40 Participants Needed

Regorafenib + Durvalumab for Biliary Tract Cancer

Recruiting at 4 trial locations
KN
Overseen ByKUCC Navigation
Age: 18+
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: University of Kansas Medical Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

What is the purpose of this trial?

The purpose of this study is to measure how effective combining Durvalumab and Regorafenib will be for participants with advance stage biliary track carcinoma who have received one line of prior treatment

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot use other investigational agents or certain cancer treatments while participating. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Regorafenib and Durvalumab for treating biliary tract cancer?

Durvalumab, when combined with other drugs like gemcitabine and cisplatin, has shown to improve survival in advanced biliary tract cancer. Regorafenib has also demonstrated clinical activity in advanced biliary tract cancers and may work well with immune therapies like Durvalumab.12345

Is the combination of Regorafenib and Durvalumab safe for humans?

Durvalumab has been studied for safety in various cancers, including biliary tract cancer, and is generally considered safe, though liver injury has been noted as a potential side effect. Regorafenib has shown clinical activity in biliary tract cancers, and while specific safety data for the combination with Durvalumab is not detailed, both drugs have been evaluated for safety in other settings.12367

How is the drug combination of Regorafenib and Durvalumab unique for treating biliary tract cancer?

The combination of Regorafenib and Durvalumab is unique because it combines a drug that modulates the immune system (Regorafenib) with an immune checkpoint inhibitor (Durvalumab), potentially enhancing the body's ability to fight cancer by boosting immune response, which is different from standard chemotherapy treatments.12345

Research Team

Raed Al Rajabi

Raed Al-Rajabi

Principal Investigator

University of Kansas Medical Center

Eligibility Criteria

This trial is for adults with advanced biliary tract cancers that have worsened after one prior treatment. Participants must be able to swallow pills, have a life expectancy of at least 3 months, and an ECOG performance status of 0-1 (fully active or restricted in physically strenuous activity but ambulatory). They should not have had cancer therapy within the last 21 days and must use effective contraception.

Inclusion Criteria

My condition worsened after at least one treatment.
My organ functions are within normal ranges according to recent tests.
Life expectancy of at least 3 months
See 10 more

Exclusion Criteria

I haven't had any major abdominal issues like a fistula or obstruction in the last 8 weeks.
I do not have any serious ongoing illnesses like heart failure or lung disease.
I have been treated with immune checkpoint inhibitors before.
See 30 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Finding

3 + 3 design with two dose levels of 80 mg and 120 mg to discover the Maximum Tolerated Dose (MTD) for regorafenib

4 weeks
1 visit per week (in-person)

Treatment

Participants receive Regorafenib and Durvalumab; each cycle is 28 days

Up to 2 years
1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • Durvalumab
  • Regorafenib
Trial OverviewThe study tests the combination of Durvalumab and Regorafenib on patients with advanced stage biliary tract carcinoma who've already tried one treatment without success. The goal is to see if this drug duo can safely improve their condition.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Dose Finding RegorafenibExperimental Treatment2 Interventions
We will use a 3 + 3 design with two dose levels of 80 mg and 120 mg to discover the Maximum Tolerated Dose (MTD) for regorafenib

Durvalumab is already approved in European Union, United States, Japan for the following indications:

🇪🇺
Approved in European Union as Imfinzi for:
  • Locally advanced, unresectable non-small cell lung cancer (NSCLC)
🇺🇸
Approved in United States as Imfinzi for:
  • Extensive-stage small cell lung cancer (ES-SCLC)
  • Limited-stage small cell lung cancer (LS-SCLC)
  • Locally advanced or metastatic urothelial carcinoma
🇯🇵
Approved in Japan as Imfinzi for:
  • Not specified in provided sources

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Kansas Medical Center

Lead Sponsor

Trials
527
Recruited
181,000+

Findings from Research

In a real-world study of 145 patients with advanced biliary tract cancer, the combination of durvalumab with gemcitabine and cisplatin achieved a median progression-free survival (PFS) of 8.9 months and a median overall survival (OS) of 12.9 months, confirming the efficacy seen in the TOPAZ-1 trial.
The treatment was associated with a high rate of adverse events (94.5%), with 35.2% experiencing severe (grades 3-4) adverse events, but only 2.1% had severe immune-mediated adverse events, indicating a manageable safety profile.
Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer: An early exploratory analysis of real-world data.Rimini, M., Fornaro, L., Lonardi, S., et al.[2023]
In a phase II trial involving 34 patients with advanced biliary tract cancers, the combination of regorafenib and avelumab showed antitumor activity, with a partial response in 13.8% of patients and stable disease in 37.9%.
The treatment was associated with manageable safety concerns, primarily hypertension and fatigue, and the presence of certain biomarkers like high levels of programmed cell death ligand 1 was linked to better outcomes, suggesting potential for personalized treatment approaches.
Regorafenib-avelumab combination in patients with biliary tract cancer (REGOMUNE): a single-arm, open-label, phase II trial.Cousin, S., Cantarel, C., Guegan, JP., et al.[2022]
In the safety run-in of the IMMUNOBIL PRODIGE 57 trial involving 20 patients, the combination of durvalumab and tremelimumab with paclitaxel resulted in a high rate of dose-limiting toxicities (50%), including serious anaphylactic reactions and other severe adverse events.
Due to the safety concerns raised by the combination therapy, the trial will proceed with only the durvalumab and tremelimumab combination, indicating that the addition of paclitaxel may not be safe for patients with advanced biliary tract carcinoma.
Triplet combination of durvalumab, tremelimumab, and paclitaxel in biliary tract carcinomas: Safety run-in results of the randomized IMMUNOBIL PRODIGE 57 phase II trial.Boilève, A., Hilmi, M., Gougis, P., et al.[2021]

References

Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer: An early exploratory analysis of real-world data. [2023]
Regorafenib-avelumab combination in patients with biliary tract cancer (REGOMUNE): a single-arm, open-label, phase II trial. [2022]
Triplet combination of durvalumab, tremelimumab, and paclitaxel in biliary tract carcinomas: Safety run-in results of the randomized IMMUNOBIL PRODIGE 57 phase II trial. [2021]
Durvalumab: A Review in Advanced Biliary Tract Cancer. [2023]
Regorafenib after failure of gemcitabine and platinum-based chemotherapy for locally advanced/metastatic biliary tumors: REACHIN, a randomized, double-blind, phase II trial. [2022]
Liver injury during durvalumab-based immunotherapy is associated with poorer patient survival: A retrospective analysis. [2023]
Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]