Durvalumab + Chemotherapy for Biliary Tract Cancer

(TOPAZ-1 Trial)

Not currently recruiting at 148 trial locations
AC
AC
Overseen ByAstraZeneca Clinical Study Information Center
Age: 18+
Sex: Any
Trial Phase: Phase 3
Sponsor: AstraZeneca
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with advanced biliary tract cancer, including cancers of the bile ducts and gallbladder. The researchers aim to determine if adding Durvalumab (an immunotherapy) to standard chemotherapy (Gemcitabine and Cisplatin) is more effective than chemotherapy alone. Participants will receive either the Durvalumab combination or a placebo with the chemotherapy. The trial seeks individuals with advanced or metastatic biliary tract cancer that cannot be surgically removed and who have not received prior treatment for it. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that durvalumab, when combined with gemcitabine and cisplatin, is generally well-tolerated by patients. One study found that this combination helped patients with advanced biliary tract cancer live longer compared to standard chemotherapy alone. Previous studies on durvalumab have demonstrated that its side effects are manageable, with no unexpected reactions.

Earlier research indicated that patients taking durvalumab experienced side effects similar to those from other treatments in its category, such as fatigue, nausea, and reduced appetite. Serious side effects were rare. Notably, durvalumab is already approved for treating other types of cancer, indicating that its safety profile is well understood.

Overall, these findings suggest that combining durvalumab with chemotherapy offers a promising and relatively safe option for treating advanced biliary tract cancer.12345

Why do researchers think this study treatment might be promising for biliary tract cancer?

Researchers are excited about Durvalumab for biliary tract cancer because it works differently from standard treatments. While traditional therapies like gemcitabine and cisplatin focus on killing cancer cells directly, Durvalumab is an immunotherapy that helps the immune system recognize and attack cancer cells. This unique approach could potentially enhance the body's natural defenses to fight the cancer more effectively and with fewer side effects than conventional chemotherapy alone.

What evidence suggests that this trial's treatments could be effective for biliary tract cancer?

In this trial, participants will receive either durvalumab or a placebo alongside the usual chemotherapy drugs, gemcitabine and cisplatin. Research has shown that adding durvalumab to gemcitabine and cisplatin can greatly benefit people with advanced biliary tract cancer. Studies have found that this combination can help patients live longer and delay the progression of their cancer. Specifically, one study showed that fewer patients died when treated with durvalumab compared to those who received a placebo. These findings suggest that using durvalumab with chemotherapy might be more effective than chemotherapy alone for treating this type of cancer.14567

Who Is on the Research Team?

GC

Gordon Cohen

Principal Investigator

AstraZeneca

Are You a Good Fit for This Trial?

This trial is for adults with advanced biliary tract cancer, including cholangiocarcinoma and gallbladder carcinoma. They should be in good physical condition (WHO/ECOG PS of 0 or 1) and have not been treated before if their disease was inoperable or metastatic at diagnosis. Those who had surgery or adjuvant therapy must have completed it over six months ago.

Inclusion Criteria

I am fully active or can carry out light work.
My disease was advanced or spread to other parts when first diagnosed and hasn't been treated yet.
My cancer is in the bile ducts or gallbladder and cannot be surgically removed.
See 1 more

Exclusion Criteria

I have cancer that has spread to my brain or spinal cord.
I haven't had major surgery in the last 28 days.
I have had another type of cancer in the past.
See 2 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Durvalumab or Placebo in combination with Gemcitabine and Cisplatin

24 weeks
Tumor assessments every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

27 months
Tumor assessments every 8 weeks after the first 24 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • Durvalumab
  • Placebo
Trial Overview The study tests Durvalumab (an immunotherapy drug) combined with Gemcitabine/Cisplatin chemotherapy versus a placebo plus the same chemotherapy in patients facing their first line of treatment for advanced biliary tract cancer.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Treatment ArmExperimental Treatment1 Intervention
Group II: Placebo ArmPlacebo Group1 Intervention

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

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Approved in European Union as Imfinzi for:
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Approved in United States as Imfinzi for:
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Approved in Japan as Imfinzi for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials
4,491
Recruited
290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Citations

Durvalumab: A Review in Advanced Biliary Tract CancerIn the pivotal phase 3 TOPAZ-1 trial, durvalumab plus gemcitabine and cisplatin significantly prolonged overall survival and progression-free ...
Durvalumab for the Treatment of Advanced Biliary Tract ...Results showed a significant improvement in overall survival and progression-free survival with the combination therapy. After 41 months, the ...
NCT03046862 | Durvalumab(MEDI4736)/Tremelimumab in ...The combination of Durvalumab/Tremelimumab with gemcitabine/cisplatin chemotherapy is feasible and efficacious in chemo-naïve biliary tract cancer.
Durvalumab plus Gemcitabine and Cisplatin in Advanced ...As of data cutoff, 198 patients (58.1%) in the durvalumab group and 226 patients (65.7%) in the placebo group had died. Overall survival was ...
Evaluating the Therapeutic Potential of Durvalumab in ...Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer: an early exploratory analysis of real-world data. Liver Int ...
A Phase I, Open-Label, Multicentre Study to Evaluate the ...This is a phase I, open-label, multicentre study of MEDI4736 administered intravenously with a standard 3+3 dose-escalation phase to evaluate safety, ...
Phase I/II clinical trial of regorafenib plus durvalumab ...The hazard ratio for progression-free survival favored durvalumab at 0.75 (95% CI, 0.63 to 0.89; P=0.001). Objective response rates also showed improvement, ...
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