Lung CancerPhase 2NCT06492421
Neoadjuvant Intra-tumor Double Immunotherapy for Lung Cancer.
A Phase 2 study testing ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumab in people with Lung Cancer and Surgery, run by Second Affiliated Hospital of Guangzhou Medical University at 1 site in China.
Trial summary
This phase II trial studies how well intra-tumor injection of double checkpoint inhibitors work when given alone and in combination with chemotherapy or/and bevacizumab in treating patients with previously untreated stage I-IIIA non-small cell lung cancer. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Lung Cancer, Surgery, Non-small Cell Lung Cancer
- What is being tested?
- ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteChina
- Study dates
- 1 Jul 2024to 30 Dec 2035
- Phase
- Phase 2
- 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
- Histologically or cytologically confirmed previously untreated non-small cell lung cancer. If a diagnostic biopsy is available, a pre-treatment biopsy is not required. Patients with a suspected lung cancer are eligible, but pathology must be confirmed prior to initiating treatment on study.
- Patients with stage IIIA must not have more than one mediastinal lymph node station involved by tumor.
- All patients must have lymph node evaluation of contralateral stations 2 and/or 4 to exclude N3 disease.
- The patient must be a suitable candidate for surgery, in the opinion of the treating physician.
- Signed and dated written informed consent must be provided by the patient prior to admission to the study in accordance with International Conference on Harmonization-Good Clinical Practice (ICH-GCP) guidelines and to the local legislation.
- Eastern Cooperative Oncology Group (ECOG) performance status score 0-1.
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L; Hemoglobin >= 8.0 g/dL; Platelets >= 100 x 10^9/L; Total bilirubin =< 1.5 x upper limit of normal (ULN) (except subjects with Gilbert syndrome who can have total bilirubin < 3.0 mg/dL); Creatinine =< 1.5 x ULN or calculated creatinine clearance >= 50 mL/min using Cockcroft-Gault formula for creatinine clearance calculation OR 24-hour urine creatinine clearance >= 50 mL/min.
Who cannot join
- Prior systemic therapy or radiation therapy for treatment of the current lung cancer.
- Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy) or investigational anti-cancer drug.
- Pregnant or lactating female.
- Unwillingness or inability to follow the procedures required in the protocol.
- Patients with pre-existing sensorineural hearing impairment/loss or newly diagnosed as documented by an audiology assessment performed prior to study enrollment may not be eligible for cisplatin and may be dispositioned to carboplatin, as determined by the treating physician.
- Patients with a history of severe hypersensitivity reaction to taxotere and or polysorbate 80 must be excluded.
Show all 18Show fewer
- Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
- Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Subjects are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if > 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
- Prior treatment with an anti-PD-1, anti-PD-L1 or anti-CTLA-4 antibody.
- Known positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid indicating acute or chronic infection.
- Known history of testing positive for human immunodeficiency virus or known acquired immunodeficiency syndrome.
- History of severe hypersensitivity reaction to any monoclonal antibody and/or to study drug components.
- Serious illness or concomitant non-oncological disease such as neurologic, psychiatric, infectious disease 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.
- Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule.
- Allergic to contrast agent.
- Any agents which could affect the absorption or pharmacokinetics of the study drugs.
- Other conditions that investigator decides not suitable for the trial.
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, 1 recruiting
- Recruiting
The Second Affiliated Hospital of Guangzhou Medical University
Guanzhou, Guangdong, 51260
Zhenfeng Zhang, MD,PhD, 02034153532, zhangzhf@gzhmu.edu.cn
About this study
Official title: Phase II Study of Neoadjuvant CT-Guided Intra-tumor Double Checkpoint Blockades for Untreated Stage I-IIIA Non-Small Cell Lung Cancers Amenable for Surgical Resection
This phase II trial studies how well intra-tumor injection of double checkpoint inhibitors work when given alone and in combination with chemotherapy or/and bevacizumab in treating patients with previously untreated stage I-IIIA non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as ipilimumab, pembrolizumab or durvalumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Drugs used in interventional radiological chemotherapy, such as idabubicin, can directly kill the cancer cell and release tumor antigens to activate DC function in situ. Giving intra-tumor injection of checkpoints inhibitors with or without chemotherapy and/or bevecizumab may work better than in vein infusion of the drugs in treating patients with non-small cell lung cancer.
Read the detailed description
Antibodies against CTLA4, PD1 or PDL1 are representative drugs for the check-points inhibitory agents, and their clinical indications have been approved in various types of tumors, including advanced melanoma, non-small cell lung cancer, renal cell carcinoma, and classical Hodgkin's lymphoma and late recurrent head and neck squamous cell carcinoma patients, et al. Those drugs are regularly systemically administrated by vein infusion, however, local delivery of those drugs via interventional radiology technique including trans-artery or intra-tumor injection may increase the local drug concentration of the tumor, improve the efficacy, and reduce systemic adverse reactions. CTLA4 antibody ipilimumab has been widely effectively using to combine with PD1 or PDL1 antibody and this study is to combine ipilimumab and PD1 antibody or PDL1 antibody, so called double checkpoint inhibitors combination therapy, as neoadjuvant therapy for NSCLC via intra-tumor admistration. To the investigator's knowledge, no studies have been developed on the safety, efficacy and survival benefit of the double checkpoint inhibitors combination therapy for cancer patients as neoadjuvant treatment via intra-tumor delivery. This phase II clinical trial is designed to assess the safety and survival benefit of ipilimumab and pembrolizumab or durvalumab combination with or without chemodrug and/or bevacizumab as neoaduvant therapy on patients with NSCLC, including safety, pCR, mPR, PFS, ORR, DCR, and median survival time.
- Conditions
- Lung Cancer, Surgery, Non-small Cell Lung Cancer
- Being tested
- ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumab
- Keywords
- NSCLC, Intra-tumor injection, Neoadjuvant therapy, Double immunotherapy, Interventional radiology, Bevacizumab
- Medical subject headings
- Lung Neoplasms, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumabDrug
Also called Other ICIs
This study has 3 subgroups:
Arm 1. Ipilimumab +pembrolizumab or Ipilimumab +durvalumab is administrated with a total dose of 1-2mg/kg via intra-tumor fine needle injection in 10 min, every 3 weeks, total 3-4 times.
Arm 2. Ipilimumab +pembrolizumab or Ipilimumab +durvalumab combined with idarubicin is administrated via intra-tumor fine needle injection in 15 min, every 3 weeks, total 3-4 times.
Arm 3. Ipilimumab +pembrolizumab or Ipilimumab +durvalumab combined with idarubicin plus bevacizumab is administrated via intra-tumor fine needle injection in 20 min, every 3 weeks, total 3-4 times.
| Study group | Role | What they receive |
|---|---|---|
| Group 1: IT injection of double ICIs | Experimental | Neoadjuvant therapy: intra-tumor injection of double ICIs only. Receives: Drug: ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumab |
| Group 2: IT injection of double ICIs and chemodrug | Experimental | Neoadjuvant therapy: intra-tumor injection of double ICIs and chemodrug. Receives: Drug: ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumab |
| Group 3: IT injection of double ICIs and chemodrug plus bevacizumab | Experimental | Neoadjuvant therapy: intra-tumor injection of double ICIs and chemodrug plus bevacizumab. Receives: Drug: ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
pCR rate for the study groups
Pathologic complete response (pCR) is defined as after neoadjuvant therapy, the surgical specimen can not find any residual cancer cells.
Measured: Six months
mPR rate for the study groups
Major pathologic response (MPR) is defined as pathological less than 10% survival cancer cells after tumor resection.
Measured: Six months
Secondary outcomes (3)
Toxicity of the study groups
Toxicity is assessed by the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 4.
Measured: Six months
Response rates to neoadjuvant treatment
Recurrence-free survival is measured as routine.
Measured: Six years
Overall survival
To correlate major pathologic response with recurrence-free and overall survival.
Measured: Six years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2024
- Study start1 Jul 2024
- Primary completion30 Dec 2028 (estimated)
- Study completion30 Dec 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- More trials run by Second Affiliated Hospital of Guangzhou Medical UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Zhenfeng Zhang, MD, PhD, Principal investigator, Second Affiliated Hospital of Guangzhou Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06492421
- Sponsor's protocol ID
- ZZ-IT-ICIs-LC-Neoadjuvant-028
- Status last verified
- Jul 2024
- First submitted
- 2 Jul 2024
- Last updated
- 9 Jul 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Neoadjuvant CT-Guided Intra-tumor Double Checkpoint Blockades for Untreated Stage I-IIIA Non-Small Cell Lung Cancers Amenable for Surgical Resection
- ClinicalTrials.gov ID
- NCT06492421
- Acronym / sponsor ID
- ZZ-IT-ICIs-LC-Neoadjuvant-028
- Conditions
- Lung Cancer, Surgery, Non-small Cell Lung Cancer
- Keywords
- NSCLC, Intra-tumor injection, Neoadjuvant therapy, Double immunotherapy, Interventional radiology, Bevacizumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital of Guangzhou Medical UniversityUniversity, hospital or other
- Study start
- 1 Jul 2024 (actual)
- Primary completion
- 30 Dec 2028 (estimated)
- Study completion
- 30 Dec 2035 (estimated)
- First posted
- 9 Jul 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.
This phase II trial studies how well intra-tumor injection of double checkpoint inhibitors work when given alone and in combination with chemotherapy or/and bevacizumab in treating patients with previously untreated stage I-IIIA non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as ipilimumab, pembrolizumab or durvalumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Drugs used in interventional radiological chemotherapy, such as idabubicin, can directly kill the cancer cell and release tumor antigens to activate DC function in situ. Giving intra-tumor injection of checkpoints inhibitors with or without chemotherapy and/or bevecizumab may work better than in vein infusion of the drugs in treating patients with non-small cell lung cancer.
Detailed description
Antibodies against CTLA4, PD1 or PDL1 are representative drugs for the check-points inhibitory agents, and their clinical indications have been approved in various types of tumors, including advanced melanoma, non-small cell lung cancer, renal cell carcinoma, and classical Hodgkin's lymphoma and late recurrent head and neck squamous cell carcinoma patients, et al. Those drugs are regularly systemically administrated by vein infusion, however, local delivery of those drugs via interventional radiology technique including trans-artery or intra-tumor injection may increase the local drug concentration of the tumor, improve the efficacy, and reduce systemic adverse reactions. CTLA4 antibody ipilimumab has been widely effectively using to combine with PD1 or PDL1 antibody and this study is to combine ipilimumab and PD1 antibody or PDL1 antibody, so called double checkpoint inhibitors combination therapy, as neoadjuvant therapy for NSCLC via intra-tumor admistration. To the investigator's knowledge, no studies have been developed on the safety, efficacy and survival benefit of the double checkpoint inhibitors combination therapy for cancer patients as neoadjuvant treatment via intra-tumor delivery. This phase II clinical trial is designed to assess the safety and survival benefit of ipilimumab and pembrolizumab or durvalumab combination with or without chemodrug and/or bevacizumab as neoaduvant therapy on patients with NSCLC, including safety, pCR, mPR, PFS, ORR, DCR, and median survival time.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1: IT injection of double ICIs | Experimental | Drug: ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumabNeoadjuvant therapy: intra-tumor injection of double ICIs only. |
| Group 2: IT injection of double ICIs and chemodrug | Experimental | Drug: ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumabNeoadjuvant therapy: intra-tumor injection of double ICIs and chemodrug. |
| Group 3: IT injection of double ICIs and chemodrug plus bevacizumab | Experimental | Drug: ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumabNeoadjuvant therapy: intra-tumor injection of double ICIs and chemodrug plus bevacizumab. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Histologically or cytologically confirmed previously untreated non-small cell lung cancer. If a diagnostic biopsy is available, a pre-treatment biopsy is not required. Patients with a suspected lung cancer are eligible, but pathology must be confirmed prior to initiating treatment on study.
- Patients with stage IIIA must not have more than one mediastinal lymph node station involved by tumor.
- All patients must have lymph node evaluation of contralateral stations 2 and/or 4 to exclude N3 disease.
- The patient must be a suitable candidate for surgery, in the opinion of the treating physician.
- Signed and dated written informed consent must be provided by the patient prior to admission to the study in accordance with International Conference on Harmonization-Good Clinical Practice (ICH-GCP) guidelines and to the local legislation.
Key exclusion criteria (18 listed)
- Prior systemic therapy or radiation therapy for treatment of the current lung cancer.
- Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy) or investigational anti-cancer drug.
- Pregnant or lactating female.
- Unwillingness or inability to follow the procedures required in the protocol.
- Patients with pre-existing sensorineural hearing impairment/loss or newly diagnosed as documented by an audiology assessment performed prior to study enrollment may not be eligible for cisplatin and may be dispositioned to carboplatin, as determined by the treating physician.
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 |
|---|---|---|
| ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumabAlso: Other ICIsThis study has 3 subgroups: Arm 1. Ipilimumab +pembrolizumab or Ipilimumab +durvalumab is administrated with a total dose of 1-2mg/kg via intra-tumor fine needle injection in 10 min, every 3 weeks, total 3-4 times. Arm 2. Ipilimumab +pembrolizumab or Ipilimumab +durvalumab combined with idarubicin is administrated via intra-tumor fine needle injection in 15 min, every 3 weeks, total 3-4 times. Arm 3. Ipilimumab +pembrolizumab or Ipilimumab +durvalumab combined with idarubicin plus bevacizumab is administrated via intra-tumor fine needle injection in 20 min, every 3 weeks, total 3-4 times. | Drug | Group 1: IT injection of double ICIs, Group 2: IT injection of double ICIs and chemodrug, Group 3: IT injection of double ICIs and chemodrug plus bevacizumab |
Primary outcome
pCR rate for the study groups
Time frame: Six months
Pathologic complete response (pCR) is defined as after neoadjuvant therapy, the surgical specimen can not find any residual cancer cells.
mPR rate for the study groups
Time frame: Six months
Major pathologic response (MPR) is defined as pathological less than 10% survival cancer cells after tumor resection.
3 secondary outcomes
Toxicity of the study groups
Time frame: Six months
Response rates to neoadjuvant treatment
Time frame: Six years
Overall survival
Time frame: Six years
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 9 Jul 2024.
Related trials for 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
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
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
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.
Zhenfeng Zhang, MD, PhD principal investigator
Second Affiliated Hospital of Guangzhou Medical University
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 ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumab in people with Lung Cancer and Surgery, run by Second Affiliated Hospital of Guangzhou Medical University 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 7 inclusion and 18 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: looking for participants now, as of the sponsor's last update on 9 Jul 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 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?
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 Zhenfeng Zhang, MD, PhD (+862039195966, zhangzhf@gzhmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
pCR rate for the study groups (time frame: Six months). 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 9 Jul 2024.