Nal-IRI and 5-FU Compared to 5-FU in Patients With Cholangio- and Gall

Nal-IRI and 5-FU Compared to 5-FU in Patients With Cholangio- and Gallbladder Carcinoma Previously Treated With Gemcitabine-based Therapies (NALIRICC)

Not open yet.

https://clinicaltrials.gov/ct2/show/NCT03043547

Purpose
is an open label, randomized, multicenter phase II trial

Condition Intervention Phase
Cholangiocarcinoma Non-resectable
Cholangiocarcinoma Metastatic
Cholangiocarcinoma of the Gallbladder
Cholangiocarcinoma Advanced
Drug: nal-IRI
Drug: 5-FU
Drug: leucovorin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of Nal-IRI and 5-Fluorouracil Compared to 5-Fluorouracil in Patients With Cholangio- and Gallbladder Carcinoma Previously Treated With Gemcitabine-based Therapies

Resource links provided by NLM:

Genetics Home Reference related topics: cholangiocarcinoma
Drug Information available for: Fluorouracil Gemcitabine
Genetic and Rare Diseases Information Center resources: Gallbladder Cancer
U.S. FDA Resources

Further study details as provided by AIO-Studien-gGmbH:

Primary Outcome Measures:
progression-free survival [ Time Frame: approx 42 months ]

Secondary Outcome Measures:
Overall survival [ Time Frame: approx 42 months ]
Objective tumor response rate (ORR) according to RECIST 1.1 [ Time Frame: approx 42 months ]
Response Evaluation Criteria in Solid Tumors (RECIST 1.1.)

Toxicity/Safety [ Time Frame: approx 42 months ]
according to Common Terminology Criteria for Adverse Events

Health related Quality of Life [ Time Frame: approx 42 months ]
EORTC QLQ-C30

Other Outcome Measures:
biomarkers [ Time Frame: approx 42 months ]
Ca-19-9, CEA, CRP serum levels

Immunohistochemistry of Carboxylesterase (CES) [ Time Frame: approx 42 months ]
Analyse whole blood [ Time Frame: approx 42 months ]
will be collected to potentially identify factors that may correlate with tumour response, sensitivity or resistance to nal-IRI

Analyse plasma [ Time Frame: approx 42 months ]
will be collected to potentially identify factors that may correlate with tumour response, sensitivity or resistance to nal-IRI

Estimated Enrollment: 100
Anticipated Study Start Date: May 2017
Estimated Study Completion Date: April 2021
Estimated Primary Completion Date: November 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nal-IRI + 5-FU + leucovorin (Arm A)
nal-IRI [Irinotecan liposome] (80 mg/m2 as a 1.5 hour infusion), 5-FU [5-Fluorouracil] (2400 mg/m2 as 46 hour infusion) and leucovorin (400 mg/m2 as 0.5 hour infusion) (q2w)
Drug: nal-IRI
nal-IRI [Irinotecan liposome] (80 mg/m2 as a 1.5 hour infusion)
Drug: 5-FU
5-FU [5-Fluorouracil] (2400 mg/m2 as 46 hour infusion)
Drug: leucovorin
leucovorin (400 mg/m2 as 0.5 hour infusion)
5-FU + leucovorin (Arm
Control intervention/standard arm: 5-FU (2400 mg/m2 as 46 hour infusion) and leucovorin (400 mg/m2 as 0.5 hour infusion) (q2w)
Drug: 5-FU
5-FU [5-Fluorouracil] (2400 mg/m2 as 46 hour infusion)
Drug: leucovorin
leucovorin (400 mg/m2 as 0.5 hour infusion)

Detailed Description:
The primary objective is to assess the efficacy of nal-IRI in gemcitabine pre-treated patients with advanced, unresectable and metastatic cholangio- and gallbladder carcinoma eligible for treatments after failure to respond to a gemcitabine-based treatment
Eligibility

Ages Eligible for Study: 18 Years and older (Adult, Senior)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
Criteria
Inclusion Criteria:

Written informed consent incl. participation in translational research and any locally-required authorization (EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
Age ≥ 18 years at time of study entry
Histologically or cytologically confirmed, non-resectable, locally advanced or metastatic cholangiocarcinoma or gall bladder carcinoma
Measurable or assessable disease according to RECIST 1.1
Documented disease progression after prior gemcitabine or gemcitabine containing therapy, in locally advanced or metastatic setting. Examples of permitted therapies include, but are not limited to:
Single agent gemcitabine
Any one gemcitabine-based regimen, with or without maintenance gemcitabine
ECOG performance status 0-1
Adequate blood count, liver-enzymes, and renal function:
ANC > 1,500 cells/μL without the use of hematopoietic growth factors; and
Platelet count ≥ 100 x 10^9/L (>100,000 per mm³) and
Hemoglobin > 9 g/dL (blood transfusions are permitted for patients with hemoglobin levels below 9 g/dL)
Serum total bilirubin ≤ 3x upper normal limit (ULN) (biliary drainage is allowed for biliary obstruction; elevated bilirubin should be caused by obstruction not impaired liver function as assessed by albumin and INR values):
Albumin levels ≥ 3.0 g/dL
Patients not receiving therapeutic anticoagulation must have an INR < 1.5 ULN and PTT < 1.5 ULN within 7 days prior to randomization. The use of full dose anticoagulants is allowed as long as the INR or PTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose for anticoagulants for at least three weeks at the time of randomization
AST (SGOT)/ALT (SGPT) ≤ 5 x institutional upper limit of normal
Serum Creatinine ≤ 1.5 x ULN and a calculated glomerular filtration rate ≥ 30 mL per minute
Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of treatment.
Subject is willing and able to comply with the protocol (including contraceptive measures) for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
Exclusion Criteria:

Active CNS metastases (indicated by clinical symptoms, cerebral oedema, steroid requirement, or progressive disease); patient should have been off steroids for at least 28 days prior to starting study therapy
Clinically significant gastrointestinal disorder including bleeding, inflammation, occlusion, or diarrhoea > grade 1
History of any second malignancy in the last 5 years; subjects with prior history of in-situ cancer or basal or squamous cell skin cancer are eligible. Subjects with other malignancies are eligible if they have been continuously disease free for at least 5 years.
Active uncontrolled infection, chronic infectious diseases, immune deficiency syndromes or an unexplained fever > 38.5°C during screening visits or on the first scheduled day of dosing (at the discretion of the investigator, patients with tumour fever may be enrolled), which in the investigator’s opinion might compromise the patient’s participation in the trial or affect the study outcome.
Premalignant hematologic disorders, e.g. myelodysplastic syndrome
Pre-existing lung disease
Clinically significant cardiovascular disease in (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) 6 months before enrollment
History of hypersensitivity to any of the study drugs or any excipient (nal-IRI, other liposomal products, fluoropyrimidines or leucovorin)
Allogeneic transplantation requiring immunosuppressive therapy or other major immunosuppressive therapy
Severe non-healing wounds, ulcers or bone fractions
Evidence of bleeding diathesis or coagulopathy
Major surgical procedures, except open biopsy, nor significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgical procedure during the course of the study except for surgery of central intravenous line placement for chemotherapy administration.
Medication that is known to interfere with any of the agents applied in the trial.
Female subjects who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control (failure rate of less than 1% per year). [Acceptable methods of contraception are:implants, injectable contraceptives, combined oral contraceptives, intrauterine pessaries (only hormonal devices), sexual abstinence or vasectomy of the partner].
Known Gilbert-Meulengracht syndrome
Any condition or comorbidity that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
Participation in another clinical study with an investigational product during the last 30 days before inclusion or 5 half-lifes of previously used trial medication, whichever is of longer duration.
Previous enrollment or randomization in the present study (does not include screening failure).
Previous enrollment in the NIFE trial [AIO-YMO/HEP-0315]
Involvement in the planning and/or conduct of the study (applies to both Baxalta staff and/or staff of sponsor and study site)
Patient who might be dependent on the sponsor, site or the investigator
Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG.
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].
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03043547

Contacts
Contact: Helge Schroeder Helge.Schroeder@aio-studien-ggmbh.de
Contact: Martha Kirstein, Dr. kirstein.martha@mh-hannover.de

Locations
Germany
Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover Not yet recruiting
Hannover, Germany, 30625
Contact: Arndt Vogel, Prof. vogel.arndt@mh-hannover.de
Sponsors and Collaborators
AIO-Studien-gGmbH
Baxalta GmbH
Shire
Investigators
Principal Investigator: Arndt Vogel, Prof. Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
More Information

Additional Information:
AIO – Working Group for Medical Oncology from the German Cancer Society This link exits the ClinicalTrials.gov site
AIO-Studien-gGmbH This link exits the ClinicalTrials.gov site

Responsible Party: AIO-Studien-gGmbH
ClinicalTrials.gov Identifier: NCT03043547 History of Changes
Other Study ID Numbers: AIO-HEP-0116 2016-003709-33 O16-33033
Study First Received: January 26, 2017
Last Updated: February 3, 2017
Individual Participant Data
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AIO-Studien-gGmbH:
nal-IRI
5-Fluorouracil

Additional relevant MeSH terms:
Cholangiocarcinoma
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gemcitabine
Fluorouracil
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 07, 2017