DDR-Umbrella Study of DDR Targeting Agents in Advanced Biliary Tract Cancer

NCT04298021 | Active Not Recruiting Phase 2

• 1 other identifier: BTC-DDR Umbrella
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

To assess the effect of AZD6738 and Durvalumab combination or AZD6738 and Olaparib combination in biliary tract cancer patients who have failed to 1st-line chemotherapy.

Conditions

Bile Duct Cancer; Chemotherapy Effect

Outcome Measures

Primary Outcomes (2)

• Disease control rate of AZD6738 + Durvalumab cohort

  Disease control rate based on RECIST v1.1.

  through study completion, an average of 1 year

• Disease control rate of AZD6738 + Olaparib cohort

  Disease control rate based on RECIST v1.1.

  through study completion, an average of 1 year

Secondary Outcomes (12)

• Overall response rate of AZD6738 + Durvalumab cohort

  through study completion, an average of 1 year

• progression-free survival of AZD6738 + Durvalumab cohort

  through study completion, an average of 1 year

• duration of response of AZD6738 + Durvalumab cohort

  through study completion, an average of 1 year

• overall survival of response of AZD6738 + Durvalumab cohort

  every 12 weeks until death or up to 5 years

• Safety and tolerability of AZD6738 + Durvalumab cohort measured by number and grade of toxicity events

  through study completion, an average of 1 year

Study Arms (2)

AZD6738 + Durvalumab

EXPERIMENTAL

* Durvalumab 1500 mg iv on D1 * AZD6738 240 mg bid on D15-D28 Every 4 weeks C1D1 dose of durvalumab will be delivered, and AZD6738 of 240 mg bid will be dosed at D15-D28. Every cycle consists of 4 weeks.

Drug: AZD6738; Drug: Durvalumab

AZD6738 + Olaparib

EXPERIMENTAL

* AZD6738 160 mg qd on D1-D7 * Olaparib 300 mg bid on D1-D28 Every 4 weeks Every cycle consists of 4 weeks. AZD6738 of 160 mg qd will be administered on D1-D7. Olaparib will be delivered as 300 mg bid dose on D1-D28.

Drug: AZD6738; Drug: Olaparib

Interventions

AZD6738 DRUG

* In AZD6738+Durvalumab cohort \- AZD6738 240 mg bid on D15-D28 Every 4 weeks * In AZD6738+ Olaparib cohort - AZD6738 160 mg qd on D1-7 Every 4 weeks

AZD6738 + Durvalumab; AZD6738 + Olaparib

Durvalumab DRUG

Durvalumab 1500 mg iv on D1 Every 4 weeks

AZD6738 + Durvalumab

Olaparib DRUG

Olaparib 300 mg bid on D1-28 Every 4 weeks

AZD6738 + Olaparib

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 to 1st-line chemotherapy for their advanced BTC (IO is not allowed)
• 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 (for durvalumab cohort)
• Adequate normal organ and marrow function measured within 28 days prior to administration of study treatment as defined below :
• Haemoglobin ≥9.0 g/dL (\>10 for olaparib cohort with no transfusion within the previous 28 days)
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 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 Immune check point inhibitor, ATR or PARP inhibitor, including Olaparib.
• Whole blood transfusions in the last 120 days prior to entry to the study in olaparib cohort (packed red blood cells and platelet transfusions are acceptable outside of 28 days prior to treatment
• 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, immunotherapy, 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.
• In AZD6738+Durvalumab cohort, current or prior use of immunosuppressive medication within 14days (use 28 days if combining durvalumab with a novel agent) 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)
• Also, Any of the following cardiac diseases currently or within the last 6 months (by New York Heart Association (NYHA) ≥ Class 2 where applicable):

Sponsors & Collaborators

• Seoul National University Hospital: lead

Study Sites (1)

Seoul National University Hospital

Seoul, 110-744, South Korea

Location

MeSH Terms

Conditions

Bile Duct Neoplasms

Interventions

ceralasertib; durvalumab; olaparib

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• 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, 2024
• Last Updated: April 19, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)