Lung Squamous Cell CarcinomaPhase 1NCT02876978
Anti-GPC3 CAR T for Recurrent or Refractory Lung Squamous Cell Carcinoma
A Phase 1 study testing CAR-GPC3 T Cells, Fludarabine and Cyclophosphamide in people with Lung Squamous Cell Carcinoma, run by CARsgen Therapeutics Co., Ltd. at 1 site in China.
Trial summary
The purpose of this study is to observe and confirm the safety, tolerance and cell pharmacokinetics of lentivirus-transduced CAR-GPC3 T cells (CAR-GPC3 T cells targeting GPC3) Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Lung Squamous Cell Carcinoma
- What is being tested?
- CAR-GPC3 T Cells, Fludarabine and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- Mar 2016to Apr 2019
- Phase
- Phase 1
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men or women aged 18~70 years old
- Subjects are diagnosed as refractory, recurrent ,metastatic, advanced lung squamous cell carcinoma by histological and cytological methods including specific lesion-targeted brush biopsy, lavage and fine needle aspiration;
- Have at least one new measurable tumor lesion compared with previous irradiated region
- Tumor tissues samples confirmed as GPC3-positive
- Expected survival≥12 weeks
- ECOG scored as 0-1 or KPS grading > 80
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- ANC≥1500/nm3
- PLT≥100000/mm3
- Hb≥9.0g/dL
- Serum creatinine≤2.5mg/dL，CCR≥50ml/min (renal malfunction defined as CCR<50ml/min according to Cockroft-Gault formula)
- ALT and AST≤2.5ULN; for liver metastasis，ALT and AST ≤5ULN
- Serum TBiL≤3.0mg/dL, TBiL≤2.5ULN
- PT: INR < 1.7 or extended PT to normal value < 4s
- Adequate venous access for apheresis or venous blood collection, and no other contraindication of blood cell separation
- Patients with willingness to be in this study and able to provide informed consent
- Capable of receiving treatment and follow up, included subjects are required to receive treatment in the enrolled centre
- Women of childbearing age are required to take acceptable measures to minimize the possibility of pregnancy during whole session. Women of childbearing age must have negative results of serum or urine tests within 24 hours prior to infusion. Women subjects must not be in lactation;
Who cannot join
- CAR-T positive rate < 10%
- pregnant women or women in lactation
- active HBV or HCV infection
- HIV/AIDS infection
- active infection
- previously suffered from diseases or concurrent diseases as followed：
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- patients confirmed as severe autoimmune diseases in long-term (over 2 months) need of systemic immune inhibitors (steroid) or as immune-mediated symptomatic diseases including ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus (SLE), autoimmune vasculitis (for example, Wegener's granulomatosis)
- subjects with previous diagnosis as motor neurone disease caused by autoimmunity
- subjects previously suffered from toxic epidermal necrolysis (TEN)
- subjects with any mental diseases including dementia, mental status change that may impinge the understanding and performance of informed consent and related questionnaire
- subjects with severe, uncontrollable diseases judged by investigators that may hinder them receiving this treatment
- subjects with previously active malignant tumors including basal or squamous skin cancer, superficial bladder cancer, and in situ breast carcinoma within 5 years who had been completely cured without the need of follow-up treatment are not excluded.
- during ongoing treatment using systemic steroid or steroid inhalants
- previous treatment used gene therapy products
- previous experience of immunotherapies including CIK, DC, DC-CIK, LAK for the treatment of cancer
- allergic to immunotherapies or related drugs
- patients in need of treatment for heart disease with ≥2 NYHA or for poor controlled hypertension
- subjects with unstable or active peptic ulcer or alimentary tract hemorrhage
- subjects with previous organ transplantation or ready for organ transplantation
- subjects in need of anticoagulant therapy treatment (warfarin or heparin)
- subjects judged by investigators as not appropriate for this study
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Shanghai Chest Hospital,Shanghai Jiaotong University
Shanghai, Shanghai Municipality, 200030
About this study
Official title: Preliminary Clinical Study of Autologous T Cells Modified Chimeric Antigen Receptor (CAR) Targeting GPC3 for the Treatment of Recurrent or Refractory Lung Squamous Cell Carcinoma
The purpose of this study is to observe and confirm the safety, tolerance and cell pharmacokinetics of lentivirus-transduced CAR-GPC3 T cells (CAR-GPC3 T cells targeting GPC3)
Read the detailed description
A single-center, open-label pilot study to determine the safety, tolerance and engraftment potential of CAR-GPC3 T cells in subjects with GPC3+ positive lung squamous cell carcinoma.
Primary objectives:
Observe and determine the safety and tolerance in escalating dose infusion of CAR-GPC3 T cells (CAR T cells targeting GPC3) transduced with the lentiviral vector, and the survival of the CAT-GPC3 T cells in vivo, referred to as engraftment potential.
Secondary objectives:
The following indexes are monitored for curative effect of CAR-GPC3 T cells on lung squamous cell carcinoma:
- Objective response rate (ORR), is defined as the ratio of patients diagnosed as partial remission (PR) to complete remission (CR) according to RECIST 1.1 criteria.
- Progression free survival (PFS), is defined as the duration from baseline to PD (audited and confirmed by independent imaging), or to the day of any death event. The earlier one shall prevail.
- Time to tumor progression (TTP), is defined as the duration from baseline to disease starts to get worse or spreads to other parts of the body.
- Overall survival (OS), is defined as the time period from the 1st day of treatment to the day of death for any reason. For patients who are still alive at the data analysis day, OS data is subject to the last confirmed time of survival patients.
- Conditions
- Lung Squamous Cell Carcinoma
- Being tested
- CAR-GPC3 T Cells, Fludarabine, Cyclophosphamide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CAR-GPC3 T CellsGenetic
Also called Anti-GPC3 CAR T, CAR T cells redirected to Glypican-3
Intravenous infusion of CAR-GPC3 T cells is conducted 1 - 2 days following lymphodepletion.
FludarabineDrug
30 mg/m^2/day x 4 days
CyclophosphamideDrug
500 mg/m^2/day x 2 days
| Study group | Role | What they receive |
|---|---|---|
| CAR-GPC3 T cells | Experimental | Intravenous infusion with escalating dose is adopted in this study.
Total dosage: 1 x 10^5 - 2 x 10^9 CAR-GPC3 T cells/kg
The next dose and interval depends on the response of the subject to previous dose.
Lymphodepletion:
Fludarabine: 30 mg/m^2/day x 4 days; Cyclophosphamide: 500 mg/m^2/day x 2 days. Adjustment is in discretion of the investigator based on individual response. Receives: Genetic: CAR-GPC3 T Cells; Drug: Fludarabine; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerance: Occurrence of study related adverse events
Occurrence of study related adverse events, defined as laboratory toxicities and clinical events that are possibly, likely or definitely related to study treatment at any time from the infusion until week 24. This will include infusive toxicity, and any toxicity possibly related to the CAR-GPC3 T cells.
Measured: 24 weeks
Secondary outcomes (1)
Engraftment: the DNA vector copies per mL blood of CAR-GPC3 T cells
The DNA vector copies per mL blood of CAR-GPC3 T cells on week 4 after the first infusion by Q-PCR. Q-PCR for CAR-GPC3 vector sequences will also be performed after infusion thereafter until any 2 sequential tests are negative documenting loss of CAR-GPC3 T cells within 2 years.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2016 (estimated)
- Study startMar 2016
- Primary completionOct 2017 (estimated)
- Study completionApr 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung Squamous Cell 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- CARsgen Therapeutics Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jiang Liyan, MD, Principal investigator, Shanghai Chest Hospital,Shanghai Jiaotong University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02876978
- Sponsor's protocol ID
- CG1003
- Status last verified
- Aug 2016
- First submitted
- 9 Aug 2016
- Last updated
- 24 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preliminary Clinical Study of Autologous T Cells Modified Chimeric Antigen Receptor (CAR) Targeting GPC3 for the Treatment of Recurrent or Refractory Lung Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT02876978
- Acronym / sponsor ID
- CG1003
- Conditions
- Lung Squamous Cell Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- CARsgen Therapeutics Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- Mar 2016
- Primary completion
- Oct 2017 (estimated)
- Study completion
- Apr 2019 (estimated)
- First posted
- 24 Aug 2016 (estimated)
- 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 purpose of this study is to observe and confirm the safety, tolerance and cell pharmacokinetics of lentivirus-transduced CAR-GPC3 T cells (CAR-GPC3 T cells targeting GPC3)
Detailed description
A single-center, open-label pilot study to determine the safety, tolerance and engraftment potential of CAR-GPC3 T cells in subjects with GPC3+ positive lung squamous cell carcinoma.
Primary objectives:
Observe and determine the safety and tolerance in escalating dose infusion of CAR-GPC3 T cells (CAR T cells targeting GPC3) transduced with the lentiviral vector, and the survival of the CAT-GPC3 T cells in vivo, referred to as engraftment potential.
Secondary objectives:
The following indexes are monitored for curative effect of CAR-GPC3 T cells on lung squamous cell carcinoma:
- Objective response rate (ORR), is defined as the ratio of patients diagnosed as partial remission (PR) to complete remission (CR) according to RECIST 1.1 criteria.
- Progression free survival (PFS), is defined as the duration from baseline to PD (audited and confirmed by independent imaging), or to the day of any death event. The earlier one shall prevail.
- Time to tumor progression (TTP), is defined as the duration from baseline to disease starts to get worse or spreads to other parts of the body.
- Overall survival (OS), is defined as the time period from the 1st day of treatment to the day of death for any reason. For patients who are still alive at the data analysis day, OS data is subject to the last confirmed time of survival patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CAR-GPC3 T cells | Experimental | Genetic: CAR-GPC3 T Cells, Drug: Fludarabine, Drug: CyclophosphamideIntravenous infusion with escalating dose is adopted in this study. Total dosage: 1 x 10^5 - 2 x 10^9 CAR-GPC3 T cells/kg The next dose and interval depends on the response of the subject to previous dose. Lymphodepletion: Fludarabine: 30 mg/m^2/day x 4 days; Cyclophosphamide: 500 mg/m^2/day x 2 days. Adjustment is in discretion of the investigator based on individual response. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Men or women aged 18~70 years old
- Subjects are diagnosed as refractory, recurrent ,metastatic, advanced lung squamous cell carcinoma by histological and cytological methods including specific lesion-targeted brush biopsy, lavage and fine needle aspiration;
- Have at least one new measurable tumor lesion compared with previous irradiated region
- Tumor tissues samples confirmed as GPC3-positive
- Expected survival≥12 weeks
Key exclusion criteria (21 listed)
- CAR-T positive rate < 10%
- pregnant women or women in lactation
- active HBV or HCV infection
- HIV/AIDS infection
- active infection
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 |
|---|---|---|
| CAR-GPC3 T CellsAlso: Anti-GPC3 CAR T, CAR T cells redirected to Glypican-3Intravenous infusion of CAR-GPC3 T cells is conducted 1 - 2 days following lymphodepletion. | Genetic | CAR-GPC3 T cells |
| Fludarabine30 mg/m^2/day x 4 days | Drug | CAR-GPC3 T cells |
| Cyclophosphamide500 mg/m^2/day x 2 days | Drug | CAR-GPC3 T cells |
Primary outcome
Safety and tolerance: Occurrence of study related adverse events
Time frame: 24 weeks
Occurrence of study related adverse events, defined as laboratory toxicities and clinical events that are possibly, likely or definitely related to study treatment at any time from the infusion until week 24. This will include infusive toxicity, and any toxicity possibly related to the CAR-GPC3 T cells.
1 secondary outcome
Engraftment: the DNA vector copies per mL blood of CAR-GPC3 T cells
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2016.
- 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.
Jiang Liyan, MD principal investigator
Shanghai Chest Hospital,Shanghai Jiaotong University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CAR-GPC3 T Cells, Fludarabine and Cyclophosphamide in people with Lung Squamous Cell Carcinoma, run by CARsgen Therapeutics Co., Ltd. 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 17 inclusion and 21 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 24 Aug 2016. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 Li Zonghai, MD (86-21-54489926 ext. 817, zonghaili@carsgen.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerance: Occurrence of study related adverse events (time frame: 24 weeks). 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 24 Aug 2016.