Olaparib in Treating Patients With Metastatic Biliary Tract Cancer With Aberrant DNA Repair Gene Mutations

• Register: ClinicalTrials.gov
• Last refreshed on: 23 October 2023
• Main ID: NCT04042831
• Date of registration: 29/07/2019
• Prospective Registration: Yes
• Primary sponsor: Academic and Community Cancer Research United
• Public title: Olaparib in Treating Patients With Metastatic Biliary Tract Cancer With Aberrant DNA Repair Gene Mutations
• Scientific title: A Phase II Study of Olaparib in Patients With Advanced Biliary Tract Cancer With Aberrant DNA Repair Gene Mutations
• Date of first enrolment: June 24, 2020
• Target sample size: 36
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT04042831
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Daniel H Ahn
• Affiliation: Academic and Community Cancer Research United

Key inclusion & exclusion criteria

Inclusion Criteria:

- Age >= 18 years

- Histological or cytological documentation of metastatic adenocarcinoma of the biliary
tract

- Patients with previously identified genetic aberrations that are associated with
homologous recombinant repair pathway will be eligible [e.g. somatic mutations in ATM,
ATR, CHEK2, BRCA 1/2, RAD51, BRIP1, PALB2, PTEN, FANC, NBN, EMSY, MRE11, ARID1A] or
germline mutations in the above genes. Clinical Laboratory Improvement Act
(CLIA)-certified assays including commercial tests (Foundation Medicine, Caris,
Tempus) will be allowed

- Measurable disease

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2. (Form is
available on the Academic and Community Cancer Research United [ACCRU] website)

- Life expectancy of >= 16 weeks per estimation of investigator

- Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 7 days prior to
registration)

- Platelet count >= 75,000/mm^3 (obtained =< 7 days prior to registration)

- Hemoglobin >= 9.0 g/dL with no blood transfusion in the past 28 days (obtained =< 7
days prior to registration)

- Total bilirubin =< 1.5 x upper limit of normal (ULN) (obtained =< 7 days prior to
registration)

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN (=< 5
x ULN for subjects with liver involvement of their cancer) (obtained =< 7 days prior
to registration)

- Serum creatinine =< 1.5 x ULN (obtained =< 7 days prior to registration)

- Institutional normalized ratio (INR)/activated partial thromboplastin time (aPTT) =<
1.5 x ULN (obtained =< 7 days prior to registration)

- Exception: Patients who are therapeutically treated with anticoagulant agents
will be allowed to participate provided that no prior evidence of underlying
abnormality in coagulation parameters exists. Close monitoring of at least weekly
evaluations will be performed until INR/PTT is stable based on a measurement that
is pre-dose as defined by the local standard of care

- Alkaline phosphatase limit =< 2.5 x ULN (=< 5 x ULN for patients with liver
involvement of their cancer) (obtained =< 7 days prior to registration)

- Creatinine clearance estimated of >= 51 mL/min using the Cockcroft-Gault equation
(obtained =< 7 days prior to registration)

- Negative serum pregnancy test done =< 28 days prior to registration and confirmed
prior to treatment on day 1, for women of childbearing potential, postmenopausal women
or women of childbearing potential with evidence of non-childbearing status.

- Postmenopausal is defined as:

- Amenorrheic for 1 year or more following cessation of exogenous hormonal
treatments

- Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in
the post-menopausal range for women under 50

- Radiation-induced oophorectomy with last menses > 1 year ago

- Chemotherapy-induced menopause with > 1 year interval since last menses

- Surgical sterilization (bilateral oophorectomy or hysterectomy)

- Provide informed written consent

- Willing to return to enrolling institution for follow-up (during the active monitoring
phase of the study)

- Willing to provide blood and tissue for correlative purposes

- Hepatitis B virus surface antigen (HBsAg), anti-hepatitis B virus core antigen
(anti-HBc) and hepatitis B virus surface antigen (anti-HBs)

- Patients with chronic HBV receiving any systemic anticancer therapy should receive
antiviral prophylactic therapy through and for minimum 12 months following anticancer
therapy

- Patients with past HBV undergoing other systemic anticancer therapies not clearly
associated with a high risk of HBV reactivation should be monitored with HBsAg and
alanine aminotransferase during cancer treatment (suggest every other cycle)

Exclusion Criteria:

- Platinum refractory disease which was defined as:

- Evidence disease progression on platinum based chemotherapy regimen or

- Evidence of disease progression =< 6 months of completion of platinum based
adjuvant chemotherapy regimen

- Patient has received prior systemic anti-cancer therapy, tumor embolization or
radiotherapy =< 28 days prior to registration

- Major surgical procedure, open biopsy, or significant traumatic injury =< 28 days
prior to registration

- NOTE: Patients must have recovered from any effects of any major surgery

- Congestive heart failure - New York Heart Association (NYHA) >= class II

- Resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible
cardiac conditions, as judged by the investigator (eg. unstable ischemia, uncontrolled
symptomatic arrhythmia, corrected QT interval by Fridericia's correction formula
[QTcF] prolongation > 500 ms, electrolyte disturbances, etc.), or patients with
congenital long QT syndrome. Cardiac arrhythmias requiring anti-arrhythmic therapy.

- NOTE: Pacemaker, beta blockers or digoxin are permitted

- Uncontrolled hypertension - grade 3 or higher per Common Terminology Criteria for
Adverse Events (CTCAE) version (v) 5.0. (despite optimal medical management)

- History of or current pheochromocytoma

- Arterial or venous thrombotic or embolic events such as cerebrovascular accident
(including transient ischemic attacks), deep vein thrombosis or pulmonary embolism =<
6 months prior to registration

- Ongoing infection > grade 2 National Cancer Institute (NCI)-Common Terminology
Criteria for Adverse Events (CTCAE) version (v)5.0

- Seizure disorder requiring medication

- Symptomatic metastatic brain or meningeal tumors unless the patient is > 6 months from
definitive therapy, has a negative imaging study =< 28 days of registration and is
clinically stable with respect to the tumor at the time of registration. Patients with
spinal cord compression unless considered to have received definitive treatment for
this and evidence of clinically stable disease for 28 days prior to registration

- NOTE: The patient can receive a stable dose of corticosteroids before and during
the study as long as these were started =< 28 days prior to registration

- History of organ allograft (including corneal transplant) or allogenic bone marrow
transplant or double umbilical cord blood transplantation (dUCBT)




Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Metastatic Bile Duct Carcinoma

Fanconi Anemia Complementation Group Gene Mutation

PTEN Gene Deletion

Bile Duct Adenocarcinoma

Intervention(s)

Procedure: Biospecimen Collection

Procedure: Computed Tomography

Procedure: Magnetic Resonance Imaging

Drug: Olaparib

Primary Outcome(s)

Progression-free survival (PFS) at first scan [Time Frame: At first scan (approximately 8 weeks)]

Secondary Outcome(s)

PFS [Time Frame: From study entry to the first of either disease progression or death from any cause, assessed up to 3 years]

Duration of response (DoR) [Time Frame: Up to 3 years]

Incidence of adverse events [Time Frame: Up to 3 years]

Objective response rate [Time Frame: Up to 3 years]

Overall survival (OS) [Time Frame: From study entry to death from any cause, assessed up to 3 years]

Secondary ID(s)

NCI-2019-04434

ACCRU-ICRN-1702

P30CA015083

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Cancer Institute (NCI)