Radiation + Immunotherapy for Bile Duct Cancer

Overseen By Eugene J. Koay

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immune checkpoint inhibitors, Systemic steroids

Disqualifiers: Pregnancy, Uncontrolled illness, Recent surgery, others

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

Compensation: Varies

Number of Visits: 27

2 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial is to find out the best dose, possible benefits, and/or side effects of hypofractionated radiation therapy and bintrafusp alfa in treating patients with bile duct cancer that has spread to other places in the body (advanced intrahepatic cholangiocarcinoma). Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Immunotherapy with bintrafusp alfa, a bifunctional fusion protein composed of the monoclonal antibody avelumab and TGF-beta, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The combination of hypofractionated radiation therapy and bintrafusp alfa may help to control intrahepatic cholangiocarcinoma.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on certain immune-based treatments or high doses of steroids. If you have taken any anticancer medication recently, you may need to wait before starting the trial.

What data supports the effectiveness of the treatment for bile duct cancer?

Research shows that bintrafusp alfa, a drug targeting specific proteins involved in cancer growth, has shown effectiveness in treating various solid tumors, including biliary tract cancers. Additionally, hypofractionated radiation therapy, a type of radiation treatment given in larger doses over fewer sessions, has been effective and well-tolerated in patients with unresectable biliary tract cancer, improving survival rates. ^{1 2 3 4 5}

Is the combination of radiation and immunotherapy safe for treating bile duct cancer?

The combination of bintrafusp alfa (an immunotherapy) and hypofractionated radiation therapy (a type of radiation treatment) has been studied for safety in various cancers. Bintrafusp alfa has shown clinical efficacy in multiple solid tumors, and hypofractionated radiation therapy has been well tolerated in studies, with no patients developing severe toxicities in a study on biliary tract cancer. ^{2 3 4 6 7}

How is the treatment of Radiation + Immunotherapy for Bile Duct Cancer unique?

This treatment is unique because it combines bintrafusp alfa, a novel drug that targets both TGF-β and PD-L1 to enhance the immune response, with hypofractionated radiation therapy, which delivers higher doses of radiation in fewer sessions, potentially improving outcomes for patients with limited treatment options. ^{1 3 4 5 8}

Research Team

Eugene J. Koay

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with advanced bile duct cancer who have tried at least one chemotherapy or refused it. They must have two measurable tumors, be in good physical condition, and agree to use birth control. People can't join if they have autoimmune diseases, recent infections requiring antibiotics, major surgery within 4 weeks, received certain treatments recently, untreated brain metastases, are pregnant or breastfeeding.

Inclusion Criteria

Total bilirubin < 1.5 x institutional upper limit of normal (IULN)

I am fully active or have minor restrictions in physical activity.

I have undergone or refused initial chemotherapy.

Exclusion Criteria

Patients who are pregnant or lactating

I have not had major bleeding in the last 4 weeks.

I haven't taken cancer drugs in the last 21 days and don't have major side effects from past treatments.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Therapy

Patients undergo hypofractionated radiation therapy once daily on weekdays for 15 fractions

3 weeks

15 visits (in-person)

Treatment with Bintrafusp Alfa

Patients receive bintrafusp alfa intravenously over 1 hour on day 1, with cycles repeating every 14 days for up to 2 years

Up to 2 years

Bi-weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Every 12 weeks (in-person)

Treatment Details

Interventions

• Bintrafusp Alfa
• Hypofractionated Radiation Therapy

Trial Overview The trial tests a combination of hypofractionated radiation therapy (higher doses over a short period) and bintrafusp alfa (an immunotherapy drug). It aims to find the best dose and see how well this combo works against advanced intrahepatic cholangiocarcinoma by helping the immune system attack cancer.

Participant Groups

Group I: Treatment (hypofractionated radiation, bintrafusp alfa) Experimental Treatment 3 Interventions

Patients undergo hypofractionated radiation therapy QD on weekdays (Monday-Friday) for 15 fractions in the absence of disease progression or unacceptable toxicity. Beginning 1 week after completion of radiation therapy, patients receive bintrafusp alfa IV over 1 hour on day 1. Cycles repeat every 14 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Bintrafusp Alfa is already approved in United States, European Union for the following indications:

Approved in United States as Bintrafusp Alfa for:

• Non-small cell lung cancer (NSCLC)

Approved in European Union as Bintrafusp Alfa for:

• Biliary tract cancer

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

In a phase II study involving 111 high-risk prostate cancer patients, hypofractionated radiation therapy (HFRT) was found to be well tolerated, with no significant difference in acute gastrointestinal (GI) or genitourinary (GU) toxicity compared to conventionally fractionated radiation therapy (CFRT).

Both HFRT and CFRT resulted in similar 3-year biochemical recurrence-free survival rates (97.3% for HFRT vs 91.0% for CFRT) and overall survival rates (94.8% for HFRT vs 100.0% for CFRT), indicating that HFRT is a safe and effective treatment option for high-risk prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Outcomes of the CHIRP Trial: A Phase II Prospective Randomized Trial of Conventionally Fractionated Versus Moderately Hypofractionated Prostate and Pelvic Nodal Radiation Therapy in Patients With High-Risk Prostate Cancer. Wang, MH., Vos, LJ., Yee, D., et al.[2021]

The study demonstrated that hypofractionated, conformal radiation therapy (RT) at a dose of 50 Gy in 10 fractions is feasible and safe for treating patients with liver metastases, with no dose-limiting toxicities observed across all dose levels in a cohort of 26 patients.

While some patients experienced grade 3 toxicities, such as enteritis and lymphopenia, these were manageable and reversible, indicating that higher doses of radiation can be administered safely in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NRG Oncology/RTOG 0438: A Phase 1 Trial of Highly Conformal Radiation Therapy for Liver Metastases. Dawson, LA., Winter, KA., Katz, AW., et al.[2020]

The FORCE study is a phase II trial involving 130 patients with stage IV non-squamous non-small cell lung cancer, investigating the effects of nivolumab combined with hypofractionated palliative radiotherapy, aiming to assess its safety and efficacy in improving response rates and survival outcomes.

Preliminary data suggest that combining nivolumab with radiation therapy may enhance immune responses against tumors, potentially leading to better treatment outcomes compared to nivolumab alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fostering efficacy of anti-PD-1-treatment: Nivolumab plus radiotherapy in advanced non-small cell lung cancer - study protocol of the FORCE trial. Bozorgmehr, F., Hommertgen, A., Krisam, J., et al.[2020]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

Do Biliary Complications after Hypofractionated Radiation Therapy in Hepatocellular Carcinoma Matter? [2022]

2. China pubmed.ncbi.nlm.nih.gov

[Helical tomotherapy using simultaneously integrated boost and simultaneous integrated protection technique for unresectable biliary tract cancer]. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Phase I study of bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with pretreated biliary tract cancer. [2023]

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

Phase 2 trial of bintrafusp alfa as second-line therapy for patients with locally advanced/metastatic biliary tract cancers. [2023]

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

Hypofractionated Radiation Therapy for Unresectable/Locally Recurrent Intrahepatic Cholangiocarcinoma. [2021]

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

Clinical Outcomes of the CHIRP Trial: A Phase II Prospective Randomized Trial of Conventionally Fractionated Versus Moderately Hypofractionated Prostate and Pelvic Nodal Radiation Therapy in Patients With High-Risk Prostate Cancer. [2021]

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

NRG Oncology/RTOG 0438: A Phase 1 Trial of Highly Conformal Radiation Therapy for Liver Metastases. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Fostering efficacy of anti-PD-1-treatment: Nivolumab plus radiotherapy in advanced non-small cell lung cancer - study protocol of the FORCE trial. [2020]