Search Results for 'Durvalumab'
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Search Results
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Durvalumab: an investigational anti-PD-L1 antibody for the treatment of biliary tract cancer
Phase II basket trial of olaparib and durvalumab in patients (pts) with isocitrate dehydrogenase (IDH) mutated solid tumors.
Durvalumab or Placebo in Combination With Gemcitabine/Cisplatin in Patients With 1st Line Advanced Biliary Tract Cancer (TOPAZ-1) (TOPAZ-1)
https://clinicaltrials.gov/ct2/show/NCT03875235
Gavin
A Phase II Trial of Durvalumab (MEDI4736) and Tremelimumab and Radiation Therapy in Hepatocellular Carcinoma and Biliary Tract Cancer
https://clinicaltrials.gov/ct2/show/NCT03482102
Gavin
Durvalumab in Combination With Chemotherapy in Treating Patients With Advanced Solid Tumors, (DURVA+ Study)
https://clinicaltrials.gov/ct2/show/NCT03907475?term=NCT03907475&draw=2&rank=1
Evaluation of T-cell activation in refractory biliary cancers treated with
gemcitabine and checkpoint inhibition
Significance and Background:
The objective of the proposed study is to examine the effects of gemcitabine on immune activation and tumor antigenicity in refractory biliary cancers when used in combination with the PDL-1 inhibitor durvalumab. We propose that gemcitabine will elicit increased tumor antigenicity (i.e., TMB and/or MSI) and will trigger a greater activation of T-cells when combined with durvalumab in comparison with durvalumab alone.
Our detailed investigative approach will identify mechanisms to increase treatment response to ICIs when used in combination with gemcitabine in refractory biliary cancers. We expect that chemotherapy will increase tumor antigenicity (i.e., TMB and MSI) and potentially trigger response to ICI therapy. [1, 2] We will be studying the degree of T-cell activation in response to gemcitabine, which would serve as a marker for immune activation and as a marker for the efficacy of ICI therapy. We will be assessing T-cell activation, TMB and MSI using assays that were developed by our collaborators at the Frederick National Laboratory for Cancer Research. The results from this study would provide preliminary clinical data and proof of concept of increased immune activation, which could potentially result in increased clinical response. With these preliminary data, we anticipate opening an expansion cohort of the gemcitabine and durvalumab combination arm in refractory biliary tumors to confirm these findings and assess response. Thus, the results of this study will have broad and immediate clinical relevance to the treatment of refractory biliary cancers.
Approach:
The proposed study will be performed using biopsy samples from patients with refractory biliary cancers on the “DURVA+: Evaluation of the Safety and Pharmacodynamics of Anti-PD-L1 Antibody MEDI4736 (durvalumab) in Combination with Chemotherapy in Patients with Advanced Solid Tumors” clinical trial (NCT03907475) This large clinical trial evaluates durvalumab, either alone or in combination with 6 different chemotherapeutic agents. The trial enrolls adult patients with advanced solid tumors who have progressed on at least one line of standard therapy (or have tumors for which no standard treatment exists). Patients will be placed onto one of 7 treatment arms (Figure 1) in an unblinded fashion and assignment will determined by the PI or study chair based on histology and prior systemic therapy.
Patients having received prior anti-PD1/PDL-1 will be eligible for arms 2-7. Patients who have not received prior anti- PD1/PDL-1, will be assigned to arm 1 (durvalumab alone); at disease progression, they will be eligible to cross over to one of the chemotherapy arms (arm 2-7), provided they meet all the eligibility criteria, including adequate washout.
Patients with biliary cancers who have not received prior anti-PD1/PDL-1 will be enrolled on arm 1. Those having received prior anti-PD1/PDL-1 agents will preferentially be enrolled on arm 2, due to the potential benefit to gemcitabine in this histology. Prior treatment with gemcitabine will be allowed, and it is expected that the majority of patients with biliary cancer will have received prior gemcitabine-based therapy as part of standard of care.
For the proposed study, we will analyze biopsy samples from a total of 10 patients with refractory biliary cancers who have adequate biopsy samples at multiple timepoints. This will include 5 patients who receive durvalumab alone and 5 who receive durvalumab +gemcitabine.
References
1. Bezu, L., et al., Combinatorial strategies for the induction of immunogenic cell death. Front Immunol, 2015. 6: p. 187.
2. Rizvi, N.A., et al., Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science, 2015. 348(6230): p. 124-8.
Hello everyone,
I would like to introduce myself. My name is KC. My mother was diagnosed with Extrahepatic CC, Stage III. When this happened, I buried myself in medical journals / treatments and burned myself out doing research. I have been visiting here on and off for a while now. I just recently decided to become part of your wonderful community after a very difficult decision I made recently. Of course, all decisions are made by the patient. But as a caregiver, your opinions carry so much weight that the decision is indirectly yours. I’m grateful for finding this site and the wealth of information here is priceless. So much easier to read over doctor jargon.
I tried to get my mother in the TOPAZ-1 clinical trial. However, after 2 attempts, the doctor was not able to collect a biopsy sample via FNA (Fine Needle Aspiration). The option the doctor gave us was that if the surgeon was going to attempt another biopsy, he might have to punch a hole through the bile duct in order to get to the mass. If we were to take that option, treatment would be delayed again for at least another 3 weeks, there may be a complication with the damage to the duct, and ultimately might not even succeed. Since it has already been 12 weeks since Kaiser discovered her cancer, I did not want to delay any treatment any longer and give the tumor the time to grow and metastasize. The second opinion I got from the City of Hope doctor supported Kaiser standard treatment of Gem/Cis ASAP. He also mentioned that just because the FNA failed, doesn’t mean that she cannot attempt another biopsy later on. But without a biopsy to determine is MSI is present, there is no way to for her to be prescribed Pembrolizumab (Keytruda). Participation in the clinical trial would also not allow my mom to receive radiation therapy on the side. So, in front of the doc, I gave my mom all the facts, and recommended she just start Gem/Cis that day. Tomorrow will be her 2nd treatment, 1st cycle. But, weighing the decision of attempting a 3rd biopsy vs. starting Gem/Cis now, still feels heavy on my mind. I’m not sure if I made the right recommendation.
I looked up a full body 3D anatomy model and 3D pancreatic model so I understand how difficult it is to get to the tumor location. Has anyone else experienced difficulty with attaining a biopsy? Is a biopsy taken after chemo treatments still viable for molecular testing? Living in the US, can we seek surgical treatment in Toronto, Canada? Since Kaiser would not cover Proton Therapy, we’ll pay out of pocket for Proton Therapy since California Protons offer a reduction in pricing for people who are denied by their insurance company. These are the questions I’m currently looking into.
I think sharing is therapy for the caregiver. I feel better after writing this. Much love everyone.
Durvalumab or Placebo in Combination With Gemcitabine/Cisplatin in Patients With 1st Line Advanced Biliary Tract Cancer (TOPAZ-1) (TOPAZ-1)
https://clinicaltrials.gov/ct2/show/NCT03875235
Gavin
A Phase II Trial of Durvalumab (MEDI4736) and Tremelimumab and Radiation Therapy in Hepatocellular Carcinoma and Biliary Tract Cancer
https://clinicaltrials.gov/ct2/show/NCT03482102
Gavin
A Phase II Trial of Durvalumab (MEDI4736) and Tremelimumab and Radiation Therapy in Hepatocellular Carcinoma and Biliary Tract Cancer
https://clinicaltrials.gov/ct2/show/NCT03482102
Gavin
Durvalumab or Placebo in Combination With Gemcitabine/Cisplatin in Patients With 1st Line Advanced Biliary Tract Cancer (TOPAZ-1) (TOPAZ-1)
https://clinicaltrials.gov/ct2/show/NCT03875235
Gavin
Durvalumab or Placebo in Combination With Gemcitabine/Cisplatin in Patients With 1st Line Advanced Biliary Tract Cancer (TOPAZ-1) (TOPAZ-1)
https://clinicaltrials.gov/ct2/show/NCT03875235
Gavin
Durvalumab or Placebo in Combination With Gemcitabine/Cisplatin in Patients With 1st Line Advanced Biliary Tract Cancer (TOPAZ-1) (TOPAZ-1)
https://clinicaltrials.gov/ct2/show/NCT03875235
Gavin
A Phase II Trial of Durvalumab (MEDI4736) and Tremelimumab and Radiation Therapy in Hepatocellular Carcinoma and Biliary Tract Cancer
https://clinicaltrials.gov/ct2/show/NCT03482102
Gavin
Durvalumab or Placebo in Combination With Gemcitabine/Cisplatin in Patients With 1st Line Advanced Biliary Tract Cancer (TOPAZ-1) (TOPAZ-1)
https://clinicaltrials.gov/ct2/show/NCT03875235
Gavin
A Phase II Trial of Durvalumab (MEDI4736) and Tremelimumab and Radiation Therapy in Hepatocellular Carcinoma and Biliary Tract Cancer
https://clinicaltrials.gov/ct2/show/NCT03482102
Gavin