Pulmonary Sarcomatoid CarcinomaPhase 2NCT04725448
Toripalimab Combined With Bevacizumab, Nab-paclitaxel and Carboplatin for Untreated Metastatic Pulmonary Sarcomatoid Carcinoma
A Phase 2 study testing Toripalimab, Bevacizumab and Nab-paclitaxel in people with Pulmonary Sarcomatoid Carcinoma and Non-small Cell Lung Cancer, run by Sichuan Cancer Hospital and Research Institute at 1 site in China.
Trial summary
This study aimed to evaluate the efficacy and safety of first-line Toripalimab combined with bevacizumab, nab-paclitaxel and carboplatin in the treatment of patients with advanced pulmonary sarcomatoid carcinoma. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Pulmonary Sarcomatoid Carcinoma, Non-small Cell Lung Cancer, Lung Diseases
- What is being tested?
- Toripalimab, Bevacizumab and Nab-paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteChina
- Study dates
- 6 Apr 2021to 30 Nov 2023
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1.18 to 75 years old, no gender limit;
- 2.ECOG PS: 0～2 points;
- 3.Untreated patients with stage IV pulmonary sarcomatoid carcinoma are staged according to the AJCC eighth edition non-small cell lung cancer staging standard;
- 4.Pulmonary sarcomatoid carcinoma confirmed by histopathology has at least one measurable lesion according to RECIST standard 1.1, and the lesion has not received radiotherapy;
- 5.The functions of important organs meet the following requirements (no blood components and cell growth factors are allowed to be used 2 weeks before the start of the research treatment) : Absolute Neutrophil Count (ANC) ≥1.5×10 E+9/L, Hemoglobin (HB) ≥9g/dL, Platelets (PLT)≥90×10 E+9/L, Serum Albumin (ALB)≥2.8g/dL, Total Bilirubin (TBIL) ≤1.5 ULN, ALT、AST≤2.5 UILN(If abnormal liver function is caused by liver metastasis, ≤5 ULN), Serum creatinine sCr≤1.5 ULN, endogenous creatinine clearance ≥50ml/min (Cockcroft-Gault formula) ,Normal thyroid function;
- 6.Expected survival time ≥ 3 months;
- 7.Female subjects with fertility should undergo a urine or serum pregnancy test within 72 hours before receiving the first study drug administration, and prove to be negative, and are willing to use effective during the test period to 3 months after the last administration Methods of contraception. For male subjects whose partners are women of childbearing age, effective methods of contraception should be used during the trial and within 3 months after the last administration;
- 8.The patients joined the study voluntarily and signed an informed consent form (ICF). They had good compliance and cooperated with follow-up.
Who cannot join
- 1.Patients with pathological types and primary lesions that do not meet the inclusion criteria;
- 2.There is known evidence that patients have mutations in any of the genes above EGFR, ROS-1, ALK, and c-MET;
- 3.Suffer from any active autoimmune diseases, such as interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism (can be included after hormone replacement therapy is normal);
- 4.Known to be allergic to other monoclonal macromolecular protein preparations, or to any of the components of Toripalimab;
- 5.Have received other PD-1 monoclonal antibody therapy or other immunotherapy against PD-1/PD-L1;
- 6.Active infection or fever of unknown origin occurred during the screening period and before the first administration>38.5℃ (according to the judgment of the investigator, the subject can be included in the group for fever caused by the tumor);
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- 7.Suffering from uncontrolled clinical symptoms or diseases of the heart, such as: (1) Heart failure above NYHA II; (2) Unstable angina pectoris; (3) Myocardial infarction occurred within 1 year; (4) Patients with clinically significant supraventricular or ventricular arrhythmia requiring clinical intervention.
- 8.Suffering from high blood pressure and cannot be well controlled by antihypertensive drugs (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg);
- 9.Abnormal coagulation function (INR>2.0, PT>16s), have bleeding tendency or are receiving thrombolytic therapy, and allow preventive use of low-dose aspirin and low-molecular-weight heparin;
- 10.Obvious coughing up blood or hemoptysis of 10ml or more per day in the 2 months before enrollment;
- 11.Have significant clinically significant bleeding symptoms or have a clear bleeding tendency within 3 months before enrollment;
- 12.Suffer from congenital or acquired immune function defects (such as HIV infection);
- 13.Received anti-tumor monoclonal antibody (mAb) within 4 weeks before the first use of the study drug, or the adverse event caused by the previously received drug has not recovered (ie ≤ grade 1 or reached the baseline level). Note: Except for subjects with ≤ Grade 2 neuropathy or ≤ Grade 2 hair loss, if the subject has undergone major surgery, the toxic reaction and/or complications caused by the surgical intervention must be fully recovered before starting treatment;
- 14.Live vaccines have been vaccinated within 4 weeks before the first use of the study drug. Inactivated virus vaccines for seasonal influenza and injection are allowed, but live attenuated influenza vaccines for nasal use are not allowed;
- 15.According to the judgment of the investigator, the subject has other factors that may cause him to be forced to terminate the study halfway, such as suffering from other serious diseases (including mental illness) requiring combined treatment, severely abnormal laboratory test values, family or social factors, It may affect the safety of subjects or the collection of experimental data;
- 16.The investigator judged other situations not suitable for inclusion in this study.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Sichuan Cancer Hospital
Chengdu, Sichuan/China, 610041
Juan Li, MD, +8613880276636, dr.lijuan@gmail.com
About this study
Official title: A Single-arm Exploratory Clinical Study on the Efficacy and Safety of Toripalimab Combined With Bevacizumab, Nab-paclitaxel and Carboplatin for Untreated Metastatic Pulmonary Sarcomatoid Carcinoma
This study aimed to evaluate the efficacy and safety of first-line Toripalimab combined with bevacizumab, nab-paclitaxel and carboplatin in the treatment of patients with advanced pulmonary sarcomatoid carcinoma.
Read the detailed description
Pulmonary sarcomatoid carcinoma(PSC) is a rare primary lung cancer, which belongs to the category of non-small cell lung cancer(NSCLC), accounting for about 0.3%-1.3% of lung cancers .Platinum-based combination chemotherapy is the standard adjuvant chemotherapy and palliative chemotherapy for NSCLC, and it is also commonly used for PSC. Advanced PSC has a low response rate to systemic chemotherapy and a short duration of curative effect. The primary progression rate of aggressive platinum-based chemotherapy is 60%-70%, showing that PSC is highly resistant to multiple chemotherapeutics. In recent years, the progress of targeting MET tyrosine kinase mutations has been relatively rapid, but most of the mutant PSCs targeting EGFR, KRAS, ALK, and BRAF V600E are case reports and there is no effective treatments. Immunotherapy has rewritten the treatment pattern of NSCLC. However, the current application of immunotherapy in PSC are mostly case reports. In immunotherapy, IMpower150 research data suggests that the combination of immunity and anti-angiogenesis + platinum-containing dual-agent chemotherapy can bring sustained OS benefits in NSCLC patients , and safety tolerated. However, PSC has moderate to high tumor mutation burden (TMB >10 mutations/Mb). This high mutation rate may increase tumor immunogenicity, making immunotherapy a better treatment option. At the same time, VEGF, as a cytokine that promotes the growth and differentiation of vascular endothelial cells, plays a decisive role in promoting tumor neovascularization. In this regard, immunotherapy combined with anti-angiogenesis and chemotherapy is worth exploring in the treatment of PSC.
- Conditions
- Pulmonary Sarcomatoid Carcinoma, Non-small Cell Lung Cancer, Lung Diseases, Thoracic Neoplasms
- Being tested
- Toripalimab, Bevacizumab, Nab-paclitaxel, Carboplatin
- Keywords
- PSC, NSCLC, Toripalimab, immunity therapy, Anti-angiogenesis, Platinum-containing dual-agent chemotherapy
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Lung Diseases, Thoracic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ToripalimabDrug
Also called JS001, Toripalimab Injection, TuoYI, Teruipuli Dankang
240mg, ivgtt, d1, every 3 weeks until disease progress or intolerable toxicity, up to 2 years of administration
BevacizumabDrug
Also called Bevacizumab Injection, Avastin, Bei Fa Zhu Dankang Zhusheye
7.5mg/kg, ivgtt, d1, every 3 weeks, up to 2 years of administration
Nab-paclitaxelDrug
Also called ABRAXANE, paclitaxel protein-bound particles for injectable suspension
260mg/m2,d1 or 130mg/m2,d1,8, ivgtt, every 3 weeks, up to 6 cycles
CarboplatinDrug
Also called Carboplatin injection
AUC=4～5, d1, ivgtt, every 3 weeks, up to 6 cycles
| Study group | Role | What they receive |
|---|---|---|
| Toripalimab Combined With Bevacizumab, Nab-paclitaxel and Carboplatin | Experimental | Drugs: Toripalimab, 240mg (6ml)/bottle, ivgtt, d1, q3w, administration until PD or death, the longest use time is two years.
Drugs: Bevacizumab, 7.5mg/kg, ivgtt, d1, q3w,the longest use time is two years.
Drugs: Nab-paclitaxel, 260mg/m2,ivgtt,d1 or 130mg/m2,ivgtt,d1,8, q3w, up to six cycles.
Drugs: Carboplatin, AUC=4～5, ivgtt, d1, q3w, up to six cycles. Receives: Drug: Toripalimab; Drug: Bevacizumab; Drug: Nab-paclitaxel; Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progress Free Survival(PFS)
It is defined as the time interval from randomization of patients to disease progression or death, whichever comes first. There was no progress or the time of disease progression was not recorded when the trial was withdrawn, and the date of the last examination was used as the end date.
Measured: up to 2 years
Secondary outcomes (5)
Overall response rate(ORR)
The proportion of patients with a best overall confirmed response of CR or PR in the whole body as assessed per RECIST 1.1 by the investigator.
Measured: up to 2 years
Disease Control Rate(DCR)
The proportion of patients with a best overall response of CR, PR or SD in the whole body, as assessed per RECIST 1.1 by the investigator.
Measured: up to 2 years
Overall Survival(OS)
Defined as the time interval from randomization to death. If the patient continues to survive or his life or death is unknown, the date of death will be reviewed using the latest point in time when the patient is still alive.
Measured: up to 2 years
Incidence of AEs
AEs per Common Terminology Criteria for Adverse Events (CTCAE V5.0)
Measured: up to 2 years
the quality of life (QoL)
Analysis of changes from baseline using the quality of life (QoL) instrument
Measured: up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2021
- Study start6 Apr 2021
- Primary completion1 Mar 2022 (estimated)
- Study completion30 Nov 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Sarcomatoid CarcinomaStudies 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
- 27 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sichuan Cancer Hospital and Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Juan LI, MD, Sichuan Cancer Hospital and Research Institute
- Investigators
- Juan Li, MD, Principal investigator, Sichuan Cancer Hospital and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04725448
- Sponsor's protocol ID
- JS001-ISS-CO200
- Status last verified
- Apr 2021
- First submitted
- 6 Jan 2021
- Last updated
- 6 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-arm Exploratory Clinical Study on the Efficacy and Safety of Toripalimab Combined With Bevacizumab, Nab-paclitaxel and Carboplatin for Untreated Metastatic Pulmonary Sarcomatoid Carcinoma
- ClinicalTrials.gov ID
- NCT04725448
- Acronym / sponsor ID
- JS001-ISS-CO200
- Conditions
- Pulmonary Sarcomatoid Carcinoma, Non-small Cell Lung Cancer, Lung Diseases, Thoracic Neoplasms
- Keywords
- PSC, NSCLC, Toripalimab, immunity therapy, Anti-angiogenesis, Platinum-containing dual-agent chemotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 27 participants (estimated)
- Lead sponsor
- Sichuan Cancer Hospital and Research InstituteUniversity, hospital or other
- Study start
- 6 Apr 2021 (actual)
- Primary completion
- 1 Mar 2022 (estimated)
- Study completion
- 30 Nov 2023 (estimated)
- First posted
- 26 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aimed to evaluate the efficacy and safety of first-line Toripalimab combined with bevacizumab, nab-paclitaxel and carboplatin in the treatment of patients with advanced pulmonary sarcomatoid carcinoma.
Detailed description
Pulmonary sarcomatoid carcinoma(PSC) is a rare primary lung cancer, which belongs to the category of non-small cell lung cancer(NSCLC), accounting for about 0.3%-1.3% of lung cancers .Platinum-based combination chemotherapy is the standard adjuvant chemotherapy and palliative chemotherapy for NSCLC, and it is also commonly used for PSC. Advanced PSC has a low response rate to systemic chemotherapy and a short duration of curative effect. The primary progression rate of aggressive platinum-based chemotherapy is 60%-70%, showing that PSC is highly resistant to multiple chemotherapeutics. In recent years, the progress of targeting MET tyrosine kinase mutations has been relatively rapid, but most of the mutant PSCs targeting EGFR, KRAS, ALK, and BRAF V600E are case reports and there is no effective treatments. Immunotherapy has rewritten the treatment pattern of NSCLC. However, the current application of immunotherapy in PSC are mostly case reports. In immunotherapy, IMpower150 research data suggests that the combination of immunity and anti-angiogenesis + platinum-containing dual-agent chemotherapy can bring sustained OS benefits in NSCLC patients , and safety tolerated. However, PSC has moderate to high tumor mutation burden (TMB >10 mutations/Mb). This high mutation rate may increase tumor immunogenicity, making immunotherapy a better treatment option. At the same time, VEGF, as a cytokine that promotes the growth and differentiation of vascular endothelial cells, plays a decisive role in promoting tumor neovascularization. In this regard, immunotherapy combined with anti-angiogenesis and chemotherapy is worth exploring in the treatment of PSC.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Toripalimab Combined With Bevacizumab, Nab-paclitaxel and Carboplatin | Experimental | Drug: Toripalimab, Drug: Bevacizumab, Drug: Nab-paclitaxel, Drug: CarboplatinDrugs: Toripalimab, 240mg (6ml)/bottle, ivgtt, d1, q3w, administration until PD or death, the longest use time is two years. Drugs: Bevacizumab, 7.5mg/kg, ivgtt, d1, q3w,the longest use time is two years. Drugs: Nab-paclitaxel, 260mg/m2,ivgtt,d1 or 130mg/m2,ivgtt,d1,8, q3w, up to six cycles. Drugs: Carboplatin, AUC=4～5, ivgtt, d1, q3w, up to six cycles. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 1.18 to 75 years old, no gender limit;
- 2.ECOG PS: 0～2 points;
- 3.Untreated patients with stage IV pulmonary sarcomatoid carcinoma are staged according to the AJCC eighth edition non-small cell lung cancer staging standard;
- 4.Pulmonary sarcomatoid carcinoma confirmed by histopathology has at least one measurable lesion according to RECIST standard 1.1, and the lesion has not received radiotherapy;
- 5.The functions of important organs meet the following requirements (no blood components and cell growth factors are allowed to be used 2 weeks before the start of the research treatment) : Absolute Neutrophil Count (ANC) ≥1.5×10 E+9/L, Hemoglobin (HB) ≥9g/dL, Platelets (PLT)≥90×10 E+9/L, Serum Albumin (ALB)≥2.8g/dL, Total Bilirubin (TBIL) ≤1.5 ULN, ALT、AST≤2.5 UILN(If abnormal liver function is caused by liver metastasis, ≤5 ULN), Serum creatinine sCr≤1.5 ULN, endogenous creatinine clearance ≥50ml/min (Cockcroft-Gault formula) ,Normal thyroid function;
Key exclusion criteria (16 listed)
- 1.Patients with pathological types and primary lesions that do not meet the inclusion criteria;
- 2.There is known evidence that patients have mutations in any of the genes above EGFR, ROS-1, ALK, and c-MET;
- 3.Suffer from any active autoimmune diseases, such as interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism (can be included after hormone replacement therapy is normal);
- 4.Known to be allergic to other monoclonal macromolecular protein preparations, or to any of the components of Toripalimab;
- 5.Have received other PD-1 monoclonal antibody therapy or other immunotherapy against PD-1/PD-L1;
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 |
|---|---|---|
| ToripalimabAlso: JS001, Toripalimab Injection, TuoYI, Teruipuli Dankang240mg, ivgtt, d1, every 3 weeks until disease progress or intolerable toxicity, up to 2 years of administration | Drug | Toripalimab Combined With Bevacizumab, Nab-paclitaxel and Carboplatin |
| BevacizumabAlso: Bevacizumab Injection, Avastin, Bei Fa Zhu Dankang Zhusheye7.5mg/kg, ivgtt, d1, every 3 weeks, up to 2 years of administration | Drug | Toripalimab Combined With Bevacizumab, Nab-paclitaxel and Carboplatin |
| Nab-paclitaxelAlso: ABRAXANE, paclitaxel protein-bound particles for injectable suspension260mg/m2,d1 or 130mg/m2,d1,8, ivgtt, every 3 weeks, up to 6 cycles | Drug | Toripalimab Combined With Bevacizumab, Nab-paclitaxel and Carboplatin |
| CarboplatinAlso: Carboplatin injectionAUC=4～5, d1, ivgtt, every 3 weeks, up to 6 cycles | Drug | Toripalimab Combined With Bevacizumab, Nab-paclitaxel and Carboplatin |
Primary outcome
Progress Free Survival(PFS)
Time frame: up to 2 years
It is defined as the time interval from randomization of patients to disease progression or death, whichever comes first. There was no progress or the time of disease progression was not recorded when the trial was withdrawn, and the date of the last examination was used as the end date.
5 secondary outcomes
Overall response rate(ORR)
Time frame: up to 2 years
Disease Control Rate(DCR)
Time frame: up to 2 years
Overall Survival(OS)
Time frame: up to 2 years
Incidence of AEs
Time frame: up to 2 years
the quality of life (QoL)
Time frame: up to 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2021.
- Individual participant dataSharing planned: No
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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.
Juan Li, MD principal investigator
Sichuan Cancer Hospital and Research Institute
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 Toripalimab, Bevacizumab and Nab-paclitaxel in people with Pulmonary Sarcomatoid Carcinoma and Non-small Cell Lung Cancer, run by Sichuan Cancer Hospital and Research Institute 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 8 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: status not confirmed, as of the sponsor's last update on 6 Apr 2021. 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 Juan Li, MD (+8613880276636, dr.lijuan@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progress Free Survival(PFS) (time frame: up to 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 6 Apr 2021.