A Phase II Trial of LDK378 in ROS1 and /or ALK Over-expressed Advanced Intrahepatic or Hilar Cholangiocarcinoma

NCT02374489 | Terminated Phase 2 DMC

• 1 other identifier: T3214
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief Summary

Primary objective: To investigate the objective response rate in patients with ROS1 or ALK over-expressed locally advanced, or metastatic intrahepatic or hilar cholangiocarcinoma receiving LDK378 Secondary objectives:The progression-free survival ,The disease control rate ,The overall survival ,The toxicity profiles , The correlation between clinical outcomes and the potential predictive biomarker for tumor response

Conditions

Cholangiocarcinoma

Outcome Measures

Primary Outcomes (1)

• objective response rate

  Evaluation of tumor response according to RECIST 1.1 version

  three year

Study Arms (1)

single-arm studies

EXPERIMENTAL

LDK378 in suitable patients: Collect tumor tissue for immunohistochemistry staining to confirm the status of ROS1 or ALK expression. If the patient fits all criteria, LDK378 750 mg ( p.o.) daily, with 3 week as a treatment cycle

Drug: LDK378

Interventions

LDK378 DRUG

LDK378 750 mg ( p.o.) daily, with 3 week as a treatment cycle.

Also known as: ceritinib(Zykadia)

single-arm studies

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological or cytologically confirmed diagnosis of intrahepatic or hilar cholangiocarcinoma that demonstrates ALK and/or ROS1 over-expression by IHC (3+).
• Locally advanced with inoperable or metastatic disease status
• ECOG performance status 0-2.
• Aged no less than 20 years and no more than 75 years, at the time of acquisition of informed consent 5.Patients must have recovered from all toxicities related to prior anticancer therapies to ≤ grade 2 (CTCAE v 4.03), provided that concomitant medication is given prior to initiation of treatment with LDK378. Exception to this criterion: patients with any grade of alopecia are allowed to enter the treatment.
• The following laboratory criteria have been met:
• Absolute neutrophil count (ANC) ≥1.5 x 109/L
• Hemoglobin (Hgb) ≥ 9 g/dL
• Platelets ≥ 75 x 109/L
• Serum total bilirubin ≤1.5 x upper limit of normal (ULN), except for patients with biliary tract obstruction statis post drainage or stent may be included if total bilirubin ≤3.0 x ULN and direct bilirubin≤ 1.5 x ULN
• Aspartate transaminase (AST) \< 3.0 x ULN, except for patients with liver metastasis, who are only included if AST \< 5 x ULN; alanine transaminase (ALT) \< 3.0 x ULN, except for patients with liver metastasis, who are only included if ALT \< 5 x ULN
• Calculated or measured creatinine clearance (CrCL) ≥ 30 mL/min 7.Patient must have the following laboratory values or have the following laboratory values corrected with supplements to be within normal limits at screening:
• Potassium ≥ 1.0 x lower limit of normal (LLN)
• Magnesium ≥ 1.0 x LLN
• Phosphorus ≥ 1.0 x LLN
• Total calcium (corrected for serum albumin) ≥ 1.0 x LLN 8.At least one, not previously irradiated, measurable lesion according to RECIST (version 1.1) 9.Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other procedures.

You may not qualify if:

• Patients with known hypersensitivity to any of the excipients of LDK378 (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate).
• Patients with symptomatic CNS metastases who are neurologically unstable or have required increasing doses of steroids within the 1 week prior to study entry to manage CNS symptoms.
• Prior therapy with LDK378. 4.Other anti-tumor agent such as systemic chemotherapy, immunotherapy or targeted therapy within 2 weeks before the commencement of study treatment.
• Patients with known history of extensive disseminated bilateral interstitial fibrosis or interstitial lung disease, including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, obliterative bronchiolitis, and clinically significant radiation pneumonitis (i.e. affecting activities of daily living or requiring therapeutic intervention).
• Patient has clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months), such as:unstable angina within 6 months prior to screening;myocardial infarction within 6 months prior to screening;history of documented congestive heart failure (New York Heart Association functional classification III-IV);uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) ≥ 160 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 100 mm Hg, with or without antihypertensive medication ;initiation or adjustment of antihypertensive medication(s) is allowed prior to screening;ventricular arrhythmias; supraventricular and nodal arrhythmias not controlled with medication;other cardiac arrhythmia not controlled with medication;corrected QTc (male: QTc \>450 msec; female: QTc\> 470 msec ) using Bazett correction on the screening ECG.
• Impaired GI function or GI disease that may alter absorption of LDK378 or inability to swallow up to five LDK378 capsules daily.
• Ongoing GI adverse events \> grade 2 (e.g. nausea, vomiting, or diarrhea) at the start of the study.
• Receiving medications that meet one of the following criteria and that cannot be discontinued at least 1 week prior to the start of treatment with LDK378 and for the duration of participation:Medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes .Strong inhibitors or strong inducers of CYP3A4/5 ;Medications with a low therapeutic index that are primarily metabolized by CYP3A4/5, CYP2C8 and/or CYP2C9 ;Therapeutic doses of warfarin sodium (Coumadin) or any other coumadin-derived anti-coagulant. Anticoagulants not derived from warfarin are allowed (eg, dabigatran, rivaroxaban, apixaban).;increasing doses of corticosteroids;enzyme-inducing anticonvulsive agents;herbal supplements 11.Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 3 months after the last dose of study treatment. Highly effective contraception methods include:Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
• Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
• Male sterilization (at least 6 months prior to screening) with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate. For female subjects on the study the vasectomized male partner should be the sole partner for that subject.
• Combination of any two of the following (a+b or a+c or b+c):
• Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate \< 1%), for example hormone vaginal ring or transdermal hormone contraception.
• Placement of an intrauterine device (IUD) or intrauterine system (IUS).
• Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.

Sponsors & Collaborators

• National Health Research Institutes, Taiwan: lead
• National Cheng-Kung University Hospital: collaborator
• National Taiwan University Hospital: collaborator

Study Sites (2)

National Taiwan University Hospital

Taipei, 112, Taiwan

Location

National Cheng Kung University Hospital

Taipei, 704, Taiwan

Location

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

ceritinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2015
• First Posted: February 27, 2015
• Study Start: March 1, 2015
• Primary Completion: January 1, 2018
• Study Completion: January 1, 2018
• Last Updated: April 5, 2018

Record last verified: 2018-01

Locations

TW (2)