mg/kg) + durvalumab (10 mg/kg) every 3 weeks for 4 to 6 cycles , followed by bevacizumab and/or durvalumab anti-maintenance therapy until the emergence of treatment-related toxicity or disease progression in the patient, followed by stereotactic radiotherapy to appropriate oligometastatic or oligoprogressive sites |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Age ≥ 18 and ≤ 75.
- Life expectancy exceeding 3 months.
- Histologic or cytologic pathology confirmed non-small cell lung cancer. However, sputum cytology results alone are not acceptable. The cytology results of tracheal swabbing, tracheal irrigation fluid and needle aspiration are acceptable.
- The investigator confirms the presence of at least one measurable lesion according to the RECIST 1.1 criteria.
- According to the International Association for the Study of Lung Cancer and the Joint Committee on American Cancer Classification, 8th Edition, TNM stage of lung cancer with histological or Advanced metastatic or recurrent (stage IV) cytologically proven inoperable and not amenable to radical concurrent radiotherapy or chemotherapy Patients with NSCLC.
Key exclusion criteria (24 listed)
- NSCLC EGFR driver gene negativity.
- Pathological examination of a mixture of squamous or small cell lung cancer components.
- Currently participating in an interventional clinical research treatment or have received another investigational drug within 4 weeks prior to the first administration of the drug.
- Previous treatment with anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs or drugs that stimulate or synergistically inhibit another T-cell receptor (e.g., CTLA-4, OX-40, CD137), or radiation therapy in the chest and in metastatic lesions.
- Systemic systemic therapy with an anti-lung cancer indication with a proprietary Chinese medicine or immunomodulatory drug (including thymidine, interferon, interleukin, except for local use for pleural control) within 2 weeks prior to the first dose, or major surgery within 3 weeks prior to the first dose.
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 |
|---|---|---|
| pemetrexed，cisplatin/carboplatin，bevacizumab，durvalumab，SBRTpemetrexed (500 mg/m2/d1) + cisplatin/carboplatin (20-25 mg/m2 × 3 days/AUC 5) + bevacizumab (7.5 mg/kg) + durvalumab (10 mg/kg) every 3 weeks for 4 to 6 cycles after informed consent, followed by bevacizumab and/or durvalumab anti-maintenance therapy until the emergence of what the investigator considers to be treatment-related toxicity or disease progression in the patient, followed by stereotactic radiotherapy to appropriate oligometastatic or oligoprogressive sites. | Drug | 1 |
Primary outcome
Progression free survival (PFS)
Time frame: 2 years
the time between the start of treatment and the observation of disease progression or the occurrence of death from any cause, in this study there will be two stages of PFS available for analysis. Patients who are still alive at the time of analysis will have the date of their last contact as the cut-off date
Overall survival (OS)
Time frame: 2 years
The time from the first day of enrolment to death from any cause, with the date of last contact for patients still alive at the time of analysis as the cut-off date.
2 secondary outcomes
overall response rate (ORR)
Time frame: 2years
Duration of response（DOR)
Time frame: 2years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2020.
- Individual participant dataSharing planned: Undecided
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.
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 pemetrexed，cisplatin/carboplatin，bevacizumab，durvalumab，SBRT in people with Lung Cancer Stage IV，EGFR-mutant，TKI，PD-L1，SBRT, run by Shanghai Cancer Hospital, China at 1 site in China.
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 15 inclusion and 24 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 18 Aug 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 China. 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 MIN FAN, MASTER (+862164175590, fanming@fudan.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (PFS) (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2020.