AZD6738 Plus Durvalumab in Biliary Tract Cancer

NCT04298008 | Recruiting Phase 2

• 1 other identifier: BTC-IO RR
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

This trial will enroll advanced biliary tract cancer patients who have been previously treated with immunotherapy in either the 2nd or 3rd line. Patients will be treated with AZD6738 and Durvalumab combination.

Conditions

Bile Duct Cancer; Chemotherapy Effect

Outcome Measures

Primary Outcomes (1)

• disease control rate (DCR) of AZD6738 and Durvalumab combination

  Disease control rate based on RECIST v1.1

  through study completion, an average of 1 year

Secondary Outcomes (6)

• overall response rate (ORR) of AZD6738 and Durvalumab combination

  through study completion, an average of 1 year

• progression-free survival of AZD6738 and Durvalumab combination

  through study completion, an average of 1 year

• duration of response of AZD6738 and Durvalumab combination

  through study completion, an average of 1 year

• overall survival of AZD6738 and Durvalumab combination

  every 12 weeks until death or up to 5 years

• Safety and tolerability as measured by number and grade of toxicity events

  through study completion, an average of 1 year

Study Arms (1)

AZD6738 + Durvalumab Cohort

EXPERIMENTAL

This is a study enrolling advanced BTC patients who have been previously treated with immunotherapy, to explore the combination of AZD6738+durvalumab

Drug: AZD6738; Drug: Durvalumab

Interventions

AZD6738 DRUG

AZD6738 (240 ) mg bid on D15-D28 Every 4 weeks

AZD6738 + Durvalumab Cohort

Durvalumab DRUG

Durvalumab 1500 mg iv on D1 Every 4 weeks

AZD6738 + Durvalumab Cohort

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent and any locally-required authorization obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
• Age \> 20 years at time of study entry
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy of \> 16weeks
• Histologically proven BTC, including intrahepatic cholangiocarcinoma, extrahepatic bile duct cancer, gallbladder cancer, ampulla of vater cancer
• Unresectable or recurrent
• Failed immunotherapy for their advanced BTC (the patient may have also received chemotherapy in the 1 or 2L)
• At least one measurable lesion that can be accurately assessed at baseline by computed tomography (CT) (magnetic resonance imaging \[MRI\] where CT is contraindicated) and is suitable for repeated assessment as per RECIST 1.1.
• Body weight \>30kg
• Adequate normal organ and marrow function measured within 28 days prior to administration of study treatment as defined below :
• Haemoglobin ≥9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelet count ≥ 100x 109/L
• Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). (This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.)
• AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN

You may not qualify if:

• Participation in another clinical study with an investigational product during the last 3 weeks
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
• Any previous treatment with ATR inhibitor
• 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
• Receipt of the last dose of anti-cancer therapy (chemotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) within 21 days of the first dose of study drug .2 The minimum washout period for immunotherapy is 42 days
• Mean QT interval:
• Mean resting corrected QT interval (QTc) \>470 msec for females and \>450 for men, obtained from 3 electrocardiograms (ECGs) 2-5 minutes apart using the Fredericia formula
• \- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as congestive heart failure, unstable angina pectoris, acute myocardial infarction, hypokalaemia, congenital long QT syndrome, immediate family history of long QT syndrome or unexplained sudden death under 40 years of age, conduction abnormality not controlled with pacemaker or medication.
• Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. The following are exceptions to this criterion
• The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
• Systemic corticosteroids at physiologic doses not to exceed \<\<10 mg/day\>\> of prednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician.

Sponsors & Collaborators

• Seoul National University Hospital: lead

Study Sites (1)

Seoul National University Hospital

Seoul, 110-744, South Korea

RECRUITING

MeSH Terms

Conditions

Bile Duct Neoplasms

Interventions

ceralasertib; durvalumab

Condition Hierarchy (Ancestors)

Biliary Tract Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 25, 2020
• First Posted: March 6, 2020
• Study Start: June 25, 2020
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2025
• Last Updated: April 19, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)