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)

NCT06441747 | Recruiting Phase 2

• 1 other identifier: BIL-PPP
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 8

Brief 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.

Conditions

Cholangiocarcinoma

Keywords

Advanced Cholangiocarcinoma

Outcome Measures

Primary Outcomes (2)

• Primary Objective

  To describe the efficacy of PARPi and PDL1 inhibition in the maintenance setting of metastatic cholangiocarcinomas.

  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).

  12 months post randomisation

Secondary Outcomes (3)

• Evaluate toxicity

  12 months post randomisation

• Progression free survival

  12 months post randomisation

• Overall survival

  12 months post randomisation

Study Arms (1)

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.

Drug: Durvalumab; Drug: Olaparib

Interventions

Olaparib DRUG

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.

Also known as: Lynparza

Durvalumab and Olaparib

Durvalumab DRUG

Durvalumab will be administered at a dose of 1500mg intravenously every 4 weeks.

Also known as: Imfinzi

Durvalumab and Olaparib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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.
• i. Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
• ii. 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.
• 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:
• 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.

Sponsors & Collaborators

• Australasian Gastro-Intestinal Trials Group: lead
• Wayne Elphinstone Research Fund: collaborator
• AstraZeneca: collaborator

Study Sites (8)

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

RECRUITING

Monash Medical Centre

Clayton, New South Wales, 3168, Australia

RECRUITING

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

RECRUITING

Westmead Hospital

Westmead, New South Wales, 2145, Australia

RECRUITING

Wollongong and Shoalhaven District Memorial Hospital

Wollongong, New South Wales, 2500, Australia

NOT YET RECRUITING

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

RECRUITING

Flinders Medical Centre

Bedford Park, South Australia, Australia

RECRUITING

Austin Health

Melbourne, Victoria, 3084, Australia

RECRUITING

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

durvalumab; olaparib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Central Study Contacts

Clinical Project Manager

CONTACT

03 9496 3088; bil.ppp@onjcri.org.au

Sandra Bahamad

CONTACT

+61 7208 2714; Sandra@gicancer.org.au

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2024
• First Posted: June 4, 2024
• Study Start: September 23, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2028
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

AU (8)