Malignant Tumor of Pancreas Metastatic to LiverPhase 2/3NCT04037241
Study of Anti-CEA CAR-T + Chemotherapy VS Chemotherapy Alone in Patients With CEA+Pancreatic Cancer & Liver Metastases
A Phase 2/3 study testing Anti-CEA CAR-T cells, gemcitabine/nab paclitaxel and NLIR+FU/FA in people with Malignant Tumor of Pancreas Metastatic to Liver, run by Sorrento Therapeutics, Inc..
Trial summary
This study is a randomized open-label phase 2b study of the efficacy and safety of regional infusion therapy with Anti-CEA CAR-T cells using the hepatic immunotherapy for metastases (HITM) method and the Trisalus pressure enabling drug delivery (PEDD) device alternating with systemic chemotherapy versus chemotherapy… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Tumor of Pancreas Metastatic to Liver
- What is being tested?
- Anti-CEA CAR-T cells, gemcitabine/nab paclitaxel and NLIR+FU/FA
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Nov 2021to 1 Jan 2022
- Phase
- Phase 2/3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have documented CEA-expressing pancreatic adenocarcinoma with unresectable liver metastases. Documentation of CEA-expressing adenocarcinoma may be demonstrated by an elevated serum CEA level (≥ 10 ng/mL) or by the detection of CEA on the cell surface of adenocarcino3.
- Documentation of disease progression of pancreatic adenocarcinoma following the initiation of first-line treatment with FOLFIRINOX or gemcitabine-based therapy.ma cells by immunohistochemistry (IHC).
- The primary pancreatic tumor may be intact and limited lung metastases (≤ 3 lesions, none > 1 cm in longest diameter) and lymphoid metastases (≤ 3 lesions, none > 1 cm in longest diameter) are permitted.
- There must be at least one measurable metastatic liver lesion ( ≥ 10 mm in longest diameter).
- ECOG performance status of 0 or 1.
- Be willing and able to comply with the study schedule and all other protocol requirements.
- Females of childbearing potential must have 2 negative pregnancy tests prior to the start of study treatment, and must agree to pregnancy tests during the study; sexually active female and male patients must be willing to use an effective birth control to avoid pregnancy.
Who cannot join
- Received anti-cancer chemotherapy or investigational systemic anti-cancer treatments other than first line FOLFIRINOX or gemcitabine-based chemotherapy for advanced pancreatic adenocarcinoma.
- Received FOLFIRINOX or gemcitabine-based therapy within 14 days before receiving the first dose of study treatment.
- Have any unresolved toxicity > Grade 1 from previous anticancer therapy, except for stable chronic toxicities (≤ Grade 2) that are not expected to resolve.
- Have a history of histologically confirmed metastases outside the liver, lungs, or lymph nodes.
- More than 50% replacement of one or both hepatic lobes with tumor.
- Tumor causing biliary obstruction not amenable to stenting.
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- Received prior anti-CEA agents, CAR-T, CAR-T cell line, CAR-NK, CAR-pNK, or CAR-NK cell line therapies.
- Have any clinically significant low baseline lab results for hemoglobin, platelet counts, or neutrophil counts at screening.
- Has any untreated or ongoing intra-abdominal infection or bowel obstruction.
- Has any clinically significant elevated baseline lab results for serum creatinine, aspartate aminotransferase (AST), and total bilirubin (except for patients in whom hyperbilirubinemia is attributed to Gilbert's syndrome), and alkaline phosphatase at screening.
- Known HIV or acquired immunodeficiency syndrome-related illness, acute or history of chronic hepatitis B or C.
- Female patients who are pregnant or breastfeeding.
- Has active bacterial, viral or fungal infections.
- Has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from participating in the study.
- Has any condition, including the presence of laboratory abnormalities that places the patient at an unacceptable risk if the patient was to participate in the study.
- Are receiving medications that are strong inducers CYP3A4 or CYP2C8 within 2 weeks of initiating treatment in the Bridging Therapy Period (rifampicin, carbamazepine, phenytoin, efavirenz, nevirapine, rifabutin, rifapentine, St. John's wort).
- Are receiving medications that inhibit CYP3A4 or CYP2C8 within 1 week of initiating treatment in the Bridging Therapy Period (ketoconazole and other imidazole antifungals, erythromycin, clarithromycin, itraconazole, voriconazole, fluoxetine, gemfibrozil, cimetidine, lopinavir, nefazodone, telaprevir, ritonavir, saquinavir, indinavir, or nelfinavir).
- Are receiving medications that inhibit UGT1A1 within 1 week of initiating nanoliposomal irinotecan therapy (atazanavir, gemfibrozil, indinavir).
- Left ventricular ejection fraction (LVEF) < 40%
About this study
Official title: A Randomized Open-Label Phase 2b Study of Hepatic Infusions of Anti-CEA CAR-T Cells Alternating With Systemic Chemotherapy Versus Chemotherapy Alone In Patients With Liver Metastases Due To CEA-Expressing Pancreatic Adenocarcinoma
This study is a randomized open-label phase 2b study of the efficacy and safety of regional infusion therapy with Anti-CEA CAR-T cells using the hepatic immunotherapy for metastases (HITM) method and the Trisalus pressure enabling drug delivery (PEDD) device alternating with systemic chemotherapy versus chemotherapy alone in patients with CEA-expressing pancreatic adenocarcinoma with liver metastases.
Read the detailed description
The study consists of 5 periods: Screening/Leukapheresis Period, Bridging Therapy Period, Randomization Period, Treatment Period, and Observation Period (which will be the long-term follow-up period to monitor for overall survival and long-term safety).
Patients in this trial with CEA-expressing pancreatic adenocarcinoma with liver metastases must have developed disease progression after first-line treatment with FOLFIRINOX (irinotecan, 5-fluorouracil, leucovorin, and oxaliplatin) or gemcitabine-based chemotherapy. Patients will be randomized to either the "anti-CEA CAR-T Cells + systemic chemotherapy treatment arms", or the "chemotherapy alone treatment arms."
If the patients achieve at least stable disease during the Bridging Therapy Period, they will be in the Second-Line Group of Treatment Arms. Patients who develop disease progression during the Bridging Period will be in the Third-Line Group of Treatment Arms.
Patients in the Second-Line or Third-Line treatment arms who are randomized to the treatment arms of "Anti-CEA CAR-T cells plus systemic chemotherapy" will receive hepatic infusions of Anti-CEA CAR-T cells in Cycles 1 and 3 (ie, each 42-day cycle is 3 weekly doses of Anti-CEA CAR-T cells administered as hepatic arterial infusions using a PEDD device with low dose systemic IL-2 support), alternating with the systemic chemotherapy regimen they received during the Bridging Therapy Period in Cycle 2 and Cycles >= 4. Systemic chemotherapy will be administered in 28-day cycles until the development of disease progression.
Patients in the Second-Line or Third-Line treatment arms who are randomized to the treatment arms "chemotherapy alone" arms will continue to receive the same systemic chemotherapy that they received during the Bridging Therapy Period. Systemic chemotherapy will be administered in 28-day or 21-day cycles (depending on the type of systemic chemotherapy regimen the patient will receive) until the development of disease progression.
- Being tested
- Anti-CEA CAR-T cells, gemcitabine/nab paclitaxel, NLIR+FU/FA, Capecitabine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-CEA CAR-T cellsBiological
Also called SureFire Precision Infusion System, K171355, TriSalus PEDD
Doses will be delivered by hepatic arterial infusions using a pressure enabled drug delivery (PEDD) device
gemcitabine/nab paclitaxelDrug
Also called Gemzar, Abraxane
systemic chemotherapy regimen
NLIR+FU/FADrug
Also called Onivyde, Adrucil, Leucovorin
systemic chemotherapy regimen
CapecitabineDrug
Also called Xeloda
systemic chemotherapy regimen
| Study group | Role | What they receive |
|---|---|---|
| 2nd Line: Anti-CEA CAR-T Cells + gemcitabine/nab paclitaxel | Experimental | Patients in the "anti-CEA CAR-T Cells plus gemcitabine/nab paclitaxel arm" will have achieved at least stable disease during the Bridging Therapy Period with gemcitabine/nab paclitaxel, and will receive the CAR-T cells in Cycles 1 and 3 and the gemcitabine/nab paclitaxel regimen they received during the Bridging Therapy Period in Cycle 2 and Cycles ≥ 4 of the Treatment Period. Treatment will continue until the development of disease progression. Receives: Biological: Anti-CEA CAR-T cells; Drug: gemcitabine/nab paclitaxel |
| 2nd Line: Anti-CEA CAR-T Cells Plus NLIR+FU/FA | Experimental | Patients in the "anti-CEA CAR-T Cells plus and nanolipsomal irinotecan (NLIR) + Fluorouracil/folinic acid (FU/FA)" will have achieved at least stable disease during the Bridging Therapy Period with NLIR + FU/FA, and will receive the CAR-T cells in Cycles 1 and 3 and the NLIR/FU/FA regimen they received during the Bridging Therapy Period in Cycle 2 and Cycles ≥ 4 of the Treatment Period. Treatment will continue until the development of disease progression. Receives: Biological: Anti-CEA CAR-T cells; Drug: NLIR+FU/FA |
| 2nd Line: Gemcitabine /nab paclitaxel Alone | Active comparator | Patients in the chemotherapy alone treatment arm who achieved at least stable disease during the Bridging Therapy Period while receiving gemcitabine plus nab paclitaxel will continue treatment with the chemotherapy regimen they received during the Treatment Period. This regimen will be administered in 28-day cycles until the development of disease progression. Receives: Drug: gemcitabine/nab paclitaxel |
| 2nd Line: NLIR + FU/FA Alone | Active comparator | Patients in the chemotherapy alone treatment arm who achieved at least stable disease during the Bridging Therapy Period while receiving nanoliposomal irinotecan (NLIR) + Fluorouracil/folinic acid (FU/FA) will continue treatment with the chemotherapy regimen they received during the Treatment Period. This regimen will be administered in 28-day cycles until the development of disease progression. Receives: Drug: NLIR+FU/FA |
| 3rd Line: Anti-CEA CAR-T Cells Plus NLIR+FU/FA | Experimental | Patients randomized to the anti-CEA CAR-T Cells plus chemotherapy treatment arm who developed disease progression during the Bridging Therapy Period will receive the CAR-T cells in Cycles 1 and 3. Nanoliposomal irinotecan plus fluorouracil/leucovorin chemotherapy will be administered in Cycle 2 and Cycles ≥ 4 of the Treatment Period to patients who progressed on nab paclitaxel plus gemcitabine during the Bridging Therapy Period. Treatment will continue until the development of disease progression. Receives: Biological: Anti-CEA CAR-T cells; Drug: NLIR+FU/FA |
| 3rd Line: Anti-CEA CAR-T Cells Plus Capecitabine | Experimental | Patients randomized to the anti-CEA CAR-T Cells plus chemotherapy treatment arm who developed disease progression during the Bridging Therapy Period will receive the CAR-T cells in Cycles 1 and 3. Capecitabine chemotherapy will be administered in Cycle 2 and Cycles ≥ 4 of the Treatment Period to patients who progressed on nanoliposomal irinotecan fluorouracil/leucovorin during the Bridging Therapy Period. Treatment will continue until the development of disease progression. Receives: Biological: Anti-CEA CAR-T cells; Drug: Capecitabine |
| 3rd Line: NLIR+FU/FA Alone | Active comparator | Patients randomized to the chemotherapy alone treatment arm who developed disease progression during the Bridging Therapy Period while receiving nab paclitaxel plus gemcitabine will be treated with nanoliposomal irinotecan plus fluorouracil/leucovorin during the Treatment Period. Receives: Drug: NLIR+FU/FA |
| 3rd Line: Capecitabine Alone | Active comparator | Patients that developed disease progression during the Bridging Therapy Period while receiving nanoliposomal irinotecan plus 5-FU/leucovorin will be treated with capecitabine during the Treatment Period. Receives: Drug: Capecitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess efficacy by overall survival
As a measure of activity, Overall Survival (OS) will be assessed. The events for the assessment of OS are death events. Time to event endpoints will be estimated using Kaplan-Meier methods. Point estimates and 95% confidence intervals will be provided where applicable.
Measured: 6 - 12 months
Secondary outcomes (14)
Assess safety by monitoring adverse events
As a measure of safety, the types, frequencies, and severities of adverse events and their relationship to study drug will be summarized.
Measured: 6 - 12 months
Assess efficacy by within-liver progression free survival (PFS)
As a measure of activity, within-liver PFS will be assessed. The events for the assessment of within-liver PFS will be measured from the date of randomization to the date of disease progression within the liver or death, whichever comes first. This time to event endpoint will be estimated using Kaplan-Meier methods. Point estimates and 95% confidence intervals will be provided where appropriate.
Measured: 6 - 12 months
Assess efficacy by progression free survival (PFS)
As a measure of activity, PFS will be assessed. The events for the assessment of PFS will be measured from the date of randomization to the date of disease progression or death, whichever comes first. This time to event endpoint will be estimated using Kaplan-Meier methods. Point estimates and 95% confidence intervals will be provided where appropriate.
Measured: 6 - 12 months
Assess efficacy by within-liver time to progression (TTP)
As a measure of activity, within-liver TTP will be assessed. The events for the assessment of within-liver TTP will be measured from the date of randomization to the date of disease progression within the liver. This time to event endpoint will be estimated using Kaplan-Meier methods. Point estimates and 95% confidence intervals will be provided where appropriate.
Measured: 6 - 12 months
Assess efficacy by time to progression (TTP)
As a measure of activity, TTP will be assessed. The events for the assessment of TTP will be measured from the date of randomization to the date of disease progression. This time to event endpoint will be estimated using Kaplan-Meier methods. Point estimates and 95% confidence intervals will be provided where appropriate.
Measured: 6 - 12 months
Assess efficacy by within-liver radiographic response rate using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
As a measure of activity, overall response rate within-liver will be assessed using radiographic scans using RECIST v 1.1 criteria. Response will be assessed for each patient over a 6- to 12-month timeframe during the Treatment and Observation Periods of the protocol.
Measured: 6 - 12 months
Assess efficacy by overall whole-body radiographic response rate using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
As a measure of activity, overall response rate for overall whole-body will be assessed using radiographic scans using RECIST v 1.1 criteria. Response will be assessed for each patient over a 6- to 12-month timeframe during the Treatment and Observation Periods of the protocol.
Measured: 6 - 12 months
Assess efficacy by duration of response within-liver in accordance with RECIST v 1.1 criteria
As a measure of activity, duration of response within-liver will be measured using radiologic scans and assessed according to RECIST v1.1 criteria. This will be assessed for each patient over a 6- to 12-month timeframe during the Treatment and Observation Periods of the protocol.
Measured: 6 - 12 months
Assess efficacy by duration of response of overall whole-body in accordance with RECIST v 1.1 criteria
As a measure of activity, duration of response of overall whole-body will be measured using radiologic scans and assessed according to RECIST v1.1 criteria. This will be assessed for each patient over a 6- to 12-month timeframe during the Treatment and Observation Periods of the protocol.
Measured: 6 - 12 months
Assess efficacy by serologic response rates by CEA levels
As a measure of activity, overall response rate will be assessed by serologic CEA levels. Response rate will be assessed for each patient over a 6- to 12-month timeframe during the Treatment and Observation Periods of the protocol.
Measured: 6 - 12 months
Assess efficacy by serologic response rates by CA 19-9 levels
As a measure of activity, overall response rate will be assessed by serologic CA 19-9 levels. Response rate will be assessed for each patient over a 6- to 12-month timeframe during the Treatment and Observation Periods of the protocol.
Measured: 6 - 12 months
Evaluation of Quality-of-Life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
As a measure of quality-of-life, the EORTC QLQ-C30 instrument will be administered at months 2, 4, 6 of the Treatment Period and at the end of study.
Measured: 6 - 12 months
Evaluation of Quality-of-Life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Pancreatic Cancer Module (EORTC QLQ-PAN26)
As a measure of quality-of-life specific for patients with pancreatic cancer, the EORTC QLQ-PAN26 instrument will be administered at months 2, 4, 6 of the Treatment Period and at the end of study.
Measured: 6 - 12 months
Evaluation of Quality-of-Life using the 5-level EQ-5D version (EQ-5D-5L) questionnaire
As a measure of quality-of-life, the EQ-5D-5L questionnaire will be administered at months 2, 4, 6 of the Treatment Period and at the end of study.
Measured: 6 - 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2019
- Study start1 Nov 2021 (estimated)
- Primary completion1 Jan 2022 (estimated)
- Study completion1 Jan 2022 (estimated)
Why it stopped: Sponsor terminated
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant Tumor of Pancreas Metastatic to LiverStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sorrento Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ying Yan, MD MS, Study director, Sorrento Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04037241
- Sponsor's protocol ID
- STI-CEA-201
- Status last verified
- Mar 2022
- First submitted
- 26 Jul 2019
- Last updated
- 1 Apr 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Open-Label Phase 2b Study of Hepatic Infusions of Anti-CEA CAR-T Cells Alternating With Systemic Chemotherapy Versus Chemotherapy Alone In Patients With Liver Metastases Due To CEA-Expressing Pancreatic Adenocarcinoma
- ClinicalTrials.gov ID
- NCT04037241
- Acronym / sponsor ID
- STI-CEA-201
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Sponsor terminated
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Sorrento Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 1 Nov 2021 (estimated)
- Primary completion
- 1 Jan 2022 (estimated)
- Study completion
- 1 Jan 2022 (estimated)
- First posted
- 30 Jul 2019 (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 is a randomized open-label phase 2b study of the efficacy and safety of regional infusion therapy with Anti-CEA CAR-T cells using the hepatic immunotherapy for metastases (HITM) method and the Trisalus pressure enabling drug delivery (PEDD) device alternating with systemic chemotherapy versus chemotherapy alone in patients with CEA-expressing pancreatic adenocarcinoma with liver metastases.
Detailed description
The study consists of 5 periods: Screening/Leukapheresis Period, Bridging Therapy Period, Randomization Period, Treatment Period, and Observation Period (which will be the long-term follow-up period to monitor for overall survival and long-term safety).
Patients in this trial with CEA-expressing pancreatic adenocarcinoma with liver metastases must have developed disease progression after first-line treatment with FOLFIRINOX (irinotecan, 5-fluorouracil, leucovorin, and oxaliplatin) or gemcitabine-based chemotherapy. Patients will be randomized to either the "anti-CEA CAR-T Cells + systemic chemotherapy treatment arms", or the "chemotherapy alone treatment arms."
If the patients achieve at least stable disease during the Bridging Therapy Period, they will be in the Second-Line Group of Treatment Arms. Patients who develop disease progression during the Bridging Period will be in the Third-Line Group of Treatment Arms.
Patients in the Second-Line or Third-Line treatment arms who are randomized to the treatment arms of "Anti-CEA CAR-T cells plus systemic chemotherapy" will receive hepatic infusions of Anti-CEA CAR-T cells in Cycles 1 and 3 (ie, each 42-day cycle is 3 weekly doses of Anti-CEA CAR-T cells administered as hepatic arterial infusions using a PEDD device with low dose systemic IL-2 support), alternating with the systemic chemotherapy regimen they received during the Bridging Therapy Period in Cycle 2 and Cycles >= 4. Systemic chemotherapy will be administered in 28-day cycles until the development of disease progression.
Patients in the Second-Line or Third-Line treatment arms who are randomized to the treatment arms "chemotherapy alone" arms will continue to receive the same systemic chemotherapy that they received during the Bridging Therapy Period. Systemic chemotherapy will be administered in 28-day or 21-day cycles (depending on the type of systemic chemotherapy regimen the patient will receive) until the development of disease progression.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| 2nd Line: Anti-CEA CAR-T Cells + gemcitabine/nab paclitaxel | Experimental | Biological: Anti-CEA CAR-T cells, Drug: gemcitabine/nab paclitaxelPatients in the "anti-CEA CAR-T Cells plus gemcitabine/nab paclitaxel arm" will have achieved at least stable disease during the Bridging Therapy Period with gemcitabine/nab paclitaxel, and will receive the CAR-T cells in Cycles 1 and 3 and the gemcitabine/nab paclitaxel regimen they received during the Bridging Therapy Period in Cycle 2 and Cycles ≥ 4 of the Treatment Period. Treatment will continue until the development of disease progression. |
| 2nd Line: Anti-CEA CAR-T Cells Plus NLIR+FU/FA | Experimental | Biological: Anti-CEA CAR-T cells, Drug: NLIR+FU/FAPatients in the "anti-CEA CAR-T Cells plus and nanolipsomal irinotecan (NLIR) + Fluorouracil/folinic acid (FU/FA)" will have achieved at least stable disease during the Bridging Therapy Period with NLIR + FU/FA, and will receive the CAR-T cells in Cycles 1 and 3 and the NLIR/FU/FA regimen they received during the Bridging Therapy Period in Cycle 2 and Cycles ≥ 4 of the Treatment Period. Treatment will continue until the development of disease progression. |
| 2nd Line: Gemcitabine /nab paclitaxel Alone | Active comparator | Drug: gemcitabine/nab paclitaxelPatients in the chemotherapy alone treatment arm who achieved at least stable disease during the Bridging Therapy Period while receiving gemcitabine plus nab paclitaxel will continue treatment with the chemotherapy regimen they received during the Treatment Period. This regimen will be administered in 28-day cycles until the development of disease progression. |
| 2nd Line: NLIR + FU/FA Alone | Active comparator | Drug: NLIR+FU/FAPatients in the chemotherapy alone treatment arm who achieved at least stable disease during the Bridging Therapy Period while receiving nanoliposomal irinotecan (NLIR) + Fluorouracil/folinic acid (FU/FA) will continue treatment with the chemotherapy regimen they received during the Treatment Period. This regimen will be administered in 28-day cycles until the development of disease progression. |
| 3rd Line: Anti-CEA CAR-T Cells Plus NLIR+FU/FA | Experimental | Biological: Anti-CEA CAR-T cells, Drug: NLIR+FU/FAPatients randomized to the anti-CEA CAR-T Cells plus chemotherapy treatment arm who developed disease progression during the Bridging Therapy Period will receive the CAR-T cells in Cycles 1 and 3. Nanoliposomal irinotecan plus fluorouracil/leucovorin chemotherapy will be administered in Cycle 2 and Cycles ≥ 4 of the Treatment Period to patients who progressed on nab paclitaxel plus gemcitabine during the Bridging Therapy Period. Treatment will continue until the development of disease progression. |
| 3rd Line: Anti-CEA CAR-T Cells Plus Capecitabine | Experimental | Biological: Anti-CEA CAR-T cells, Drug: CapecitabinePatients randomized to the anti-CEA CAR-T Cells plus chemotherapy treatment arm who developed disease progression during the Bridging Therapy Period will receive the CAR-T cells in Cycles 1 and 3. Capecitabine chemotherapy will be administered in Cycle 2 and Cycles ≥ 4 of the Treatment Period to patients who progressed on nanoliposomal irinotecan fluorouracil/leucovorin during the Bridging Therapy Period. Treatment will continue until the development of disease progression. |
| 3rd Line: NLIR+FU/FA Alone | Active comparator | Drug: NLIR+FU/FAPatients randomized to the chemotherapy alone treatment arm who developed disease progression during the Bridging Therapy Period while receiving nab paclitaxel plus gemcitabine will be treated with nanoliposomal irinotecan plus fluorouracil/leucovorin during the Treatment Period. |
| 3rd Line: Capecitabine Alone | Active comparator | Drug: CapecitabinePatients that developed disease progression during the Bridging Therapy Period while receiving nanoliposomal irinotecan plus 5-FU/leucovorin will be treated with capecitabine during the Treatment Period. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients must have documented CEA-expressing pancreatic adenocarcinoma with unresectable liver metastases. Documentation of CEA-expressing adenocarcinoma may be demonstrated by an elevated serum CEA level (≥ 10 ng/mL) or by the detection of CEA on the cell surface of adenocarcino3.
- Documentation of disease progression of pancreatic adenocarcinoma following the initiation of first-line treatment with FOLFIRINOX or gemcitabine-based therapy.ma cells by immunohistochemistry (IHC).
- The primary pancreatic tumor may be intact and limited lung metastases (≤ 3 lesions, none > 1 cm in longest diameter) and lymphoid metastases (≤ 3 lesions, none > 1 cm in longest diameter) are permitted.
- There must be at least one measurable metastatic liver lesion ( ≥ 10 mm in longest diameter).
- ECOG performance status of 0 or 1.
Key exclusion criteria (19 listed)
- Received anti-cancer chemotherapy or investigational systemic anti-cancer treatments other than first line FOLFIRINOX or gemcitabine-based chemotherapy for advanced pancreatic adenocarcinoma.
- Received FOLFIRINOX or gemcitabine-based therapy within 14 days before receiving the first dose of study treatment.
- Have any unresolved toxicity > Grade 1 from previous anticancer therapy, except for stable chronic toxicities (≤ Grade 2) that are not expected to resolve.
- Have a history of histologically confirmed metastases outside the liver, lungs, or lymph nodes.
- More than 50% replacement of one or both hepatic lobes with tumor.
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 |
|---|---|---|
| Anti-CEA CAR-T cellsAlso: SureFire Precision Infusion System, K171355, TriSalus PEDDDoses will be delivered by hepatic arterial infusions using a pressure enabled drug delivery (PEDD) device | Biological | 2nd Line: Anti-CEA CAR-T Cells + gemcitabine/nab paclitaxel, 2nd Line: Anti-CEA CAR-T Cells Plus NLIR+FU/FA, 3rd Line: Anti-CEA CAR-T Cells Plus Capecitabine, 3rd Line: Anti-CEA CAR-T Cells Plus NLIR+FU/FA |
| gemcitabine/nab paclitaxelAlso: Gemzar, Abraxanesystemic chemotherapy regimen | Drug | 2nd Line: Anti-CEA CAR-T Cells + gemcitabine/nab paclitaxel, 2nd Line: Gemcitabine /nab paclitaxel Alone |
| NLIR+FU/FAAlso: Onivyde, Adrucil, Leucovorinsystemic chemotherapy regimen | Drug | 2nd Line: Anti-CEA CAR-T Cells Plus NLIR+FU/FA, 2nd Line: NLIR + FU/FA Alone, 3rd Line: Anti-CEA CAR-T Cells Plus NLIR+FU/FA, 3rd Line: NLIR+FU/FA Alone |
| CapecitabineAlso: Xelodasystemic chemotherapy regimen | Drug | 3rd Line: Anti-CEA CAR-T Cells Plus Capecitabine, 3rd Line: Capecitabine Alone |
Primary outcome
Assess efficacy by overall survival
Time frame: 6 - 12 months
As a measure of activity, Overall Survival (OS) will be assessed. The events for the assessment of OS are death events. Time to event endpoints will be estimated using Kaplan-Meier methods. Point estimates and 95% confidence intervals will be provided where applicable.
14 secondary outcomes
Assess safety by monitoring adverse events
Time frame: 6 - 12 months
Assess efficacy by within-liver progression free survival (PFS)
Time frame: 6 - 12 months
Assess efficacy by progression free survival (PFS)
Time frame: 6 - 12 months
Assess efficacy by within-liver time to progression (TTP)
Time frame: 6 - 12 months
Assess efficacy by time to progression (TTP)
Time frame: 6 - 12 months
Assess efficacy by within-liver radiographic response rate using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
Time frame: 6 - 12 months
Assess efficacy by overall whole-body radiographic response rate using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
Time frame: 6 - 12 months
Assess efficacy by duration of response within-liver in accordance with RECIST v 1.1 criteria
Time frame: 6 - 12 months
Assess efficacy by duration of response of overall whole-body in accordance with RECIST v 1.1 criteria
Time frame: 6 - 12 months
Assess efficacy by serologic response rates by CEA levels
Time frame: 6 - 12 months
Assess efficacy by serologic response rates by CA 19-9 levels
Time frame: 6 - 12 months
Evaluation of Quality-of-Life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
Time frame: 6 - 12 months
Evaluation of Quality-of-Life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Pancreatic Cancer Module (EORTC QLQ-PAN26)
Time frame: 6 - 12 months
Evaluation of Quality-of-Life using the 5-level EQ-5D version (EQ-5D-5L) questionnaire
Time frame: 6 - 12 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2022.
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Active, not recruiting
Enhanced Outpatient Symptom Management to Reduce Acute Care Visits Due to Chemotherapy-Related Adverse Events
Clinical Stage IV Esophageal Adenocarcinoma AJCC v8, Clinical Stage IV Esophageal Squamous Cell Carcinoma AJCC v8
Recruiting
High Dose-Rate Brachytherapy for the Treatment of Both Primary and Secondary Unresectable Liver Malignancies
Liver Malignant Tumors, Cholangiocarcinoma Metastatic
Recruiting
Virtual Reality for GI Cancer Pain to Improve Patient Reported Outcomes
Cancer Pain, Visceral Pain
RecruitingPhase 2
Testing the Use of Chemotherapy After Surgery for High-Risk Pancreatic Neuroendocrine Tumors
Metastatic Malignant Neoplasm in the Liver, Pancreatic Neuroendocrine Tumor
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.
Ying Yan, MD MS study director
Sorrento Therapeutics
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Anti-CEA CAR-T cells, gemcitabine/nab paclitaxel and NLIR+FU/FA in people with Malignant Tumor of Pancreas Metastatic to Liver, run by Sorrento Therapeutics, Inc..
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 19 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: withdrawn, as of the sponsor's last update on 1 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
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 combined 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.
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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Assess efficacy by overall survival (time frame: 6 - 12 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 1 Apr 2022.