Study of Pembrolizumab and Olaparib in Bile Duct Cancer

NCT04306367 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: STUDY00000908
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cholangiocarcinoma

Keywords

Cholangiocarcinoma

Outcome Measures

Primary Outcomes (1)

• 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.

  up to 2 years

Secondary Outcomes (4)

• Duration of Response

  3 years

• Progression Free Survival (PFS)

  3 years

• Overall Survival (OS)

  3 years

• Safety and Tolerability

  1 year

Study Arms (1)

Experimental

EXPERIMENTAL

Pembrolizumab Q3W, IV infusion (day 1 of each 3 week cycle) Olaparib bid, Oral tablet continuously

Drug: Pembrolizumab; Drug: Olaparib

Interventions

Pembrolizumab DRUG

200 mg given intravenously.

Also known as: Keytruda

Experimental

Olaparib DRUG

300 mg given orally.

Also known as: LYNPARZA

Experimental

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Georgetown University: lead

Study Sites (1)

Lombardi Comprehensive Cancer Center, Georgetown University

Washington D.C., District of Columbia, 20007, United States

Location

Related Publications (1)

• 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.

  PMID: 40629097 DERIVED

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

pembrolizumab; olaparib

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Aiwu Ruth He, MD
• Organization: Lombardi Comprehensive Cancer Center

Aiwu.R.He@gunet.georgetown.edu

202-444-2223

Study Officials

• John Marshall, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: February 11, 2020
• First Posted: March 12, 2020
• Study Start: April 1, 2020
• Primary Completion: July 16, 2023
• Study Completion: December 19, 2024
• Last Updated: February 17, 2025
• Results First Posted: December 17, 2024

Record last verified: 2025-02

Locations

US (1)