Trial 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)
NCT ID:
NCT06441747
Condition:
Cholangiocarcinoma
Conditions: Official terms:
Cholangiocarcinoma
Durvalumab
Olaparib
Conditions: Keywords:
Advanced Cholangiocarcinoma
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Durvalumab
Description:
Durvalumab will be administered at a dose of 1500mg intravenously every 4 weeks.
Arm group label:
Durvalumab and Olaparib
Other name:
Imfinzi
Intervention type:
Drug
Intervention name:
Olaparib
Description:
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.
Arm group label:
Durvalumab and Olaparib
Other name:
Lynparza
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.
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).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age ≥18 years, and life expectancy>12 weeks
2. Weight: >30kg
3. Histologically proven locally advanced or metastatic/unresectable cholangiocarcinoma
4. Documentation of RECISTv1.1 measurable disease
5. Must not have had radiologic progression after 6-8 cycles of gemcitabine and
cisplatin and durvalumab
6. Adequate haematological and end-organ function as defined by the following
parameters:
1. Haemoglobin ≥ 90g/L (without a transfusion in the past two weeks)
2. Platelets ≥100 x 109/L (without a transfusion in the past two weeks)
3. Neutrophils ≥ 1.0 x 109/L (without the use of G-CSF in the 4 weeks prior to
first dose)
4. ALT/AST <3x ULN irrespective of presence of liver metastases
5. Serum bilirubin ≤ 1.5x ULN except in cases of known Gilbert's Syndrome where
total bilirubin must be <4x ULN
6. Albumin ≥ 25 g/L
7. Serum Creatinine ≤1.5 x ULN or eGFR ≥ 30mL/min/1.73m2 as calculated by
Cockcroft Gault Equation
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
Exclusion Criteria:
1. Previous use of a PARP inhibitor.
2. 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.
3. 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.
4. Patients with severe chronic or active infections requiring systemic antibiotics or
antifungals in the two weeks prior to starting trial treatment.
5. Any of the following cardiovascular risk factors:
1. Acute myocardial infarction (MI) ≤6 months prior to study registration
2. New York Heart Association (NYHA) Heart Failure Class III-IV within ≤6 months
of registration
3. History of cerebral vascular accident (CVA) within 6 months of first dose
6. 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.
7. 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.
8. 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.
9. History of allogeneic organ transplantation.
10. 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:
1. Patients with vitiligo or alopecia.
2. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
hormone replacement.
3. Any chronic skin condition that does not require systemic therapy.
4. Patients without active disease in the last 5 years may be included but only
after consultation with the study physician.
5. Patients with celiac disease controlled by diet alone.
11. 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.
12. History of another primary malignancy except for:
1. 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.
2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease.
3. Adequately treated carcinoma in situ without evidence of disease.
13. 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).
14. History of active primary immunodeficiency.
15. 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.
1. 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
2. HCV positive (presence of anti-HCV antibodies); OR
3. HDV positive (presence of anti-HDV antibodies).
16. 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.
17. Current or prior use of immunosuppressive medication within 14 days before the first
dose of durvalumab. The following are exceptions to this criterion:
1. Intranasal, inhaled, topical steroids, or local steroid injections (e.g.,
intra-articular injection)
2. Systemic corticosteroids at physiologic doses that do not exceed 10 mg/day of
prednisolone or its equivalent.
3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication)
18. 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Chris O'Brien Lifehouse
Address:
City:
Camperdown
Zip:
2050
Country:
Australia
Contact:
Last name:
Sara Wahlroos
Phone:
0285140362
Email:
sara.wahlroos@lh.org.au
Investigator:
Last name:
Sara Wahlroos
Email:
Principal Investigator
Facility:
Name:
Monash Medical Centre
Address:
City:
Clayton
Zip:
3168
Country:
Australia
Contact:
Last name:
Marion Harris
Phone:
0385722392
Email:
marion.harris@monashhealth.org
Investigator:
Last name:
Marion Harris
Email:
Principal Investigator
Facility:
Name:
Westmead Hospital
Address:
City:
Westmead
Zip:
2145
Country:
Australia
Contact:
Last name:
Adnan Nagrial
Phone:
0403170371
Email:
Adnan.Nagrial@health.nsw.gov.au
Investigator:
Last name:
Adnan Nagrial
Email:
Principal Investigator
Facility:
Name:
Wollongong Hospital
Address:
City:
Wollongong
Zip:
2500
Country:
Australia
Contact:
Last name:
Lorraine Chantrill
Phone:
0242225260
Email:
Lorraine.chantrill@health.nsw.gov.au
Investigator:
Last name:
Lorraine Chantrill
Email:
Principal Investigator
Facility:
Name:
Royal Brisbane Women's Hospital
Address:
City:
Brisbane
Zip:
4006
Country:
Australia
Contact:
Last name:
Matthew Burge
Phone:
(07) 3636 8111
Email:
Matthew.Burge@health.qld.gov.au
Investigator:
Last name:
Matthew Burge
Email:
Principal Investigator
Facility:
Name:
Princess Alexandra Hospital
Address:
City:
Woolloongabba
Zip:
4102
Country:
Australia
Contact:
Last name:
Laura Tam
Investigator:
Last name:
Laura Tam
Email:
Principal Investigator
Facility:
Name:
Flinders Medical Centre
Address:
City:
Bedford Park
Country:
Australia
Contact:
Last name:
Amitesh Roy, Dr
Email:
amitesh.roy@sa.gov.au
Investigator:
Last name:
Amitesh Roy
Email:
Principal Investigator
Facility:
Name:
Austin Health
Address:
City:
Melbourne
Zip:
3084
Country:
Australia
Contact:
Last name:
Niall Tebbutt
Phone:
0394965763
Email:
niall.tebbutt@austin.org.au
Investigator:
Last name:
Niall Tebbutt
Email:
Principal Investigator
Facility:
Name:
Western Health
Address:
City:
Saint Albans
Zip:
3021
Country:
Australia
Contact:
Last name:
Lara Lipton
Phone:
0383456537
Email:
lara.lipton@mh.org.au
Investigator:
Last name:
Lara Lipton
Email:
Principal Investigator
Facility:
Name:
St John of God Hospital, Subiaco
Address:
City:
Perth
Country:
Australia
Contact:
Last name:
Andrew Dean
Phone:
0864659200
Email:
adean747@mac.com
Investigator:
Last name:
Andrew Dean
Email:
Principal Investigator
Start date:
August 2024
Completion date:
August 2028
Lead sponsor:
Agency:
Australasian Gastro-Intestinal Trials Group
Agency class:
Other
Collaborator:
Agency:
Wayne Elphinstone Research Fund
Agency class:
Other
Collaborator:
Agency:
AstraZeneca
Agency class:
Industry
Source:
Australasian Gastro-Intestinal Trials Group
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06441747
