Regorafenib + Durvalumab for Biliary Tract Cancer

Recruiting in Palo Alto (17 mi)

+4 other locations

Overseen by Raed Al-Rajabi

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: University of Kansas Medical Center

Must not be taking: Herbal remedies

Disqualifiers: Pregnancy, Autoimmune disease, HIV, others

No Placebo Group

Breakthrough Therapy

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.

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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.

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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.

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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

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.

Trial 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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Kansas Cancer Center - North Kansas City, MO

University of Kansas Cancer Center - Lee's Summit Lee's Summit, MO

The University of Kansas Medical Center North Kansas City, MO

University of Kansas Cancer Center - Overland Park Overland Park, KS

More Trial Locations

Who Is Running the Clinical Trial?

University of Kansas Medical Center Lead Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer: An early exploratory analysis of real-world data. [2023] The TOPAZ-1 phase III trial reported a survival benefit with the anti-programmed death cell ligand 1 (anti-PD-L1) durvalumab in combination with gemcitabine and cisplatin in patients with advanced biliary tract cancer. The present study investigated the efficacy and safety of this new standard treatment in a real-world setting.

2. England pubmed.ncbi.nlm.nih.gov

Regorafenib-avelumab combination in patients with biliary tract cancer (REGOMUNE): a single-arm, open-label, phase II trial. [2022] Regorafenib has shown substantial clinical activity in patients with advanced biliary tract cancers (BTCs). Preclinical data suggested that this drug modulates antitumour immunity and is synergistic with immune checkpoint inhibition.

3. England 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. [2021] The IMMUNOBIL PRODIGE 57 trial is a non-comparative randomized phase II study assessing the efficacy and safety of the durvalumab (an anti-PD-L1) and tremelimumab (an anti-CTLA4) combination with or without weekly paclitaxel in patients with advanced biliary tract carcinoma (BTC) after failure of platinum-based chemotherapy. Taxanes have already been safely combined with immune checkpoint inhibitors in other tumors. We report results of the 20-patient safety run-in.

4. France pubmed.ncbi.nlm.nih.gov

Durvalumab: A Review in Advanced Biliary Tract Cancer. [2023] Durvalumab (Imfinzi®), a therapeutic human monoclonal antibody which binds to and blocks the activity of the immunosuppressive programmed death-ligand 1 (PD-L1) protein, is approved in the USA, EU, Japan and other countries in combination with gemcitabine and cisplatin for adults with advanced biliary tract cancer. In the pivotal phase 3 TOPAZ-1 trial, durvalumab plus gemcitabine and cisplatin significantly prolonged overall survival and progression-free survival compared with placebo plus gemcitabine and cisplatin in adults with advanced biliary tract cancer. Benefit from durvalumab was seen irrespective of primary tumour location, disease status at diagnosis (unresectable or recurrent), or initial levels of PD-L1 expression. The tolerability of durvalumab plus gemcitabine and cisplatin was manageable. Overall, the addition of durvalumab to gemcitabine and cisplatin is a valuable new treatment option for adults with advanced biliary tract cancer.

5. England 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. [2022] There is a high unmet clinical need for treatments of advanced/metastatic biliary tract cancers after progression on first-line chemotherapy. Regorafenib has demonstrated efficacy in some gastrointestinal tumors that progress on standard therapies.

6. Switzerland pubmed.ncbi.nlm.nih.gov

Liver injury during durvalumab-based immunotherapy is associated with poorer patient survival: A retrospective analysis. [2023] Durvalumab is approved for the treatment of lung cancer, advanced biliary tract cancers, and is also being evaluated in many other solid organ tumors. The aim of our study is to define the incidence, etiology, and outcomes of liver injury in consecutive patients receiving durvalumab-based immunotherapy.

7. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022] The prominent immune checkpoint molecule, programmed cell death ligand-1 (PD-L1), is the object of increasing attention. Here, we report a meta-analysis investigating the safety and efficacy of durvalumab (MEDI4736), an inhibitor of PD-L1, in various solid tumors.