Actively Recruiting

Phase 2
Age: 19Years +
All Genders
NCT05222971

Olaparib With or Without Durvalumab for DDR Gene Mutated Biliary Tract Cancer Following Platinum-based Chemotherapy

Led by Asan Medical Center · Updated on 2025-01-28

62

Participants Needed

1

Research Sites

247 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

First-line gemcitabine plus cisplatin chemotherapy is the standard first-line treatment for unresectable or metastatic advanced biliary tract cancer and the optimal duration of the treatment is not mentioned in current clinical guidelines. In the pivotal phase 3 ABC-02 trial, patients received up to 6 to 8 cycles of treatment and stopped without maintenance and our retrospective study shows no significant benefit of continuing gemcitabine plus cisplatin beyond 6 to 8 cycles. However, the survival outcomes of patients who completed 6 to 8 cycles of gemcitabine plus cisplatin without progression are dismal with progression-free survival from the last dose of the treatment of median 5.2 months in a prior retrospective study. Indeed, there is an unmet clinical need in terms of maintenance therapy for advanced biliary tract cancer without progression to first-line gemcitabine plus cisplatin chemotherapy. Durvalumab with/without tremelimumab, anti-CTLA4 inhibitor, showed encouraging results in recently presented study for treatment of advanced biliary tract cancer combination with gemcitabine plus cisplatin. Combination of olaparib and durvalumab showed promising results for metastatic HER-2 negative BRCA mutated breast cancer. For DDR gene mutated advanced biliary tract cancer, olaparib plus durvalumab combination may show synergistic effect with better efficacy than olaparib monotherapy. Both olaparib and durvalumab are relatively well tolerated compared to other cytotoxic chemotherapeutic agents. Olaparib may have some degree of myelosuppression, most patients are expected to well tolerate. Although combination of durvalumab and olaparib may cause additional adverse events, these also might be tolerable, considering that there are no overlapping toxicities between durvalumab and olaparib and the safety data for the combination of durvalumab with olaparib. Considering poor prognosis in patients with advanced biliary tract cancer and lack of maintenance treatment following scheduled first-line GemCis, clinical benefits with maintenance olaparib or olaparib plus durvalumab weigh more than the potential risks.

CONDITIONS

Official Title

Olaparib With or Without Durvalumab for DDR Gene Mutated Biliary Tract Cancer Following Platinum-based Chemotherapy

Who Can Participate

Age: 19Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Able to provide signed informed consent and comply with study requirements
  • Age 19 years or older
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Life expectancy of at least 16 weeks
  • Histologically confirmed adenocarcinoma of the biliary tract (intrahepatic, extrahepatic cholangiocarcinoma, or gallbladder carcinoma)
  • Locally advanced unresectable, recurrent after curative surgery, or metastatic disease
  • Completed at least 16 weeks of continuous first-line platinum-based chemotherapy for unresectable or metastatic disease
  • Confirmed somatic or germline mutation in at least one DNA damage repair gene by targeted exome sequencing
  • Measurable disease not required for enrollment
  • No active uncontrolled infection except chronic viral hepatitis under antiviral therapy
  • Normal organ and bone marrow function within 28 days prior to treatment including hemoglobin ≥10.0 g/dL with no recent blood transfusion, platelets ≥100 x 10^9/L, neutrophils ≥1.5 x 10^9/L, creatinine clearance ≥51 mL/min, serum total bilirubin ≤1.5 x ULN, and ALT/AST ≤2.5 x ULN
  • No other malignant disease except certain treated cancers without relapse for over 5 years
  • Body weight greater than 30 kg
  • Willing and able to comply with the study protocol, including treatment and scheduled visits
Not Eligible

You will not qualify if you...

  • Participation in another clinical study with an investigational product within the last 6 months
  • Concurrent enrollment in another clinical study except observational or follow-up periods
  • Medical or psychiatric conditions affecting consent or protocol compliance
  • Use of strong or moderate CYP3A inhibitors or inducers without required washout periods
  • Obstruction of the gastrointestinal tract or active gastrointestinal bleeding
  • Recent myocardial infarction (within 6 months) or significant heart disease
  • Severe or uncontrolled systemic disease or conditions making participation undesirable
  • Combined hepatocellular carcinoma/cholangiocarcinoma
  • ECG abnormalities including QTcF ≥470 ms or uncontrolled cardiac conditions
  • Diagnosis or features of myelodysplastic syndrome/acute myeloid leukemia
  • Presence of leptomeningeal carcinomatosis or symptomatic uncontrolled brain metastases
  • Inability to swallow oral medication or gastrointestinal disorders interfering with absorption
  • Unresolved toxicity grade 2 or higher from prior anticancer therapy except alopecia and vitiligo
  • Major surgery within 28 days prior to first dose (except local palliative surgery)
  • History of allogenic organ or double umbilical cord blood transplantation
  • Active or prior autoimmune or inflammatory disorders
  • History of active primary immunodeficiency
  • Active infections including tuberculosis, hepatitis B or C
  • Use of immunosuppressive medication within 14 days before first durvalumab dose
  • Receipt of live attenuated vaccine within 30 days prior to first dose
  • Pregnancy or breastfeeding, or unwillingness to use effective birth control during and after treatment
  • Concomitant use of strong or moderate CYP3A inhibitors/inducers without adequate washout before olaparib

AI-Screening

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Trial Site Locations

Total: 1 location

1

Asan Medical Center

Seoul, South Korea, 05505

Actively Recruiting

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Research Team

C

Changhoon Yoo

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

2

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