CholangiocarcinomaPhase 2NCT04306367
Study of Pembrolizumab and Olaparib in Bile Duct Cancer
A Phase 2 study testing Pembrolizumab and Olaparib in people with Cholangiocarcinoma, run by Georgetown University at 1 site in United States.
Trial summary
The investigators propose an open label, one-arm study to assess the safety and efficacy of olaparib and pembrolizumab in patients with cholangiocarcinoma who have progressed on or cannot tolerate gemcitabine-based therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cholangiocarcinoma
- What is being tested?
- Pembrolizumab 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
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Apr 2020to 19 Dec 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Be willing and able to provide written informed consent/assent for the trial.
- Be ≥ 18 years of age on day of signing informed consent.
- Patients must have received 1 line of prior systemic therapy for metastatic or resectable disease (i.e. patients may have received adjuvant gemcitabine and then later platin-based therapy for recurrent metastatic disease)
- Histological confirmation of cholangiocarcinoma manifesting as either intrahepatic, extrahepatic or gallbladder cancer. Patients with ampullary cancer are excluded.
- Have measurable disease based on RECIST 1.1.
- Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the sponsor-investigator. Subjects from whom a biopsy is not medically possible or safe may be enrolled on the study upon agreement from the principal investigator.
Show all 16Show fewer
- Have a performance status of 0 or 1 on the ECOG Performance Scale.
- Demonstrate adequate organ function as defined in Table 1. All screening labs will be performed within 28 days of registration.
- Table 1: Adequate Organ Function Laboratory Values System Laboratory Value Hematological Absolute neutrophil count (ANC) ≥ 1,500 /μL Platelets ≥ 100,000 / μL Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment) Renal Serum creatinine OR Measured or calculateda creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤ 1.5 X upper limit of normal (ULN) OR
- ≥ 50 mL/min for subject with creatinine levels > 1.5 x institutional ULN Hepatic Serum total bilirubin ≤ 2.0 X ULN AST (SGOT) and ALT (SGPT) ≤ 3.0 X ULN OR
- ≤ 5 X ULN for subjects with liver metastases Albumin > 2.5 mg/dL Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT)
- Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- ≤ 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants aCreatinine clearance should be calculated per institutional standard.
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section in Appendix 3). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
- Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
Who cannot join
- A history of anaphylaxis to olaparib
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- A woman of childbearing potential (WOCBP) who has a positive urine pregnancy test within 72 hours prior to 1st dose of treatment (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Has a known history of active TB (Bacillus Tuberculosis).
- Has known hypersensitivity to pembrolizumab or any of its excipients.
- Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
Show all 21Show fewer
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
- NOTE: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
- NOTE: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Has known history of, or any evidence of active, non-infectious pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the site investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
- Has known active Hepatitis B without HBV treatment (HBV infection with ongoing HBV treatment is allowed); chronic Hepatitis C infection is allowed. Any patient receiving treatment for HCV should wait at least 14 days after completion of HCV treatment before beginning study treatment. No patient should receive HCV treatment while receiving study treatment. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
- Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Lombardi Comprehensive Cancer Center, Georgetown University
Washington D.C., District of Columbia, 20007
About this study
Official title: A Phase II, Single-arm Study of Combination Pembrolizumab and Olaparib in the Treatment of Patients With Advanced Cholangiocarcinoma
The investigators propose an open label, one-arm study to assess the safety and efficacy of olaparib and pembrolizumab in patients with cholangiocarcinoma who have progressed on or cannot tolerate gemcitabine-based therapy.
Read the detailed description
The primary objective of the study is to assess the ORR of patients with advanced cholangiocarcinoma receiving a combination of pembrolizumab and olaparib. It is hypothesized that the addition of olaparib will improve the response rate of second line systemic therapy from 17.5% to 35% in patients with advanced cholangiocarcinoma.
The study is designed to enroll 33 subjects (for 85% power) with advanced stage cholangiocarcinoma to test the hypothesis that the combination of olaparib and pembrolizumab will increase the ORR in comparison with the ORR from second line systemic chemotherapy (historical control) in this patient population. As the primary study endpoint, which is also being used to determine the sample size of the study, the investigators propose that the combination of olaparib and pembrolizumab will increase the ORR to 35% from 17.5% (achieved with systemic cytotoxic chemotherapy including mFOLFOX-historical control). To allow a 10% patient drop off rate, the investigators expect to enroll a total of 36 subjects into this study. In addition, as secondary study endpoints the investigators expect to see an increase in the PFS and OS of patients receiving combination therapy compared to cytotoxic chemotherapy.
In this study, the investigators propose the collection of three biopsies-one at baseline prior to the start of treatment, one at the beginning of week 4, three weeks after the administration of combination olaparib and pembrolizumab, and one at the time of cancer progression-for the elucidation of exploratory study endpoints. Patients will have a CT or MRI scan at the beginning of treatment and then every 6 weeks thereafter for the first six months of study treatment administration, then every 9 weeks for up to 12 months after the start of treatment, followed by every 12 weeks up to 24 months on study. All patients will continue to receive olaparib and pembrolizumab combination treatment as tolerated unless unacceptable toxicities or cancer progression occur, at which time therapy will cease. In the absence of any problems, the planned study duration is 20-36 months.
- Conditions
- Cholangiocarcinoma
- Being tested
- Pembrolizumab, Olaparib
- Keywords
- Cholangiocarcinoma
- Medical subject headings
- Cholangiocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called Keytruda
200 mg given intravenously.
OlaparibDrug
Also called LYNPARZA
300 mg given orally.
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | Pembrolizumab Q3W, IV infusion (day 1 of each 3 week cycle)
Olaparib bid, Oral tablet continuously Receives: Drug: Pembrolizumab; Drug: Olaparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
The objective response rate (ORR) is the number of subjects with confirmed Partial Response or Complete Response according to RECIST 1.1, for target lesions assessed by Computed tomography (CT) Scan.
Measured: up to 2 years
Secondary outcomes (4)
Duration of Response
Duration of response (DOR), number of months from first response to progression.
Measured: 3 years
Progression Free Survival (PFS)
Progression free survival (PFS) is the time from enrollment to progression or death from any cause.
Measured: 3 years
Overall Survival (OS)
overall survival (OS) of subjects from the time of enrollment to death from any cause.
Measured: 3 years
Safety and Tolerability
Number of participants with a treatment-related adverse events as assessed by an Investigator according to CTCAE v4.0
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2020
- Study start1 Apr 2020
- Primary completion16 Jul 2023
- Study completion19 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CholangiocarcinomaStudies of the same condition, open and under way.
- More trials run by Georgetown UniversityThe sponsor's other registered studies.
- 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
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Georgetown University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- John Marshall, MD, Principal investigator, Georgetown University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04306367
- Sponsor's protocol ID
- STUDY00000908
- Status last verified
- Feb 2025
- First submitted
- 11 Feb 2020
- Last updated
- 17 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Sadagopan N, Wang H, Yin C, Weinberg BA, Noel MS, Mukherji R, Geng X, Marshall JL, He AR. A phase II single-arm study of combination pembrolizumab and olaparib in the treatment of patients with advanced biliary tract cancer. NPJ Precis Oncol. 2025 Jul 8;9(1):229. doi: 10.1038/s41698-025-01009-1.
PubMed 40629097
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Single-arm Study of Combination Pembrolizumab and Olaparib in the Treatment of Patients With Advanced Cholangiocarcinoma
- ClinicalTrials.gov ID
- NCT04306367
- Acronym / sponsor ID
- STUDY00000908
- Conditions
- Cholangiocarcinoma
- Keywords
- Cholangiocarcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Georgetown UniversityUniversity, hospital or other
- Study start
- 1 Apr 2020 (actual)
- Primary completion
- 16 Jul 2023 (actual)
- Study completion
- 19 Dec 2024 (actual)
- First posted
- 12 Mar 2020 (actual)
- Results
- Posted 17 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators propose an open label, one-arm study to assess the safety and efficacy of olaparib and pembrolizumab in patients with cholangiocarcinoma who have progressed on or cannot tolerate gemcitabine-based therapy.
Detailed description
The primary objective of the study is to assess the ORR of patients with advanced cholangiocarcinoma receiving a combination of pembrolizumab and olaparib. It is hypothesized that the addition of olaparib will improve the response rate of second line systemic therapy from 17.5% to 35% in patients with advanced cholangiocarcinoma.
The study is designed to enroll 33 subjects (for 85% power) with advanced stage cholangiocarcinoma to test the hypothesis that the combination of olaparib and pembrolizumab will increase the ORR in comparison with the ORR from second line systemic chemotherapy (historical control) in this patient population. As the primary study endpoint, which is also being used to determine the sample size of the study, the investigators propose that the combination of olaparib and pembrolizumab will increase the ORR to 35% from 17.5% (achieved with systemic cytotoxic chemotherapy including mFOLFOX-historical control). To allow a 10% patient drop off rate, the investigators expect to enroll a total of 36 subjects into this study. In addition, as secondary study endpoints the investigators expect to see an increase in the PFS and OS of patients receiving combination therapy compared to cytotoxic chemotherapy.
In this study, the investigators propose the collection of three biopsies-one at baseline prior to the start of treatment, one at the beginning of week 4, three weeks after the administration of combination olaparib and pembrolizumab, and one at the time of cancer progression-for the elucidation of exploratory study endpoints. Patients will have a CT or MRI scan at the beginning of treatment and then every 6 weeks thereafter for the first six months of study treatment administration, then every 9 weeks for up to 12 months after the start of treatment, followed by every 12 weeks up to 24 months on study. All patients will continue to receive olaparib and pembrolizumab combination treatment as tolerated unless unacceptable toxicities or cancer progression occur, at which time therapy will cease. In the absence of any problems, the planned study duration is 20-36 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Drug: Pembrolizumab, Drug: OlaparibPembrolizumab Q3W, IV infusion (day 1 of each 3 week cycle) Olaparib bid, Oral tablet continuously |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Be willing and able to provide written informed consent/assent for the trial.
- Be ≥ 18 years of age on day of signing informed consent.
- Patients must have received 1 line of prior systemic therapy for metastatic or resectable disease (i.e. patients may have received adjuvant gemcitabine and then later platin-based therapy for recurrent metastatic disease)
- Histological confirmation of cholangiocarcinoma manifesting as either intrahepatic, extrahepatic or gallbladder cancer. Patients with ampullary cancer are excluded.
- Have measurable disease based on RECIST 1.1.
Key exclusion criteria (21 listed)
- A history of anaphylaxis to olaparib
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- A woman of childbearing potential (WOCBP) who has a positive urine pregnancy test within 72 hours prior to 1st dose of treatment (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Has a known history of active TB (Bacillus Tuberculosis).
- Has known hypersensitivity to pembrolizumab or any of its excipients.
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 |
|---|---|---|
| PembrolizumabAlso: Keytruda200 mg given intravenously. | Drug | Experimental |
| OlaparibAlso: LYNPARZA300 mg given orally. | Drug | Experimental |
Primary outcome
Objective Response Rate (ORR)
Time frame: up to 2 years
The objective response rate (ORR) is the number of subjects with confirmed Partial Response or Complete Response according to RECIST 1.1, for target lesions assessed by Computed tomography (CT) Scan.
4 secondary outcomes
Duration of Response
Time frame: 3 years
Progression Free Survival (PFS)
Time frame: 3 years
Overall Survival (OS)
Time frame: 3 years
Safety and Tolerability
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40629097Sadagopan N, Wang H, Yin C, Weinberg BA, Noel MS, Mukherji R, Geng X, Marshall JL, He AR. A phase II single-arm study of combination pembrolizumab and olaparib in the treatment of patients with advanced biliary tract cancer. NPJ Precis Oncol. 2025 Jul 8;9(1):229. doi: 10.1038/s41698-025-01009-1.
Related trials for Cholangiocarcinoma
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
Active, not recruitingPhase 2/3
A Study of CTX-009 in Combination With Paclitaxel in Adult Patients With Unresectable Advanced, Metastatic or Recurrent Biliary Tract Cancers (COMPANION-002)
Biliary Tract Cancer, Cholangiocarcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Active, not recruitingObservational study
Liver Cancer Registry Platform
Hepatocellular Carcinoma (HCC), Cholangiocarcinoma
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. This study is not recruiting at the moment.
John Marshall, MD principal investigator
Georgetown University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab and Olaparib in people with Cholangiocarcinoma, run by Georgetown University at 1 site in United States.
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 16 inclusion and 21 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: finished, as of the sponsor's last update on 17 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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?
Yes. Results are posted in the registry (first posted 17 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: up to 2 years). 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 NCT04306367, 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 17 Feb 2025; AzTrials last refreshed its copy on 8 Nov 2026.