A phase II study of immunotherapy with durvalumab (MEDI4736) or durvalumab and tremelimumab, both combined with Y-90 SIRT therapy in patients with advanced stage intrahepatic biliary tract cancer (BTC) scheduled to receive Y-90 SIRT therapy as standard of care

Phase 1

• Conditions: Intrahepatic Biliary Tract Carcinoma; MedDRA version: 20.0Level: LLTClassification code 10008594Term: Cholangiocarcinoma non-resectableSystem Organ Class: 100000004864; MedDRA version: 20.0Level: LLTClassification code 10073077Term: Intrahepatic cholangiocarcinomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-004778-81-DE
• Lead Sponsor: Institut für Klinische Krebsforschung IKF GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-07-09
• Last Update Posted: 26 February 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1.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.
2.Age = 18 years.
3.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
oEITHER =3 malignant extrahepatic lymph nodes (short axis diameter =3cm)
oOR 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).
oPresence of peritoneal or brain metastatsis excludes patients from study participation
4.Has been considered candidate for standard-of-care Y-90 SIRT therapy per Investigator decision and after prior consultation with the tumor board if available at site and does not display contraindications against SIRT.
Contraindications against SIRT would be
ohepatic tumor load > 50%
oAny Gastrointestinal deposition that cannot be corrected via angiographic techniques
oirreversibly elevated serum bilirubin
orenal insufficiency
oincreased pulmonary shunt fraction being able to deliver > 16.5 mCi to the lungs
ogastrointestinal ulceration
ohepatic dysfunction
obiliary complications
oportal hypertension
ovascular injury and lymphopenia.
5.Performance status (PS) = 1 (ECOG scale).
6.Body weight >30 kg
7.At least one measurable site of disease as defined by RECIST 1.1 criteria.
8.Adequate bone marrow and renal function including the following:
oHemoglobin = 9.0 g/dL;
oabsolute neutrophil count = 1.5 x 103/L;
oplatelets =100x 109 /L;
oCreatinine = 1.5 x upper normal limit.
oCalculated creatinine clearance =40 mL/min as determined by the Cockcroft-Gault equation
9.Adequate hepatic function (with stenting for any obstruction, if required) including the following:
o Serum bilirubin = 1.5 x institutional upper limit of normal (ULN);
o AST (SGOT) / ALT (SGPT) = 2.5x institutional ULN
(NOTE: if liver metastases are present AST / ALT must be = 5x institutional ULN;
oprothrombin time ? 60%;
oalbumin ? 30 g/L.
10.Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial.
11.Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
oWomen <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
oWomen =50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more

Exclusion Criteria

1.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.
2.Participation in another clinical study with an investigational product within 21 days prior to the first dose of the study treatment.
3.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.
4. Presence of peritoneal carcinomatosis or brain metastases.
5.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
oPatients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab and tremelimumab may be included only after consultation with the Coordinating Investigator.
6.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.
7.Prior radiotherapy treatment before the first dose of any study drug.
8.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.
9.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]. The following are exceptions to this criterion:
oPatients with vitiligo or alopecia
oPatients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
oAny chronic skin condition that does not require systemic therapy
oPatients without active disease in the last 5 years may be included but only after consultation with the study physician
10.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.
11.History of non-infectious pneumonitis requiring steroids, or patients with Grade = 2 pneumonitis.

12.History of another primary malignancy except for:
oMalignancy treated with curative intent and with no known active disease = 5 years before the first dose of IP and of low potential risk for recurrence
oAdequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
oAdequately treated carcinoma in situ without evidence of disease
13.History of leptomeningeal carcinomatosis
14.Brain metastases or spinal cor

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified