TIL Therapy for Biliary Tract Cancer
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Udai Kammula
Must not be taking: Steroids, Anti-infectives
Disqualifiers: Pregnancy, Immunodeficiency, Infections, others
No Placebo Group
Prior Safety Data
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?
This trial uses a special chemotherapy followed by the patient's own lab-grown immune cells and a drug to boost the immune system. It targets patients with advanced biliary tract cancers, which are difficult to treat. The process involves removing tumor cells, growing immune cells in a lab, reducing the patient's existing immune cells, and then infusing the lab-grown cells back into the patient.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications, but it does mention that more than four weeks must have passed since any prior systemic therapy before starting the preparative regimen. This suggests a possible need to pause certain treatments.
What data supports the effectiveness of the treatment Tumor Infiltrating Lymphocytes (TIL), Lifileucel, Amtagvi for biliary tract cancer?
Research on immune checkpoint inhibitors, which are a type of immunotherapy like TIL therapy, shows promising results for advanced biliary tract cancers, with significantly longer survival times compared to traditional chemotherapy. This suggests that treatments harnessing the immune system, such as TIL therapy, may offer hope for improving outcomes in biliary tract cancer.12345
Is TIL therapy safe for humans?
How is TIL therapy different from other treatments for biliary tract cancer?
Research Team
US
Udai S Kammula, MD
Principal Investigator
UPMC Hillman Cancer Center
Eligibility Criteria
This trial is for adults aged 18-75 with advanced, recurrent, or metastatic biliary tract cancers who have not responded to standard treatments. They must be able to handle specific chemotherapy and high-dose aldesleukin, sign informed consent, have an ECOG performance status of 0 or 1 (fully active or restricted in physically strenuous activity but ambulatory), and agree to birth control measures. Those with small, stable brain metastases may qualify.Inclusion Criteria
Able to understand and sign the Informed Consent Document
I agree to use birth control during and up to four months after the study.
I am enrolled in HCC 17-220 and have TIL cultures ready for therapy.
See 11 more
Exclusion Criteria
You have had a serious allergic reaction to any of the medications used in this study in the past.
You are not currently taking any other experimental drugs or treatments.
I do not have any active infections, bleeding disorders, or major illnesses.
See 8 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Cell Preparation
Patients undergo resection or biopsy of tumor to obtain Tumor Infiltrating Lymphocytes (TIL) for growth and expansion.
Variable
Treatment
Participants receive a lymphocyte depleting preparative regimen followed by infusion of TIL and high-dose aldesleukin.
6 weeks (+/- 2 weeks)
Multiple visits for chemotherapy and TIL infusion
Follow-up
Participants are monitored for safety, tumor response, and immunologic parameters after treatment.
Up to 24 months
Treatment Details
Interventions
- Tumor Infiltrating Lymphocytes (TIL) (CAR T-cell Therapy)
Trial OverviewThe study tests the effectiveness of Tumor Infiltrating Lymphocytes (TIL) therapy combined with a non-myeloablative lymphodepleting regimen followed by high-dose aldesleukin in patients with biliary tract cancer. It's a Phase 2 trial aiming to see if this approach can shrink tumors in those who haven't had success with other treatments.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Tumor Infiltrating Lymphocytes (TIL)Experimental Treatment1 Intervention
Patients with locally advanced, recurrent, or metastatic biliary tract cancers will receive the lymphocyte depleting preparative regimen consisting of fludarabine and cyclophosphamide, followed by infusion of up to 2x10\^11 lymphocytes infused intravenously through a central vein catheter and Aldesleukin, administered at a dose of 600,000 IU/kg (based on total body weight) as an intravenous bolus over a 15-minute period approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to a maximum of 6 doses.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Allyson WelschPittsburgh, PA
UPMC Hillman Cancer CenterPittsburgh, PA
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Who Is Running the Clinical Trial?
Udai Kammula
Lead Sponsor
Trials
3
Patients Recruited
350+
Findings from Research
In a study of 30 patients with previously treated HER2-positive metastatic biliary tract cancer, the combination of tucatinib and trastuzumab showed a confirmed objective response rate of 46.7%, indicating significant antitumor activity.
The treatment was generally well tolerated, with common side effects including fever and diarrhea, but no deaths were attributed to treatment-related adverse events, suggesting a favorable safety profile.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Tucatinib and Trastuzumab for Previously Treated Human Epidermal Growth Factor Receptor 2-Positive Metastatic Biliary Tract Cancer (SGNTUC-019): A Phase II Basket Study.Nakamura, Y., Mizuno, N., Sunakawa, Y., et al.[2023]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
The efficiency and safety of immune checkpoint inhibitors for advanced biliary tract cancers based on gene profiles: A retrospectively controlled study.Yao, GL., Fan, YG.[2022]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Immunotherapy as a treatment for biliary tract cancers: A review of approaches with an eye to the future.Blair, AB., Murphy, A.[2019]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): a multicentre, open-label, phase 2a, multiple basket study.Javle, M., Borad, MJ., Azad, NS., et al.[2021]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Reduction of immunosuppressive tumor microenvironment in cholangiocarcinoma by ex vivo targeting immune checkpoint molecules.Zhou, G., Sprengers, D., Mancham, S., et al.[2020]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Safety and Efficacy of Allogeneic Natural Killer Cells in Combination with Pembrolizumab in Patients with Chemotherapy-Refractory Biliary Tract Cancer: A Multicenter Open-Label Phase 1/2a Trial.Leem, G., Jang, SI., Cho, JH., et al.[2022]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Local-regional therapy combined with toripalimab and lenvatinib in patients with advanced biliary tract cancer.Wang, Y., Xun, Z., Yang, X., et al.[2023]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Efficacy and biomarker analysis of nivolumab plus gemcitabine and cisplatin in patients with unresectable or metastatic biliary tract cancers: results from a phase II study.Feng, K., Liu, Y., Zhao, Y., et al.[2022]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Current Progress in Immunotherapy for the Treatment of Biliary Cancers.Pauff, JM., Goff, LW.[2018]
In a study of 130 patients with biliary tract cancer, a high Immunoscore, based on the presence of specific immune cells, was associated with significantly better overall survival (60.8 months vs. 26.4 months) and recurrence-free survival compared to a low Immunoscore.
The high Immunoscore was identified as an independent prognostic factor for both overall survival and recurrence-free survival, indicating its potential as a valuable marker in assessing patient outcomes.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Tumor-infiltrating lymphocytes and macrophages as a significant prognostic factor in biliary tract cancer.Tanaka, R., Eguchi, S., Kimura, K., et al.[2023]
In a study of 35 liver cancer specimens, both hepatocellular and cholangiolar carcinomas showed significant infiltration of tumor-infiltrating lymphocytes (TIL), particularly CD4+ T cells at the tumor/liver interface and CD8+ T cells within the tumor itself.
The presence of these lymphocytes suggests they may play distinct roles in the immune response against liver tumors, although their distribution and quantity did not differ significantly between the two types of cancer.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Liver tumor infiltrating lymphocytes: comparison of hepatocellular and cholangiolar carcinoma.Kasper, HU., Drebber, U., Stippel, DL., et al.[2021]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
High ratio of programmed cell death protein 1 (PD-1)(+)/CD8(+) tumor-infiltrating lymphocytes identifies a poor prognostic subset of extrahepatic bile duct cancer undergoing surgery plus adjuvant chemoradiotherapy.Lim, YJ., Koh, J., Kim, K., et al.[2018]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Preoperative Neutrophil-to-lymphocyte Ratio Predicts Tumor-infiltrating CD8+ T Cells in Biliary Tract Cancer.Tanaka, R., Kimura, K., Eguchi, S., et al.[2020]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
A phase II trial of gemcitabine, irinotecan and panitumumab in advanced cholangiocarcinoma.Sohal, DP., Mykulowycz, K., Uehara, T., et al.[2022]
References
Tucatinib and Trastuzumab for Previously Treated Human Epidermal Growth Factor Receptor 2-Positive Metastatic Biliary Tract Cancer (SGNTUC-019): A Phase II Basket Study. [2023]
The efficiency and safety of immune checkpoint inhibitors for advanced biliary tract cancers based on gene profiles: A retrospectively controlled study. [2022]
Immunotherapy as a treatment for biliary tract cancers: A review of approaches with an eye to the future. [2019]
Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): a multicentre, open-label, phase 2a, multiple basket study. [2021]
Reduction of immunosuppressive tumor microenvironment in cholangiocarcinoma by ex vivo targeting immune checkpoint molecules. [2020]
Safety and Efficacy of Allogeneic Natural Killer Cells in Combination with Pembrolizumab in Patients with Chemotherapy-Refractory Biliary Tract Cancer: A Multicenter Open-Label Phase 1/2a Trial. [2022]
Local-regional therapy combined with toripalimab and lenvatinib in patients with advanced biliary tract cancer. [2023]
Efficacy and biomarker analysis of nivolumab plus gemcitabine and cisplatin in patients with unresectable or metastatic biliary tract cancers: results from a phase II study. [2022]
Current Progress in Immunotherapy for the Treatment of Biliary Cancers. [2018]
Tumor-infiltrating lymphocytes and macrophages as a significant prognostic factor in biliary tract cancer. [2023]
Liver tumor infiltrating lymphocytes: comparison of hepatocellular and cholangiolar carcinoma. [2021]
High ratio of programmed cell death protein 1 (PD-1)(+)/CD8(+) tumor-infiltrating lymphocytes identifies a poor prognostic subset of extrahepatic bile duct cancer undergoing surgery plus adjuvant chemoradiotherapy. [2018]
Preoperative Neutrophil-to-lymphocyte Ratio Predicts Tumor-infiltrating CD8+ T Cells in Biliary Tract Cancer. [2020]
A phase II trial of gemcitabine, irinotecan and panitumumab in advanced cholangiocarcinoma. [2022]