Advanced and Metastatic NSCLCPhase 3NCT06704620
Study of Tislelizumab and Platinum-based Chemotherapy Combination With H1 Receptor Antagonist（Diphenhydramine）in Advanced and Metastatic Non-Small Cell Lung Cancer
A Phase 3 study testing Diphenhydramine, Tislelizumab and Pemetrexed in people with Advanced and Metastatic NSCLC, run by Tianjin Medical University Cancer Institute and Hospital at 1 site in China.
Trial summary
The goal of this clinical trial is to learn if diphenhydramine can improve the effectiveness and decrease the toxicity for the treatment of advanced and metastatic Non-small cell lung cancer (NSCLC) with PD1 inhibitor plus chemotherapy. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Advanced and Metastatic NSCLC
- What is being tested?
- Diphenhydramine, Tislelizumab and Pemetrexed
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 430 participants
- Where
- 1 siteChina
- Study dates
- Dec 2024to Nov 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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
- Sign a written informed consent before implementing any procedures related to the trial;
- Age ≥18 years old and ≤75 years old;
- ECOG score 0 or 1;
- Expected survival time >3 months;
- Patients diagnosed with stage IIIB-IV NSCLC by imaging, tissue and/or cytology (according to AJCC 9th edition), or primary stage IIIB-IV NSCLC that relapses after surgery (if adjuvant therapy has been used, the drug must be discontinued for more than 6 months);Patients with IIIB/C are unable to undergo radical surgery or radiotherapy; Patients (adenocarcinoma and adenosquamous carcinoma) with wide type EGFR and negative ALK fusion gene can enroll into the trial;
- Not received systemic antitumor therapy before;
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- Included patients were intended to receive Tirellizumab combined with standard chemotherapy containing platinum. Squamous lung cancer patients should use Paclitarel for Injee in(Albumin Bound) plus platinum, non-squamous patients should use pemetrexed plus platinum;
- There was at least one radiographically measurable lesion according to the solid tumor efficacy evaluation criteria (RECIST version 1.1). Lesions located within the field of previous radiotherapy may be considered measurable if progression is demonstrated.
- The subject is allowed to receive palliative radiation therapy (including craniocerebral radiation therapy for symptomatic brain metastases) and radiation-related toxicities recover to less than or equal to degree 1(CTCAE 5.0, except hair loss).
- For adequate organ function, the subject must meet the following laboratory criteria:
- 1) The absolute value of neutrophil (ANC) ≥1.5x109/L in the past 14 days without the use of granulocyte colony-stimulating factor; 2) Platelets ≥100×109/L without blood transfusion in the past 14 days; 3) Hemoglobin >9g/dL in the last 14 days without blood transfusion or use of erythropoietin; 4) Total bilirubin ≤1.5 times the upper limit of normal (ULN) 5) Aspartate aminotransferase (AST), alanine aminotransferase (ALT) in ≤2.5 times ULN (subject with liver metastasis allowed ALT or AST ≤5×ULN); 6) Serum creatinine ≤1.5 times ULN and creatinine clearance (calculated by Cockcroft-Gault formula) ≥60 ml/min; 7) Good coagulation function, defined as international standardized ratio (INR) or prothrombin time (PT) ≤1.5 times ULN; 8) Normal thyroid function, defined as thyroid stimulating hormone (TSH) within the normal range. If baseline TSH is out of normal range, subjects whose total T3 (or FT3) and FT4 are within the normal range can also be enrolled; 9) Myocardial enzyme profiles within the normal range (laboratory abnormalities that are not clinically significant as determined by the investigator) are also allowed); 11. For female subjects of childbearing age, they should be administered for urine or blood pregnancy tests and the results should be negative within 3 days prior to the first study drug administration (day 1 of cycle 1). If the urine pregnancy test results cannot be confirmed as negative, blood pregnancy tests is required. Women of non-childbearing age were defined as at least one year after menopause or having undergone surgical sterilization or hysterectomy; 12. If there is a risk of pregnancy, all subjects (male or female) are required to take contraception with an annual failure rate of less than 1% was within 120 days after drug administration (or 180 days after last study drug administration) in the study for the entire duration of treatment until the end of treatment
Who cannot join
- Patients with lung metastasis of other primary malignant tumors;
- Patients with previous or concurrent malignant tumors of other systems (excluding basal cell carcinoma of skin and squamous dermatocarcinoma after radical treatment. and/or carcinoma in situ after radical resection);
- Patients received perioperative immunotherapy (preoperative neoadjuvant or postoperative adjuvant);
- With known driver gene mutations such as EGFR/ALK/ROS1;
- Patients with existing or previously diagnosed myasthenia gravis;
- Patients with existing or previously diagnosed angle-closure glaucoma;
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- Patients with existing or previously diagnosed prostatic hypertrophy;
- Patients were allergic to diphenhydramine and its excipients;
- Patients with pyloric-duodenal obstruction, pyloric stenosis caused by peptic ulcer, and bladder neck stenosis;
- Received radiation therapy prior to administration of the drug in the first study, meeting one of the following conditions:
- 1) ≥30% of bone marrow had received radiation therapy within 14 days prior to treatment 2) Received radiation therapy for lung lesions within 6 weeks prior to treatment with a dose >30Gy (Enrolled subjects must be safe from the toxicity of prior radiation therapy (Recover to grade 1 or below), no need for glucocorticoid therapy and no history of radiation pneumonia) 11. Patients are currently participating in an interventional clinical study treatment or has received another investigational drug or used research instrument therapy within 4 weeks prior to initial dosing.
- 12. Received proprietary Chinese medicines with anti-cancer indications or immunomodulatory effects (including thymosin, interferon, interleukin, except for local use to control pleural fluid) systemic treatment; 13. Patients have had active autoimmune diseases occurred within 2 years prior to first administration agents, which need for systemic treatment (e.g. use of disease-modifying drugs, glucocorticoids, or immunosuppression). Alternative therapies (e.g., thyroxine, insulin or for adrenal or pituitary machines) Incomplete physiological glucocorticoids, etc.) are not considered as systemic treatment; 14. Systemic glucocorticoid therapy (excluding nasal, inhalation, or other means for local use) was being received within 7 days prior to the first administration of the study) or any other form of immunosuppressive therapy; Note: Physiological doses of glucocorticoids are permitted (≤10 mg/ day of prednisone or equivalent); 15. There is clinically uncontrollable pleural effusion/abdominal effusion (Subjects no need to drain the effusion or no significant increase in effusion after 3 days of stopping drainage can be enrolled); 16. Known allogeneic organ transplantation (other than corneal transplantation) or allogeneic hematopoietic stem cell transplantation; 17. The patient has not fully recovered from the toxicity and/or complications caused by any intervention before starting treatment (i.e., ≤ grade 1 or in baseline, excluding weakness or hair loss); 18. Known history of human immunodeficiency virus (HIV) infection (i.e. HIV 1/2 antibody positive); 19. Untreated active hepatitis B (defined as HBsAg positive with a detectable HBV-DNA copy number greater than upper limit of normal value in cardiac laboratory);
- Note: Hepatitis B subjects who meet the following criteria can also be enrolled:
- HBV viral load <1000 copies /ml (200 IU/ml) prior to initial dosing, subjects should be treated with chemotherapy drugs throughout the study during this period, anti-HBV therapy is taken to avoid viral reactivation
- For subjects with anti-HBC (+), HBsAg (-), anti-HBS (-) and HBV viral load (-), no need to receive prophylactic anti-HBV therapy, but close monitoring of viral reactivation is required.
- 20. Active HCV-infected subjects (HCV antibody positive and HCV-RNA levels above the lower limit of detection); 21. Received live vaccine within 30 days prior to the first dose (cycle 1, day 1); Note: Injectable inactivated virus vaccine against seasonal influenza is permitted for 30 days prior to initial administration; But it is not allowed to receive intranasal live attenuated flu vaccine.
- 22. Pregnant or lactating women; 23. The presence of any serious or uncontrolled systemic disease, such as:
- There is a significant abnormality in the rhythm, conduction or morphology of the resting electrocardiogram with severe symptoms that are difficult to control, such as the complete left bundle branch conduction block, heart block above degree II, ventricular arrhythmia or atrial fibrillation;
- Unstable angina pectoris, congestive heart failure, New York Heart Association (NYHA) grade ≥ 2 chronic heart failure;
- Myocardial infarction occurred within 6 months before enrollment;
- Poor blood pressure control (systolic > 140 mmHg, diastolic > 90 mmHg);
- There is a history of non-infectious pneumonia requiring glucocorticoid therapy within 1 year prior to initial administration, or there is a current clinical activity interstitial lung disease;
- Active pulmonary tuberculosis;
- There is an active or uncontrolled infection that requires systemic treatment;
- Clinically active diverticulitis, abdominal abscess, gastrointestinal obstruction;
- Liver diseases such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis;
- Poor diabetes control (fasting blood glucose (FBG) > 10mmol/L);
- Urine routine indicated urine protein ≥++, and confirmed 24-hour urine protein quantity > 1.0 g;
- Subjects with mental disorders who are unable to cooperate with treatment; 24. Medical history or evidence of disease, treatment, or laboratory tests that may interfere with the test results or prevent the subject from participating fully in the study. The investigator considered the subjects with other potential risks unsuitable for participation in the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Tianjin Medical University Cancer Institute and Hospital
Tianjin
Liang Liu, M.D, Ph.D, 86-22-23340123 ext. 3172, liuliang@tjmuch.com
Xiubao Ren, M.D, Ph.D, 86-22-23340123 ext. 3173, renxiubao@tjmuch.com
About this study
Official title: Safety and Effectiveness of Tislelizumab and Platinum-based Chemotherapy Combination With H1 Receptor Antagonist（Diphenhydramine）in Advanced and Metastatic Non-Small Cell Lung Cancer: A Prospective, Randomized-controlled, Multi-center, Open-label, Phase-III Trial.
The goal of this clinical trial is to learn if diphenhydramine can improve the effectiveness and decrease the toxicity for the treatment of advanced and metastatic Non-small cell lung cancer (NSCLC) with PD1 inhibitor plus chemotherapy.
The main questions it aims to answer are:
Read more
- Dose diphenhydramine improve the effectiveness and survival of advanced and metastatic NSCLC treated with PD1 inhibitor and chemotherapy?
- Dose diphenhydramine decrease the toxicity of PD1 inhibitor plus platinum-based chemotherapy?
- Researchers will compare patients with or without diphenhydramine to see if diphenhydramine works to improve the effectiveness and decrease the toxicity.
Participants will:
- Take standard treatment (tislelizumab and platinum-based chemotherapy) with/without diphenhydramine（20mg qd d0-2）every cycle.
- Visit the clinic once every six weeks for checkups and tests
- Keep a diary of their symptoms and survival visit based on the protocol.
- Conditions
- Advanced and Metastatic NSCLC
- Being tested
- Diphenhydramine, Tislelizumab, Pemetrexed, Albumin paclitaxel, Carboplatin
- 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.
DiphenhydramineDrug
Diphenhydramine intramuscular injection 20mg qd d0-2 Q3W
TislelizumabDrug
Tislelizumab intravenous infusion 200mg d1
PemetrexedDrug
Pemetrexed intravenous infusion 500mg/m2 d1
Albumin paclitaxelDrug
Albumin paclitaxel intravenous infusion 260mg/m2 d1
CarboplatinDrug
Carboplatin intravenous infusion AUC5 d1
CisplatinDrug
Cisplatin intravenous infusion 75mg/m2 d1
| Study group | Role | What they receive |
|---|---|---|
| Arm1 | Experimental | Tislelizumab intravenous infusion 200mg d1; Pemetrexed intravenous infusion 500mg/m2 d1 or Albumin paclitaxel intravenous infusion 260mg/m2 d1; Carboplatin intravenous infusion AUC5 d1 or Cisplatin intravenous infusion 75mg/m2 d1; Diphenhydramine intramuscular injection 20mg qd d0-2 Q3W Receives: Drug: Diphenhydramine; Drug: Tislelizumab; Drug: Pemetrexed; Drug: Albumin paclitaxel; Drug: Carboplatin; Drug: Cisplatin |
| Arm2 | Active comparator | Tislelizumab intravenous infusion 200mg d1; Pemetrexed intravenous infusion 500mg/m2 d1 or Albumin paclitaxel intravenous infusion 260mg/m2 d1; Carboplatin intravenous infusion AUC5 d1 or Cisplatin intravenous infusion 75mg/m2 d1; Q3W Receives: Drug: Tislelizumab; Drug: Pemetrexed; Drug: Albumin paclitaxel; Drug: Carboplatin; Drug: Cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
PFS
From the initial treatment until the date of disease progression or the date of death from any cause, whichever occurred first
Measured: up to 24 months
Secondary outcomes (3)
ORR
ORR was defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR)
Measured: up to 24 months
OS
OS was the time from the initial treatment until the date of death from any cause
Measured: 3 years
Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events[Safety and Tolerability]
Adverse events were assessed according to the National Cancer Insti- tute Common Terminology Criteria for Adverse Events, version 5.0.
Measured: up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2024
- Study startDec 2024 (estimated)
- Primary completionNov 2026 (estimated)
- Study completionNov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced and Metastatic NSCLCStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 430 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tianjin Medical University Cancer Institute and Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Liang Liu, M.D,Ph.D, Principal investigator, Tianjin Medical University Cancer Institute and Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06704620
- Sponsor's protocol ID
- E20241045
- Status last verified
- Oct 2024
- First submitted
- 12 Nov 2024
- Last updated
- 16 Dec 2024
- Results posted
- 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 16 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Effectiveness of Tislelizumab and Platinum-based Chemotherapy Combination With H1 Receptor Antagonist（Diphenhydramine）in Advanced and Metastatic Non-Small Cell Lung Cancer: A Prospective, Randomized-controlled, Multi-center, Open-label, Phase-III Trial.
- ClinicalTrials.gov ID
- NCT06704620
- Acronym / sponsor ID
- E20241045
- Conditions
- Advanced and Metastatic NSCLC
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 430 participants (estimated)
- Lead sponsor
- Tianjin Medical University Cancer Institute and HospitalUniversity, hospital or other
- Study start
- Dec 2024 (estimated)
- Primary completion
- Nov 2026 (estimated)
- Study completion
- Nov 2027 (estimated)
- First posted
- 26 Nov 2024 (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.
The goal of this clinical trial is to learn if diphenhydramine can improve the effectiveness and decrease the toxicity for the treatment of advanced and metastatic Non-small cell lung cancer (NSCLC) with PD1 inhibitor plus chemotherapy.
The main questions it aims to answer are:
- Dose diphenhydramine improve the effectiveness and survival of advanced and metastatic NSCLC treated with PD1 inhibitor and chemotherapy?
- Dose diphenhydramine decrease the toxicity of PD1 inhibitor plus platinum-based chemotherapy?
- Researchers will compare patients with or without diphenhydramine to see if diphenhydramine works to improve the effectiveness and decrease the toxicity.
Participants will:
- Take standard treatment (tislelizumab and platinum-based chemotherapy) with/without diphenhydramine（20mg qd d0-2）every cycle.
- Visit the clinic once every six weeks for checkups and tests
- Keep a diary of their symptoms and survival visit based on the protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm1 | Experimental | Drug: Diphenhydramine, Drug: Tislelizumab, Drug: Pemetrexed, Drug: Albumin paclitaxel, Drug: Carboplatin, Drug: CisplatinTislelizumab intravenous infusion 200mg d1; Pemetrexed intravenous infusion 500mg/m2 d1 or Albumin paclitaxel intravenous infusion 260mg/m2 d1; Carboplatin intravenous infusion AUC5 d1 or Cisplatin intravenous infusion 75mg/m2 d1; Diphenhydramine intramuscular injection 20mg qd d0-2 Q3W |
| Arm2 | Active comparator | Drug: Tislelizumab, Drug: Pemetrexed, Drug: Albumin paclitaxel, Drug: Carboplatin, Drug: CisplatinTislelizumab intravenous infusion 200mg d1; Pemetrexed intravenous infusion 500mg/m2 d1 or Albumin paclitaxel intravenous infusion 260mg/m2 d1; Carboplatin intravenous infusion AUC5 d1 or Cisplatin intravenous infusion 75mg/m2 d1; Q3W |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Sign a written informed consent before implementing any procedures related to the trial;
- Age ≥18 years old and ≤75 years old;
- ECOG score 0 or 1;
- Expected survival time >3 months;
- Patients diagnosed with stage IIIB-IV NSCLC by imaging, tissue and/or cytology (according to AJCC 9th edition), or primary stage IIIB-IV NSCLC that relapses after surgery (if adjuvant therapy has been used, the drug must be discontinued for more than 6 months);Patients with IIIB/C are unable to undergo radical surgery or radiotherapy; Patients (adenocarcinoma and adenosquamous carcinoma) with wide type EGFR and negative ALK fusion gene can enroll into the trial;
Key exclusion criteria (29 listed)
- Patients with lung metastasis of other primary malignant tumors;
- Patients with previous or concurrent malignant tumors of other systems (excluding basal cell carcinoma of skin and squamous dermatocarcinoma after radical treatment. and/or carcinoma in situ after radical resection);
- Patients received perioperative immunotherapy (preoperative neoadjuvant or postoperative adjuvant);
- With known driver gene mutations such as EGFR/ALK/ROS1;
- Patients with existing or previously diagnosed myasthenia gravis;
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 |
|---|---|---|
| DiphenhydramineDiphenhydramine intramuscular injection 20mg qd d0-2 Q3W | Drug | Arm1 |
| TislelizumabTislelizumab intravenous infusion 200mg d1 | Drug | Arm1, Arm2 |
| PemetrexedPemetrexed intravenous infusion 500mg/m2 d1 | Drug | Arm1, Arm2 |
| Albumin paclitaxelAlbumin paclitaxel intravenous infusion 260mg/m2 d1 | Drug | Arm1, Arm2 |
| CarboplatinCarboplatin intravenous infusion AUC5 d1 | Drug | Arm1, Arm2 |
| CisplatinCisplatin intravenous infusion 75mg/m2 d1 | Drug | Arm1, Arm2 |
Primary outcome
PFS
Time frame: up to 24 months
From the initial treatment until the date of disease progression or the date of death from any cause, whichever occurred first
3 secondary outcomes
ORR
Time frame: up to 24 months
OS
Time frame: 3 years
Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events[Safety and Tolerability]
Time frame: up to 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2024.
- 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.
Liang Liu, M.D,Ph.D principal investigator
Tianjin Medical University Cancer Institute and Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Diphenhydramine, Tislelizumab and Pemetrexed in people with Advanced and Metastatic NSCLC, run by Tianjin Medical University Cancer Institute and Hospital 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 11 inclusion and 29 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: opening soon, as of the sponsor's last update on 16 Dec 2024. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Liang Liu, M.D, Ph.D (86-22-23340123 ext. 3172, liuliang@tjmuch.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PFS (time frame: up to 24 months). 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 16 Dec 2024.