Malignant Neoplasm of Nasopharynx TNM Staging Distant Metastasis (M)Phase 1NCT02915445
EpCAM CAR-T for Treatment of Advanced Solid Tumors
A Phase 1 study testing EpCAM CAR-T cells in people with Malignant Neoplasm of Nasopharynx TNM Staging Distant Metastasis (M) and Breast Cancer Recurrent, run by Sichuan University at 1 site in China.
Trial summary
This study is for patients that have nasopharyngeal carcinoma, breast cancer, gastric cancer and other solid tumors. As epithelial cell adhesion molecule (EpCAM) is a well characterized molecule that is closely with poor prognosis and tumor metastasis and invasion. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Malignant Neoplasm of Nasopharynx TNM Staging Distant Metastasis (M), Breast Cancer Recurrent, Gastric Cancer With Metastasis
- What is being tested?
- EpCAM CAR-T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- Jul 2016to Jul 2025
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Recurrent or refractory nasopharyngeal carcinoma and breast cancer and other solid tumors.
- Karnofsky score of greater than or equal to 60.
- Informed consent explained to, understood by and signed by subject/guardian. -
- Subject/guardian given copy of informed consent
- Treatment Inclusion criteria:
- Recurrent or refractory EpCAM-positive nasopharyngeal carcinoma, breast cancer, gastric cancer and other epithelial tumors determined by Immunohistochemistry (IHC) or RT-PCR. EpCAM expression in tumors on IHC should be greater than or equal to grade 2 and greater than or equal to 2+ intensity score. Wherein grades are defines as: Grade 0: no staining; Grade 1: 1-25%; Grade 2: 26-50% and Grade 3: 51-100% of cell staining for EpCAM and intensity scores are: negative; 1+; 2+ and 3+ using breast cancer standard arrays as a guide for intensity.
Show all 19Show fewer
- Age ≥ 18 years
- Life expectancy ≥ 6 weeks
- Karnofsky score ≥ 60
- Bilirubin less than or equal to 3x normal, AST less than or equal to 5x normal,
- ALT less than or equal to 5x, serum creatinine less than or equal to 2x upper limit of normal for age, and Hgb greater than or equal to 8.0
- Pulse oximetry of greater than or equal to 90% on room air.
- Sexually active subjects must be willing to utilize one of the more effective birth control methods for 6 months after the T cell infusion. The male partner should use a condom.
- Available autologous transduced T lymphocytes with greater than or equal to 20% expression of EpCAM CAR determined by flow-cytometry and killing of EpCAM-positive targets greater than or equal to 20% in cytotoxicity assay.
- Subjects should have been off other investigational antineoplastic therapy for two weeks prior to entry in this study.
- Cyclophosphamide will be allowed 72 hours preinfusion.
- Dexamethasone up to a total dose of 2 mg per day will be allowed if medically indicated.
- Informed consent explained to, understood by and signed by research subjects/guardian.
- Subject/guardian given copy of informed consent.
Who cannot join
- Known HIV positivity.
- Treatment Exclusion Criteria:
- Severe intercurrent infection.
- Known HIV positivity.
- Pregnant or lactating.
- History of hypersensitivity reactions to murine protein-containing products.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: T Cells Armed With Chimeric Antigen Receptor Recognizing EpCAM for Patients With Advanced Solid Tumors
This study is for patients that have nasopharyngeal carcinoma, breast cancer, gastric cancer and other solid tumors. As epithelial cell adhesion molecule (EpCAM) is a well characterized molecule that is closely with poor prognosis and tumor metastasis and invasion. Many therapies targeting EpCAM have shown benefits for cancer patients. This study is to determine the safety of the engineered T cells armed with chimeric antigen receptor (CAR-T) recognizing EpCAM. At the same time, efficacy is to be evaluated by the criteria of RECIST. The EpCAM CAR-T were produced by lentiviral transduction of the novel 2nd generation of CAR genes. Different cohorts of patients receive EpCAM CAR-T with a dose-escalating manner. This study is to find the largest dose of EpCAM CAR-T, to learn what the adverse effects are and to find out whether this experimental intervention might help patients with nasopharyngeal carcinoma, breast cancer and other EpCAM positive solid tumors.
Read the detailed description
In this study, the original tumor tissue specimen should be stained to determine the expression levels of EpCAM. Only the patients having tumor with high expression levels will be included.
50-100ml blood with be drawn to get enough CD3 T cells at least 2x10^7. After separation, PBMC will be activated via antibodies of CD3 and CD28 and then transduced by lentivirus bearing the EpCAM CAR gene. Then the EpCAM CAR-T cells will proliferate up to 10-100 folds for infusion. The produced cells will be frozen or infused if available.
Included patients will be preconditioned by cyclophosphamide for lymphodepletion if the levels of white blood cells and lymphocytes are normal. Infusion of T cells, at least 1 day after lymphodepletion, is dose escalating and beginning at the lowest level. If the first level is proven to be safe, the next level will be proceeded. Once severe side effects were observed, the dose will be lowered or the dose will be stopped.
During infusion, patients will be taken care of by cardiogram monitor. Blood drawing will be taken before infusion, at 4h after infusion and on day 4, 7, 14, 30, 60, 90, 120, 150, 180 to determine the presence of CAR-T cells. At the same time, cytokines including IL-6, TNF-alpha and IFN-gamma and C-reactive protein levels will be determined. Routine imaging studies will be proceeded.
To see whether there are long-term side effects of this therapy, patients received CAR-T cells will be followed up to at least 15 years.
- Conditions
- Malignant Neoplasm of Nasopharynx TNM Staging Distant Metastasis (M), Breast Cancer Recurrent, Gastric Cancer With Metastasis
- Being tested
- EpCAM CAR-T cells
- Keywords
- EpCAM CAR-T, solid tumors, cancer immunotherapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EpCAM CAR-T cellsBiological
Patients included will be infused the autologous T cells armed with CAR recognizing EpCAM. After infusion, cytokines and other medical test will be performed.
| Study group | Role | What they receive |
|---|---|---|
| EpCAM CAR-T cells | Experimental | Autologous T cells from patient are engineered to expressing a special chimeric antigen receptor to recognizing EpCAM by lentiviral vector. The engineered T cells were then endowed cytotoxicity to the tumor cells and hold the potential to inhibit the advance of tumors. Receives: Biological: EpCAM CAR-T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with treatment-related adverse events/dose limiting toxicity as assessed by CTCAE v4.0
Determine the largest dose of EpCAM CAR-T cells for patients with nasopharyngeal carcinoma, breast cancer and other tumors expressing EpCAM.
Measured: 6 weeks after infusion
Secondary outcomes (2)
Response rate of participants treated with EpCAM CAR-T cells assessed by RECIST v1.1
Determine whether there is therapeutic efficacies of the safe dose infusion of EpCAM CAR-T cells for patients with solid tumors.
Measured: 24 months after infusion of the CAR-T cells
Persistence of EpCAM CAR-T cells and correlation with the Response rate
Measured: 24 months post CAR-T infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2016 (estimated)
- Study startJul 2016
- Primary completionJul 2025 (estimated)
- Study completionJul 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Malignant Neoplasm of Nasopharynx TNM Staging Distant Metastasis (M)Studies of the same condition, open and under way.
- More trials run by Sichuan 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sichuan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wei Wang, Sichuan University
- Investigators
- Wei Wang, Ph.D, Principal investigator, State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02915445
- Sponsor's protocol ID
- SKLB-083
- Status last verified
- Nov 2023
- First submitted
- 21 Sep 2016
- Last updated
- 22 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Osta WA, Chen Y, Mikhitarian K, Mitas M, Salem M, Hannun YA, Cole DJ, Gillanders WE. EpCAM is overexpressed in breast cancer and is a potential target for breast cancer gene therapy. Cancer Res. 2004 Aug 15;64(16):5818-24. doi: 10.1158/0008-5472.CAN-04-0754.
PubMed 15313925Burges A, Wimberger P, Kumper C, Gorbounova V, Sommer H, Schmalfeldt B, Pfisterer J, Lichinitser M, Makhson A, Moiseyenko V, Lahr A, Schulze E, Jager M, Strohlein MA, Heiss MM, Gottwald T, Lindhofer H, Kimmig R. Effective relief of malignant ascites in patients with advanced ovarian cancer by a trifunctional anti-EpCAM x anti-CD3 antibody: a phase I/II study. Clin Cancer Res. 2007 Jul 1;13(13):3899-905. doi: 10.1158/1078-0432.CCR-06-2769.
PubMed 17606723Stoecklein NH, Siegmund A, Scheunemann P, Luebke AM, Erbersdobler A, Verde PE, Eisenberger CF, Peiper M, Rehders A, Esch JS, Knoefel WT, Hosch SB. Ep-CAM expression in squamous cell carcinoma of the esophagus: a potential therapeutic target and prognostic marker. BMC Cancer. 2006 Jun 23;6:165. doi: 10.1186/1471-2407-6-165.
PubMed 16796747Spizzo G, Went P, Dirnhofer S, Obrist P, Moch H, Baeuerle PA, Mueller-Holzner E, Marth C, Gastl G, Zeimet AG. Overexpression of epithelial cell adhesion molecule (Ep-CAM) is an independent prognostic marker for reduced survival of patients with epithelial ovarian cancer. Gynecol Oncol. 2006 Nov;103(2):483-8. doi: 10.1016/j.ygyno.2006.03.035. Epub 2006 May 6.
PubMed 16678891Murakami N, Mori T, Yoshimoto S, Ito Y, Kobayashi K, Ken H, Kitaguchi M, Sekii S, Takahashi K, Yoshio K, Inaba K, Morota M, Sumi M, Itami J. Expression of EpCAM and prognosis in early-stage glottic cancer treated by radiotherapy. Laryngoscope. 2014 Nov;124(11):E431-6. doi: 10.1002/lary.24839. Epub 2014 Jul 14.
PubMed 25043563Deng Z, Wu Y, Ma W, Zhang S, Zhang YQ. Adoptive T-cell therapy of prostate cancer targeting the cancer stem cell antigen EpCAM. BMC Immunol. 2015 Jan 31;16(1):1. doi: 10.1186/s12865-014-0064-x.
PubMed 25636521Sarkar T, Sarkar T, Goswami M, Robaszkiewicz A, Sarkar K. Integrated transcriptome analysis and in silico investigations identify KHDRBS3 to target with steroidal lactone in paclitaxel resistance breast cancer. Biochem Biophys Res Commun. 2025 Sep 1;777:152332. doi: 10.1016/j.bbrc.2025.152332. Epub 2025 Jul 10.
PubMed 40651363
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- T Cells Armed With Chimeric Antigen Receptor Recognizing EpCAM for Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT02915445
- Acronym / sponsor ID
- SKLB-083
- Conditions
- Malignant Neoplasm of Nasopharynx TNM Staging Distant Metastasis (M), Breast Cancer Recurrent, Gastric Cancer With Metastasis
- Keywords
- EpCAM CAR-T, solid tumors, cancer immunotherapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Sichuan UniversityUniversity, hospital or other
- Study start
- Jul 2016
- Primary completion
- Jul 2025 (estimated)
- Study completion
- Jul 2025 (estimated)
- First posted
- 27 Sep 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.
This study is for patients that have nasopharyngeal carcinoma, breast cancer, gastric cancer and other solid tumors. As epithelial cell adhesion molecule (EpCAM) is a well characterized molecule that is closely with poor prognosis and tumor metastasis and invasion. Many therapies targeting EpCAM have shown benefits for cancer patients. This study is to determine the safety of the engineered T cells armed with chimeric antigen receptor (CAR-T) recognizing EpCAM. At the same time, efficacy is to be evaluated by the criteria of RECIST. The EpCAM CAR-T were produced by lentiviral transduction of the novel 2nd generation of CAR genes. Different cohorts of patients receive EpCAM CAR-T with a dose-escalating manner. This study is to find the largest dose of EpCAM CAR-T, to learn what the adverse effects are and to find out whether this experimental intervention might help patients with nasopharyngeal carcinoma, breast cancer and other EpCAM positive solid tumors.
Detailed description
In this study, the original tumor tissue specimen should be stained to determine the expression levels of EpCAM. Only the patients having tumor with high expression levels will be included.
50-100ml blood with be drawn to get enough CD3 T cells at least 2x10^7. After separation, PBMC will be activated via antibodies of CD3 and CD28 and then transduced by lentivirus bearing the EpCAM CAR gene. Then the EpCAM CAR-T cells will proliferate up to 10-100 folds for infusion. The produced cells will be frozen or infused if available.
Included patients will be preconditioned by cyclophosphamide for lymphodepletion if the levels of white blood cells and lymphocytes are normal. Infusion of T cells, at least 1 day after lymphodepletion, is dose escalating and beginning at the lowest level. If the first level is proven to be safe, the next level will be proceeded. Once severe side effects were observed, the dose will be lowered or the dose will be stopped.
During infusion, patients will be taken care of by cardiogram monitor. Blood drawing will be taken before infusion, at 4h after infusion and on day 4, 7, 14, 30, 60, 90, 120, 150, 180 to determine the presence of CAR-T cells. At the same time, cytokines including IL-6, TNF-alpha and IFN-gamma and C-reactive protein levels will be determined. Routine imaging studies will be proceeded.
To see whether there are long-term side effects of this therapy, patients received CAR-T cells will be followed up to at least 15 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| EpCAM CAR-T cells | Experimental | Biological: EpCAM CAR-T cellsAutologous T cells from patient are engineered to expressing a special chimeric antigen receptor to recognizing EpCAM by lentiviral vector. The engineered T cells were then endowed cytotoxicity to the tumor cells and hold the potential to inhibit the advance of tumors. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Recurrent or refractory nasopharyngeal carcinoma and breast cancer and other solid tumors.
- Karnofsky score of greater than or equal to 60.
- Informed consent explained to, understood by and signed by subject/guardian. -
- Subject/guardian given copy of informed consent
- Recurrent or refractory EpCAM-positive nasopharyngeal carcinoma, breast cancer, gastric cancer and other epithelial tumors determined by Immunohistochemistry (IHC) or RT-PCR. EpCAM expression in tumors on IHC should be greater than or equal to grade 2 and greater than or equal to 2+ intensity score. Wherein grades are defines as: Grade 0: no staining; Grade 1: 1-25%; Grade 2: 26-50% and Grade 3: 51-100% of cell staining for EpCAM and intensity scores are: negative; 1+; 2+ and 3+ using breast cancer standard arrays as a guide for intensity.
Key exclusion criteria (6 listed)
- Known HIV positivity.
- Severe intercurrent infection.
- Known HIV positivity.
- Pregnant or lactating.
- History of hypersensitivity reactions to murine protein-containing products.
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 |
|---|---|---|
| EpCAM CAR-T cellsPatients included will be infused the autologous T cells armed with CAR recognizing EpCAM. After infusion, cytokines and other medical test will be performed. | Biological | EpCAM CAR-T cells |
Primary outcome
Number of participants with treatment-related adverse events/dose limiting toxicity as assessed by CTCAE v4.0
Time frame: 6 weeks after infusion
Determine the largest dose of EpCAM CAR-T cells for patients with nasopharyngeal carcinoma, breast cancer and other tumors expressing EpCAM.
2 secondary outcomes
Response rate of participants treated with EpCAM CAR-T cells assessed by RECIST v1.1
Time frame: 24 months after infusion of the CAR-T cells
Persistence of EpCAM CAR-T cells and correlation with the Response rate
Time frame: 24 months post CAR-T infusion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2023.
- Background: PubMed 15313925Osta WA, Chen Y, Mikhitarian K, Mitas M, Salem M, Hannun YA, Cole DJ, Gillanders WE. EpCAM is overexpressed in breast cancer and is a potential target for breast cancer gene therapy. Cancer Res. 2004 Aug 15;64(16):5818-24. doi: 10.1158/0008-5472.CAN-04-0754.
- Background: PubMed 17606723Burges A, Wimberger P, Kumper C, Gorbounova V, Sommer H, Schmalfeldt B, Pfisterer J, Lichinitser M, Makhson A, Moiseyenko V, Lahr A, Schulze E, Jager M, Strohlein MA, Heiss MM, Gottwald T, Lindhofer H, Kimmig R. Effective relief of malignant ascites in patients with advanced ovarian cancer by a trifunctional anti-EpCAM x anti-CD3 antibody: a phase I/II study. Clin Cancer Res. 2007 Jul 1;13(13):3899-905. doi: 10.1158/1078-0432.CCR-06-2769.
- Background: PubMed 16796747Stoecklein NH, Siegmund A, Scheunemann P, Luebke AM, Erbersdobler A, Verde PE, Eisenberger CF, Peiper M, Rehders A, Esch JS, Knoefel WT, Hosch SB. Ep-CAM expression in squamous cell carcinoma of the esophagus: a potential therapeutic target and prognostic marker. BMC Cancer. 2006 Jun 23;6:165. doi: 10.1186/1471-2407-6-165.
- Background: PubMed 16678891Spizzo G, Went P, Dirnhofer S, Obrist P, Moch H, Baeuerle PA, Mueller-Holzner E, Marth C, Gastl G, Zeimet AG. Overexpression of epithelial cell adhesion molecule (Ep-CAM) is an independent prognostic marker for reduced survival of patients with epithelial ovarian cancer. Gynecol Oncol. 2006 Nov;103(2):483-8. doi: 10.1016/j.ygyno.2006.03.035. Epub 2006 May 6.
- Background: PubMed 25043563Murakami N, Mori T, Yoshimoto S, Ito Y, Kobayashi K, Ken H, Kitaguchi M, Sekii S, Takahashi K, Yoshio K, Inaba K, Morota M, Sumi M, Itami J. Expression of EpCAM and prognosis in early-stage glottic cancer treated by radiotherapy. Laryngoscope. 2014 Nov;124(11):E431-6. doi: 10.1002/lary.24839. Epub 2014 Jul 14.
- Background: PubMed 25636521Deng Z, Wu Y, Ma W, Zhang S, Zhang YQ. Adoptive T-cell therapy of prostate cancer targeting the cancer stem cell antigen EpCAM. BMC Immunol. 2015 Jan 31;16(1):1. doi: 10.1186/s12865-014-0064-x.
- Derived from this study: PubMed 40651363Sarkar T, Sarkar T, Goswami M, Robaszkiewicz A, Sarkar K. Integrated transcriptome analysis and in silico investigations identify KHDRBS3 to target with steroidal lactone in paclitaxel resistance breast cancer. Biochem Biophys Res Commun. 2025 Sep 1;777:152332. doi: 10.1016/j.bbrc.2025.152332. Epub 2025 Jul 10.
- Individual participant dataSharing planned: No
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.
Wei Wang, Ph.D principal investigator
State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan 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 EpCAM CAR-T cells in people with Malignant Neoplasm of Nasopharynx TNM Staging Distant Metastasis (M) and Breast Cancer Recurrent, run by Sichuan 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 19 inclusion and 6 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 22 Nov 2023. 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with treatment-related adverse events/dose limiting toxicity as assessed by CTCAE v4.0 (time frame: 6 weeks after infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02915445, which also lists 7 linked publications.
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 22 Nov 2023.