Phase II Study of Immunotherapy With Durvalumab (MEDI4736) or Durvalumab and Tremelimumab, Both Combined With Y-90 SIRT Therapy in Advanced Stage Intrahepatic Biliary Tract Cancer (BTC)

Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest8 sites in 1 country50 target enrollmentNovember 1, 2019

ConditionsIntrahepatic Cholangiocarcinoma

InterventionsDurvalumab Tremelimumab

DrugsDurvalumab Tremelimumab

Overview

Phase: Phase 2
Intervention: Durvalumab
Conditions: Intrahepatic Cholangiocarcinoma
Sponsor: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Enrollment: 50
Locations: 8
Primary Endpoint: Objective Response rate (ORR) according to RECIST 1.1
Status: Active, not recruiting
Last Updated: 4 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

A multicenter Phase II, randomized, prospective, open-label Trial investigating the clinical impact on combining Specific Internal Radiotherapy (SIRT) with the PD1-L Inhibitor Durvalumab and the CTLA-4 Inhibitor Tremelimumab in patients with intrahepatic Biliary Tract Cancer

Detailed Description

IMMUWHY Phase II Clinical Trial will test the Addition of the immunotherapeutic agents Durvalumab and Tremelimumab after an initial Standard of Care SIRT in patients suffering from non-resectable intrahepatic Biliary Tract Cancer. Patients will be randomized into two experimental arms, one receiving Durvalumab only, the other one receiving Durvalumab + Tremelimumab. Clinical Outcomes will be compared vs. historical datasets.

Registry

clinicaltrials.gov

Start Date

November 1, 2019

End Date

December 1, 2027

Last Updated

4 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Fully-informed written consent and locally required authorization (European Union \[EU\]: General Data Privacy Regulation (GDPR)) obtained from the patient prior to performing any protocol-related procedures, including screening evaluations.
•Age ≥ 18 years.
•Histologically documented diagnosis of locally-advanced OR limited metasized intrahepatic BTC not amenable to curative treatment (tumor resection or ablation), specified as
•Tumor being confined to the liver or
•In case of presence of extrahepatic lesions, metastasis must be stable AND of limited extent\* AND patient must have a potential benefit from study participation in comparison to standard of care systemic therapy per local tumor board evaluation.
•\*Limited extent is defined in this protocol as presence of
•EITHER ≤3 malignant extrahepatic lymph nodes (short axis diameter ≥3cm)
•OR metastatic lesions in one organ other than liver (if only single lesion is present diameter MUST be \< 3cm; if up to 3 lesions in one organ each lesion MUST be ≤ 1cm).
•Presence of peritoneal or brain metastatsis excludes patients from study participation (see exclusion criterion #4)
•Tumor tissue (block or at least 4 slides) is available for translational research.

Exclusion Criteria

•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.
•Participation in another clinical study with an investigational product within 21 days prior to the first dose of the study treatment.
•Prior immunotherapy or use of other investigational agents, including prior treatment with an anti-Programmed Death receptor-1 (PD-1), anti-Programmed Death-1 ligand-1 (PD-L1), anti-PD-L2, or anti-cytotoxic T-lymphocyte associated antigen-4 (anti-CTLA-4) antibody, therapeutic cancer vaccines, apart from durvalumab and pembrolizumab as PD-L1 inhibitor in first line therapy.
•Presence of peritoneal carcinomatosis or brain metastases.
•Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
•Any concurrent chemotherapy, investigational product (IP), biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer related conditions (eg, hormone replacement therapy) is acceptable.
•Prior radiotherapy treatment before the first dose of any study drug.
•Major surgery (as defined by the Investigator) within 4 weeks prior to enrollment into the study; patients must have recovered from effects of any major surgery. Note: Local non-major surgery for palliative intent (e.g. surgery of isolated lesions, per-cutaneous biliary drainage or biliary stenting) is acceptable.
•Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g. colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], celiac disease, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis\].
•Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, , serious active, uncontrolled, gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.

Arms & Interventions

Arm 2

Durvalumab in combination with Tremelimumab

Intervention: Durvalumab

Arm 1

Durvalumab

Intervention: Durvalumab

Arm 2

Durvalumab in combination with Tremelimumab

Intervention: Tremelimumab

Outcomes

Primary Outcomes

Objective Response rate (ORR) according to RECIST 1.1

Time Frame: 20 months

Proportion of allocated subjects with best response of complete or partial response

Secondary Outcomes

Duration of response (DoR)(From first measurement of CR or PR per RECIST 1.1 until disease progression occurs (up to 43 months until Study Closure))
Progression free survival (PFS)(From date of randomization until disease progression occurs (up to 43 months until Study Closure))
Safety (rate of adverse events)(From first patient included until study closure (approx. 43 months after First Patient Included))
Overall Survival (OS)(Date of enrollment until date of death if applicable (up to 43 months until Study Closure))