Regorafenib + Durvalumab for Biliary Tract Cancer

Recruiting at 4 trial locations

Overseen By KUCC Navigation

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Kansas Medical Center

Must not be taking: Herbal remedies

Disqualifiers: Pregnancy, Autoimmune disease, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 2

Duration: Up to 2 years

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of combining two treatments, Durvalumab (an immunotherapy drug) and Regorafenib (a targeted therapy drug), for individuals with advanced biliary tract cancer. Researchers aim to determine how well these medications work together in patients who have tried at least one previous treatment but still experience cancer progression. Participants should have biliary tract cancer that cannot be surgically removed or has spread, and must have already undergone one line of therapy without success. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that regorafenib has been tested for safety in treating biliary tract cancer. One study tested regorafenib alone in patients with advanced biliary tract cancer, and the results indicated that the treatment was generally well-tolerated. However, some patients experienced side effects, such as tiredness, high blood pressure, and hand-foot skin reactions.

Durvalumab, the other treatment in this trial, has FDA approval for other types of cancer, indicating a well-known safety record. Previous studies have reported common side effects of durvalumab, including tiredness, muscle pain, and nausea.

Overall, both treatments have undergone safety studies, and while side effects can occur, they are usually manageable. Clinical trial participants are closely monitored to address any issues quickly. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for biliary tract cancer involve chemotherapy, which attacks rapidly dividing cells, but can also harm healthy cells. However, regorafenib and durvalumab offer a unique approach. Regorafenib works by inhibiting specific proteins that promote tumor growth, potentially slowing or stopping the cancer. Durvalumab, an immunotherapy, boosts the body's immune system to better recognize and fight cancer cells. Researchers are excited about combining these treatments because they target the cancer in two different ways, offering hope for more effective and personalized treatment options.

What evidence suggests that combining Durvalumab and Regorafenib might be an effective treatment for biliary tract cancer?

Research has shown that regorafenib holds promise for treating advanced biliary tract cancer. Studies have found that patients who received previous treatments lived longer without their cancer worsening and experienced better tumor control with regorafenib. In one study, 62.1% of patients experienced tumor shrinkage, known as a partial response. In this trial, participants will receive regorafenib, with the dose determined through a dose-finding process. Durvalumab, another treatment option, helps the immune system attack cancer cells more effectively. Combining durvalumab with regorafenib might enhance the overall response, as they work in different ways to combat cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Raed Al-Rajabi

Principal Investigator

University of Kansas Medical Center

Are You a Good Fit for This Trial?

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

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Regorafenib

Trial Overview The 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.

How Is the Trial Designed?

Group I: Dose Finding Regorafenib Experimental Treatment 2 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

Who Is Running the Clinical Trial?

University of Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

Published Research Related to This Trial

In a study of 112 patients receiving durvalumab for cancer treatment, 19% experienced liver injury, which was linked to higher rates of tumor progression and mortality, indicating that liver injury may be a significant concern in this patient population.

Among the liver injury cases, 29% were classified as probable drug-induced liver injury (DILI) related to durvalumab, but these cases were generally mild and self-limited, suggesting that while monitoring for liver injury is important, severe complications are rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver injury during durvalumab-based immunotherapy is associated with poorer patient survival: A retrospective analysis. Swanson, LA., Kassab, I., Tsung, I., et al.[2023]

In the phase 3 TOPAZ-1 trial, the combination of durvalumab with gemcitabine and cisplatin significantly improved overall survival and progression-free survival in adults with advanced biliary tract cancer, compared to the placebo group.

Durvalumab's benefits were consistent across various patient factors, including tumor location and PD-L1 expression levels, and the treatment was found to be manageable in terms of tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: A Review in Advanced Biliary Tract Cancer. Fung, S., Syed, YY.[2023]

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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 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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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 study involving 66 patients with advanced biliary tract cancers, regorafenib significantly improved progression-free survival (PFS) to a median of 3.0 months compared to 1.5 months for placebo, indicating its efficacy as a second-line treatment.

Regorafenib also demonstrated a higher rate of stable disease (74% vs. 34% with placebo), suggesting better tumor control, while safety profiles showed no unexpected adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regorafenib after failure of gemcitabine and platinum-based chemotherapy for locally advanced/metastatic biliary tumors: REACHIN, a randomized, double-blind, phase II trial. Demols, A., Borbath, I., Van den Eynde, M., 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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7787270/

A Multi-Institutional Phase 2 Trial of Regorafenib in ... Regorafenib demonstrated modest clinical efficacy in heavily pretreated patients with BTC. Further exploration of biomarkers is warranted to ...

2. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.31872

A phase 2 trial of regorafenib as a single agent in patients with ... The current results suggest promising efficacy of regorafenib in patients with chemotherapy-refractory, advanced/metastatic biliary tract cancer ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30561756/

A phase 2 trial of regorafenib as a single agent in patients with ... Conclusions: The current results suggest promising efficacy of regorafenib in patients with chemotherapy-refractory, advanced/metastatic biliary ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(20)39839-2/fulltext

REACHIN, a randomized, double-blind, phase II trial Regorafenib significantly improved PFS and tumor control in patients with previously treated metastatic/unresectable biliary tract cancer in the ...

5. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1449211/full

Chemotherapy combined with regorafenib and immune ... Results: Among the patients, 0 patient achieved complete response, 18 patients (62.1%) achieved partial response, 8 patients (27.6%) had stable ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02115542

Single Agent Regorafenib in Refractory Advanced Biliary ... The main purpose of this study is to see if regorafenib can help control or decrease cancer size in patients with cancer of the bile duct.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01853046?term=AREA%5BNCTIdSearch%5D(NCT00960258%20OR%20NCT01096030%20OR%20NCT01117623%20OR%20NCT01287598%20OR%20NCT01322438%20OR%20NCT01339104%20OR%20NCT01853046%20OR%20NCT01973868%20OR%20NCT02001909%20OR%20NCT02106845%20OR%20NCT02168777%20OR%20NCT02466802%20OR%20NCT03406871%20OR%20NCT04116541%20OR%20NCT04200404%20OR%20NCT04704154)&rank=10&tab=results

Pharmacokinetics and Safety of Regorafenib (BAY73-4506 ... A phase of research to describe clinical trials that gather more information about a drug's safety and effectiveness by studying different populations and ...

8. academic.oup.com academic.oup.com/oncolo/article/30/6/oyaf080/8170137

Regorafenib + Gemcitabine-Oxaliplatin in Biliary Tract Cancer Regorafenib, a multikinase inhibitor, shows promise in refractory digestive cancers and may be beneficial with conventional chemotherapy for BTC.