CholangiocarcinomaPhase 2NCT06441747
Phase II Study of the Combination of Durvalumab (MEDI4736) (PDL1 Inhibitor) and Olaparib (PARP Inhibitor) in Advanced Cholangiocarcinoma After Initial Chemotherapy and Durvalumab (BIL-PPP)
A Phase 2 study testing Durvalumab and Olaparib in people with Cholangiocarcinoma, run by Australasian Gastro-Intestinal Trials Group at 8 sites in Australia.
Trial summary
The aim of this study is to investigate whether the combination of durvalumab and olaparib in the maintenance setting after initial chemotherapy and durvalumab will benefit patients with locally advanced or metastatic cholangiocarcinoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cholangiocarcinoma
- What is being tested?
- Durvalumab and Olaparib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 8 sitesAustralia
- Study dates
- 23 Sep 2024to Aug 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years, and life expectancy>12 weeks
- Weight: >30kg
- Histologically proven locally advanced or metastatic/unresectable cholangiocarcinoma
- Documentation of RECISTv1.1 measurable disease
- Must not have had radiologic progression after 6-8 cycles of gemcitabine and cisplatin and durvalumab
- Adequate haematological and end-organ function as defined by the following parameters:
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- Haemoglobin ≥ 90g/L (without a transfusion in the past two weeks)
- Platelets ≥100 x 109/L (without a transfusion in the past two weeks)
- Neutrophils ≥ 1.0 x 109/L (without the use of G-CSF in the 4 weeks prior to first dose)
- ALT/AST <3x ULN irrespective of presence of liver metastases
- Serum bilirubin ≤ 1.5x ULN except in cases of known Gilbert's Syndrome where total bilirubin must be <4x ULN
- Albumin ≥ 25 g/L
- Serum Creatinine ≤1.5 x ULN or eGFR ≥ 30mL/min/1.73m2 as calculated by Cockcroft Gault Equation
- Able to swallow oral medications without any difficulties or medical history associated with malabsorption or any conditions that may impact on compliance or absorption of the study treatment.
- Women of Childbearing potential must be either totally abstinent or agree to use at least one highly effective method of birth control (e.g., oral contraceptive pill, barrier method) for the duration of the study and for at least 6 months after the final dose of study medication. They must also have a negative serum beta-hCG in the 7 days prior to first dose of study drug.
- Non-sterile males and their female partners must also either be totally abstinent or agree to use at least one highly effective method of birth control (e.g., oral contraceptive pill, barrier method) for the duration of the study and for at least 6 months after the final dose of study medication.
- Patient is willing and able to comply with the protocol for the duration of the study, including undergoing treatment and scheduled visits and examinations including follow up.
- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
Who cannot join
- Previous use of a PARP inhibitor.
- All prior treatment-related AEs must have resolved to a CTCAE v5 Grade 1 or less prior to commencement of study medication, with the exception of alopecia and peripheral neuropathy which can be grade 2 or less.
- Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
- Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or olaparib may be included only after consultation with the Study Chairs.
- Known symptomatic or progressive CNS metastases or leptomeningeal disease. Patients with treated brain metastases are eligible for inclusion in the study if they had received treatment >4 weeks prior to commencement of study medication, and have a repeat MRI scan demonstrating stability in disease.
- Patients with severe chronic or active infections requiring systemic antibiotics or antifungals in the two weeks prior to starting trial treatment.
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- Any of the following cardiovascular risk factors:
- Acute myocardial infarction (MI) ≤6 months prior to study registration
- New York Heart Association (NYHA) Heart Failure Class III-IV within ≤6 months of registration
- History of cerebral vascular accident (CVA) within 6 months of first dose
- Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study, or during the follow-up period of an interventional study.
- Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug.
- Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
- History of allogeneic organ transplantation.
- Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
- Patients with vitiligo or alopecia.
- Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement.
- Any chronic skin condition that does not require systemic therapy.
- Patients without active disease in the last 5 years may be included but only after consultation with the study physician.
- Patients with celiac disease controlled by diet alone.
- Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhoea, or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring AEs, or compromise the ability of the patient to give written informed consent.
- History of another primary malignancy except for:
- Malignancy treated with curative intent and with no known active disease ≥2 years before the first dose of IP and of low potential risk for recurrence.
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
- Adequately treated carcinoma in situ without evidence of disease.
- Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart).
- History of active primary immunodeficiency.
- Known active hepatitis infection, positive hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HBsAg) or HBV core antibody (anti-HBc), at screening. Participants with a past or resolved HBV infection (defined as the presence of anti HBc and absence of HBsAg) are eligible. Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
- Participants co-infected with HBV and HCV, or co-infected with HBV and HDV, namely: HBV positive (presence of HBsAg and/or anti HBcAb with detectable HBV DNA); AND
- HCV positive (presence of anti-HCV antibodies); OR
- HDV positive (presence of anti-HDV antibodies).
- Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies) or active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice). Known HIV infection that is not well controlled. All of the following criteria are required to define an HIV infection that is well controlled: undetectable viral RNA load for 6 months prior, CD4+ count of >500, no history of AIDS-defining opportunistic infection within the past 12 months, and stable for at least 6 months on the same anti-HIV medications.
- Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra-articular injection)
- Systemic corticosteroids at physiologic doses that do not exceed 10 mg/day of prednisolone or its equivalent.
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
- Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 90days after the last dose of IP.19. Female patients who are pregnant or breastfeeding, or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy.
- 20. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
- 21. Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements.
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
Australia8 sites, 8 recruiting
- Recruiting
Flinders Medical Centre
Bedford Park, South Australia
Amitesh Roy, 0882048997, amitesh.roy@sa.gov.au
Amitesh Roy
- Recruiting
Chris O'Brien Lifehouse
Camperdown, New South Wales, 2050
Sara Wahlroos, 0285140362, sara.wahlroos@lh.org.au
Sara Wahlroos
- Recruiting
Monash Medical Centre
Clayton, New South Wales, 3168
Marion Harris, 0385722392, marion.harris@monashhealth.org
Marion Harris
- Recruiting
Austin Health
Melbourne, Victoria, 3084
Niall Tebbutt, 0394965763, niall.tebbutt@austin.org.au
Niall Tebbutt
- Recruiting
Royal North Shore Hospital
St Leonards, New South Wales, 2065
Sally McCowatt, 02 9463 1181, sally.mccowatt@health.nsw.gov.au
- Recruiting
Westmead Hospital
Westmead, New South Wales, 2145
Adnan Nagrial, 0288905200, Adnan.Nagrial@health.nsw.gov.au
Adnan Nagrial
- Not yet recruiting
Wollongong and Shoalhaven District Memorial Hospital
Wollongong, New South Wales, 2500
Lorraine Chantrill, 0242225260, Lorraine.chantrill@health.nsw.gov.au
Lorraine Chantrill
- Recruiting
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102
Laura Tam, 0734438050, laura.tam@austin.org.au
Laura Tam
About this study
The aim of this study is to investigate whether the combination of durvalumab and olaparib in the maintenance setting after initial chemotherapy and durvalumab will benefit patients with locally advanced or metastatic cholangiocarcinoma.
Read the detailed description
The primary objectives are
(i) To describe the efficacy of PARPi and PDL1 inhibition in the maintenance setting of metastatic cholangiocarcinomas.
(ii) To refine selection of the patient population who are most likely to benefit from the combination of PDL1 (Durvalumab) and PARP (Olaparib) inhibition in the maintenance setting following initial chemotherapy (cisplatin + gemcitabine + Durvalumab) (post hoc translational analysis).
The secondary objectives are (i) To evaluate toxicity of the combination of durvalumab and olaparib. (ii) To evaluate progression-free and overall survival with the combination of durvalumab and olaparib (PFS, OS).
- Conditions
- Cholangiocarcinoma
- Being tested
- Durvalumab, Olaparib
- Keywords
- Advanced Cholangiocarcinoma
- Medical subject headings
- Cholangiocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabDrug
Also called Imfinzi
Durvalumab will be administered at a dose of 1500mg intravenously every 4 weeks.
OlaparibDrug
Also called Lynparza
Olaparib is administered at a dose of 300mg bd in a continuous 28-day cycle. On day 1 of each cycle, the morning dose of Olaparib should be taken no more than 1 hour prior to infusion of durvalumab. It is expected that patients will receive up to 24 months of a combination of olaparib and durvalumab, or until disease progression, unacceptable toxicities, or withdrawal of consent.
| Study group | Role | What they receive |
|---|---|---|
| Durvalumab and Olaparib | Experimental | This is a trial of Durvalumab in combination with olaparib. Durvalumab will be administered at a dose of 1500mg intravenously every 4 weeks. Olaparib will be administered orally at a dose of 300mg twice daily continuously. This combination will be administered for a maximum of two years unless unacceptable toxicities or progressive disease. Receives: Drug: Durvalumab; Drug: Olaparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Objective
To describe the efficacy of PARPi and PDL1 inhibition in the maintenance setting of metastatic cholangiocarcinomas.
Measured: 12 months post randomisation
Evaluate benefit
To refine selection of the patient population who are most likely to benefit from the combination of PDL1 (durvalumab) and PARP (olaparib) inhibition in the maintenance setting following initial chemotherapy (cisplatin + gemcitabine + durvalumab) (post hoc translational analysis).
Measured: 12 months post randomisation
Secondary outcomes (3)
Evaluate toxicity
To evaluate toxicity of the combination of durvalumab and olaparib.
Measured: 12 months post randomisation
Progression free survival
To evaluate progression-free survival with the combination of durvalumab and olaparib (PFS).
Measured: 12 months post randomisation
Overall survival
To evaluate overall survival with the combination of durvalumab and olaparib (OS).
Measured: 12 months post randomisation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2024
- Study start23 Sep 2024
- Primary completionAug 2026 (estimated)
- Study completionAug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CholangiocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Australasian Gastro-Intestinal Trials Group
- Sponsor type
- Research network
- Collaborators
- Wayne Elphinstone Research Fund, AstraZeneca
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06441747
- Sponsor's protocol ID
- BIL-PPP
- Status last verified
- May 2026
- First submitted
- 29 May 2024
- Last updated
- 6 May 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Nilsen O, Senko C, Collins A, Tomkins N, Buckley D, Weickhardt A, Tebbutt N. Triple M Syndrome Associated With Concurrent Durvalumab and Olaparib Therapy in Metastatic Cholangiocarcinoma: A Case Report. Case Rep Oncol Med. 2026 Jun 22;2026:1318038. doi: 10.1155/crom/1318038. eCollection 2026.
PubMed 42338513
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of the Combination of Durvalumab (MEDI4736) (PDL1 Inhibitor) and Olaparib (PARP Inhibitor) in Advanced Cholangiocarcinoma After Initial Chemotherapy and Durvalumab (BIL-PPP)
- ClinicalTrials.gov ID
- NCT06441747
- Acronym / sponsor ID
- BIL-PPP
- Conditions
- Cholangiocarcinoma
- Keywords
- Advanced Cholangiocarcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Australasian Gastro-Intestinal Trials GroupResearch network
- Collaborators
- Wayne Elphinstone Research Fund, AstraZeneca
- Study start
- 23 Sep 2024 (actual)
- Primary completion
- Aug 2026 (estimated)
- Study completion
- Aug 2028 (estimated)
- First posted
- 4 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this study is to investigate whether the combination of durvalumab and olaparib in the maintenance setting after initial chemotherapy and durvalumab will benefit patients with locally advanced or metastatic cholangiocarcinoma.
Detailed description
The primary objectives are
(i) To describe the efficacy of PARPi and PDL1 inhibition in the maintenance setting of metastatic cholangiocarcinomas.
(ii) To refine selection of the patient population who are most likely to benefit from the combination of PDL1 (Durvalumab) and PARP (Olaparib) inhibition in the maintenance setting following initial chemotherapy (cisplatin + gemcitabine + Durvalumab) (post hoc translational analysis).
The secondary objectives are (i) To evaluate toxicity of the combination of durvalumab and olaparib. (ii) To evaluate progression-free and overall survival with the combination of durvalumab and olaparib (PFS, OS).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Durvalumab and Olaparib | Experimental | Drug: Durvalumab, Drug: OlaparibThis is a trial of Durvalumab in combination with olaparib. Durvalumab will be administered at a dose of 1500mg intravenously every 4 weeks. Olaparib will be administered orally at a dose of 300mg twice daily continuously. This combination will be administered for a maximum of two years unless unacceptable toxicities or progressive disease. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Age ≥18 years, and life expectancy>12 weeks
- Weight: >30kg
- Histologically proven locally advanced or metastatic/unresectable cholangiocarcinoma
- Documentation of RECISTv1.1 measurable disease
- Must not have had radiologic progression after 6-8 cycles of gemcitabine and cisplatin and durvalumab
Key exclusion criteria (39 listed)
- Previous use of a PARP inhibitor.
- All prior treatment-related AEs must have resolved to a CTCAE v5 Grade 1 or less prior to commencement of study medication, with the exception of alopecia and peripheral neuropathy which can be grade 2 or less.
- Known symptomatic or progressive CNS metastases or leptomeningeal disease. Patients with treated brain metastases are eligible for inclusion in the study if they had received treatment >4 weeks prior to commencement of study medication, and have a repeat MRI scan demonstrating stability in disease.
- Patients with severe chronic or active infections requiring systemic antibiotics or antifungals in the two weeks prior to starting trial treatment.
- Any of the following cardiovascular risk factors:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DurvalumabAlso: ImfinziDurvalumab will be administered at a dose of 1500mg intravenously every 4 weeks. | Drug | Durvalumab and Olaparib |
| OlaparibAlso: LynparzaOlaparib is administered at a dose of 300mg bd in a continuous 28-day cycle. On day 1 of each cycle, the morning dose of Olaparib should be taken no more than 1 hour prior to infusion of durvalumab. It is expected that patients will receive up to 24 months of a combination of olaparib and durvalumab, or until disease progression, unacceptable toxicities, or withdrawal of consent. | Drug | Durvalumab and Olaparib |
Primary outcome
Primary Objective
Time frame: 12 months post randomisation
To describe the efficacy of PARPi and PDL1 inhibition in the maintenance setting of metastatic cholangiocarcinomas.
Evaluate benefit
Time frame: 12 months post randomisation
To refine selection of the patient population who are most likely to benefit from the combination of PDL1 (durvalumab) and PARP (olaparib) inhibition in the maintenance setting following initial chemotherapy (cisplatin + gemcitabine + durvalumab) (post hoc translational analysis).
3 secondary outcomes
Evaluate toxicity
Time frame: 12 months post randomisation
Progression free survival
Time frame: 12 months post randomisation
Overall survival
Time frame: 12 months post randomisation
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2026.
- Derived from this study: PubMed 42338513Nilsen O, Senko C, Collins A, Tomkins N, Buckley D, Weickhardt A, Tebbutt N. Triple M Syndrome Associated With Concurrent Durvalumab and Olaparib Therapy in Metastatic Cholangiocarcinoma: A Case Report. Case Rep Oncol Med. 2026 Jun 22;2026:1318038. doi: 10.1155/crom/1318038. eCollection 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Durvalumab and Olaparib in people with Cholangiocarcinoma, run by Australasian Gastro-Intestinal Trials Group at 8 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Clinical Project Manager (03 9496 3088, bil.ppp@onjcri.org.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Objective (time frame: 12 months post randomisation). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06441747, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2026.