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JOURNAL ONKOLOGIE – STUDIE

Immunotherapy Combined With Y-90 SIRT Therapy in Advanced Stage Intrahepatic Biliary Tract Cancer (BTC)

Rekrutierend

NCT-Nummer:
NCT04238637

Studienbeginn:
November 2019

Letztes Update:
21.02.2021

Wirkstoff:
Durvalumab, Tremelimumab

Indikation (Clinical Trials):
Cholangiocarcinoma, Biliary Tract Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

Collaborator:
AstraZeneca

Studienleiter

Salah-Eddin Al-Batran, Professor
Study Director
IKF Klinische Krebsforschung GmbH

Kontakt

Arndt Vogel, Professor
Kontakt:
Phone: +49 511 5326
Phone (ext.): 760
E-Mail: Vogel.Arndt@mh-hannover.de
» Kontaktdaten anzeigen
Doerthe Vortmeyer, Doctor
Kontakt:
Phone: +49 069 7601
Phone (ext.): 4196
E-Mail: vortmeyer.doerthe@ikf-khnw.de
» Kontaktdaten anzeigen

Studienlocations (1 von 1)

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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

- 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.

4. Patients with prior chemotherapy can be enrolled if ONE of the following criteria is

met:

- Capecitabin or gemcitabine+cisplatin in the adjuvant setting

- Experienced progressive disease under gemcitabine+cisplatin therapy in the

advanced setting

- Stable disease after 3 months of gemcitabine+cisplatin treatment

5. 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

- hepatic tumor load > 50%

- any Gastrointestinal deposition that cannot be corrected via angiographic

techniques

- irreversibly elevated serum bilirubin

- renal insufficiency

- increased pulmonary shunt fraction being able to deliver > 16.5 mCi to the lungs

- gastrointestinal ulceration

- hepatic dysfunction

- biliary complications

- portal hypertension

- vascular injury and lymphopenia.

6. Performance status (PS) ≤ 1 (ECOG scale).

7. Body weight >30 kg

8. At least one measurable site of disease as defined by RECIST 1.1 criteria.

9. Adequate bone marrow and renal function

10. Adequate hepatic function (with stenting for any obstruction, if required)

11. Female patients with reproductive potential must have a negative urine or serum

pregnancy test within 7 days prior to start of trial.

12. 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.

13. The patient is willing and able to comply with the protocol for the duration of the

study, including hospital visits for treatment and scheduled follow-up visits and

examinations.

14. Must have a life expectancy of at least 12 weeks.

15. If patient has concurrent Hepatitis B virus (HBV) or Hepatitis C virus (HCV)

infection, meets the following criteria:

- Patients with HBV or HCV infection should be monitored for viral levels during

study participation.

- Patients with detectable hepatitis B surface antigen (HBsAg) or detectable HBV

DNA should have HBV DNA < 100 IU/ml and should be managed per local treatment

guidelines.

Controlled (treated) hepatitis B subjects will be allowed if they started treatment at the

time point of enrollment into the study by the latest and treatment is continued during

study participation and for ≥ 6 months after end of study treatment.

- HCV patients with advanced BTC are mostly not treated for their HCV infection. However,

patients treated for HCV are considered suitable for inclusion if antiviral therapy has

been completed ≥ 30 days prior to first administration of study drug.

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

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].

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:

- Malignancy 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

- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence

of disease

- Adequately treated carcinoma in situ without evidence of disease

13. History of leptomeningeal carcinomatosis

14. Brain metastases or spinal cord compression. Patients with suspected brain metastases

at screening should have a CT/ MRI of the brain prior to study entry.

15. History of active primary immunodeficiency

16. History of allogenic organ transplantation.

17. Active infection including tuberculosis (clinical evaluation that includes clinical

history, physical examination and radiographic findings, and TB testing in line with

local practice), or human immunodeficiency virus (positive HIV 1/2 antibodies) or

active hepatitis B/hepatitis C co-infection.

18. Current or prior use of immunosuppressive medication within 14 days before the first

dose of durvalumab or tremelimumab.

19. Female patients who are pregnant or breastfeeding or male or female patients of

reproductive potential who are not willing to employ highly effective birth control

from screening to 180 days after the last dose of durvalumab.

20. Known allergy or hypersensitivity to any of the IMPs or any of the constituents of the

product.

21. Any co-existing medical condition that in the investigator's judgement will

substantially increase the risk associated with the patient's participation in the

study.

22. Patient who has been incarcerated or involuntarily institutionalized by court order or

by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG.

23. Patients who are unable to consent because they do not understand the nature,

significance and implications of the clinical trial and therefore cannot form a

rational intention in the light of the facts [§ 40 Abs. 1 S. 3 Nr. 3a AMG].

24. Receipt of live attenuated vaccine within 30 days prior to the first administration of

any of the IMPs and without need to receive any live attenuated vaccines during study

conduct and for up to 30 days after end of Durvalumab treatment or 90 days after end

of Tremelimumab treatment respectively.

Studien-Rationale

Primary outcome:

1. 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 outcome:

1. Safety (rate of adverse events) (Time Frame - From first patient included until study closure (approx. 43 months after First Patient Included)):
Type, incidence and severity of AEs and SAEs graded according to NCI CTCAE v5.0

2. Duration of response (DoR) (Time Frame - From first measurement of CR or PR per RECIST 1.1 until disease progression occurs (up to 43 months until Study Closure)):
Time from that the measurement criteria are first met for CR or PR (whichever is first recorded) until the first date that the PD is objectively documented or death

3. Progression free survival (PFS) (Time Frame - From date of randomization until disease progression occurs (up to 43 months until Study Closure)):
Time from the date of randomization to the date of first observed disease progression (investigator assessment according to RECIST 1.1) or death from any cause

4. Overall Survival (OS) (Time Frame - Date of enrollment until date of death if applicable (up to 43 months until Study Closure)):
time from the date of treatment allocation to the date of death.

Studien-Arme

  • Experimental: Arm 1
    Durvalumab
  • Experimental: Arm 2
    Durvalumab in combination with Tremelimumab

Geprüfte Regime

  • Durvalumab (Other Name: MEDI4736):
    Durvalumab IV (intravenous Infusion)
  • Tremelimumab (Study treatment):
    Tremelimumab IV (intravenous Infusion)

Quelle: ClinicalTrials.gov


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