CholangiocarcinomaPhase 2NCT02374489
A Phase II Trial of LDK378 in ROS1 and /or ALK Over-expressed Advanced Intrahepatic or Hilar Cholangiocarcinoma
A Phase 2 study testing LDK378 in people with Cholangiocarcinoma, run by National Health Research Institutes, Taiwan at 2 sites in Taiwan.
Trial 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 … Read more about this study
- Who is it for?
- Ages 20 to 75 years
- Conditions the study is for
- Cholangiocarcinoma
- What is being tested?
- LDK378
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 2 sitesTaiwan
- Study dates
- Mar 2015to Jan 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1.Histological or cytologically confirmed diagnosis of intrahepatic or hilar cholangiocarcinoma that demonstrates ALK and/or ROS1 over-expression by IHC (3+).
- 2.Locally advanced with inoperable or metastatic disease status
- 3.ECOG performance status 0-2.
- 4.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.
- 6.The following laboratory criteria have been met:
- •Absolute neutrophil count (ANC) ≥1.5 x 109/L
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- 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.
Who cannot join
- 1.Patients with known hypersensitivity to any of the excipients of LDK378 (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate).
- 2.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.
- 3.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.
- 5.Presence or history of a malignant disease other than cholangiocarcinoma that has been diagnosed and/or required therapy within the past year and is not undergoing active anticancer treatment. Exceptions to this exclusion include the following: completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type.
- 6.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).
- 7.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.
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- 8.Impaired GI function or GI disease that may alter absorption of LDK378 or inability to swallow up to five LDK378 capsules daily.
- 9.Ongoing GI adverse events > grade 2 (e.g. nausea, vomiting, or diarrhea) at the start of the study.
- 10.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.
- 12.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.
- In case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment.
- 13.Sexually active males unless they use a condom during intercourse while taking drug and for 3 months after the last dose of study treatment. Male patients for 3 months should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.
Trial locations and contacts
2 sites in 1 country.
Taiwan2 sites
National Taiwan University Hospital
Taipei, 112
National Cheng Kung University Hospital
Taipei, 704
About this study
Official title: A Phase II Trial of LDK378 as the First or Second-line Therapy in ROS1 and /or ALK Over-expressed Advanced Intrahepatic or Hilar Cholangiocarcinoma
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
Read the detailed description
Sample size: LDK378 will be considered as an active agent and deserved for further development. Considering 10% dropout rate, total 34 patients will be included.
Step 1: 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.
Step 2: Evaluation of tumor response according to RECIST 1.1 version
- Evaluation will be done at baseline and every 6 weeks
- Evaluation will be performed with CT or MRI and the response is defined as follows:
- Complete response - the disappearance of all target lesions.
- Partial response - at least a 30% decrease in the sum of the longest diameter of target lesions compared to the baseline sum longest diameter.
- Progressive disease - at least a 20% increase in the sum of the longest diameter of target lesions compared to the smallest sum longest diameter recorded since the treatment started or the appearance of one, or more new lesions, or reappearance of any lesion that had disappeared, or clear worsening of any assessable disease, or appearance of any new lesion or site.
- Stable disease - neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, compared to the smallest sum longest diameter since the treatment started
- Conditions
- Cholangiocarcinoma
- Being tested
- LDK378
- Medical subject headings
- Cholangiocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LDK378Drug
Also called ceritinib(Zykadia)
LDK378 750 mg ( p.o.) daily, with 3 week as a treatment cycle.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: LDK378 |
What is being measured
The primary outcome is the main question the study is designed to answer.
objective response rate
Evaluation of tumor response according to RECIST 1.1 version
Measured: three year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2015 (estimated)
- Study startMar 2015
- Primary completionJan 2018
- Study completionJan 2018
Why it stopped: ROS1 in IHC and gene rearrangement result can not match。No tumor response。
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CholangiocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Health Research Institutes, Taiwan
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02374489
- Sponsor's protocol ID
- T3214
- Status last verified
- Jan 2018
- First submitted
- 23 Feb 2015
- Last updated
- 5 Apr 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of LDK378 as the First or Second-line Therapy in ROS1 and /or ALK Over-expressed Advanced Intrahepatic or Hilar Cholangiocarcinoma
- ClinicalTrials.gov ID
- NCT02374489
- Acronym / sponsor ID
- T3214
- Conditions
- Cholangiocarcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: ROS1 in IHC and gene rearrangement result can not match。No tumor response。
- Enrolment
- 9 participants (actual)
- Lead sponsor
- National Health Research Institutes, TaiwanUniversity, hospital or other
- Collaborators
- National Cheng-Kung University Hospital, National Taiwan University Hospital
- Study start
- Mar 2015
- Primary completion
- Jan 2018 (actual)
- Study completion
- Jan 2018 (actual)
- First posted
- 27 Feb 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
Sample size: LDK378 will be considered as an active agent and deserved for further development. Considering 10% dropout rate, total 34 patients will be included.
Step 1: 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.
Step 2: Evaluation of tumor response according to RECIST 1.1 version
- Evaluation will be done at baseline and every 6 weeks
- Evaluation will be performed with CT or MRI and the response is defined as follows:
- Complete response - the disappearance of all target lesions.
- Partial response - at least a 30% decrease in the sum of the longest diameter of target lesions compared to the baseline sum longest diameter.
- Progressive disease - at least a 20% increase in the sum of the longest diameter of target lesions compared to the smallest sum longest diameter recorded since the treatment started or the appearance of one, or more new lesions, or reappearance of any lesion that had disappeared, or clear worsening of any assessable disease, or appearance of any new lesion or site.
- Stable disease - neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, compared to the smallest sum longest diameter since the treatment started
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| single-arm studies | Experimental | Drug: LDK378LDK378 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 |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 1.Histological or cytologically confirmed diagnosis of intrahepatic or hilar cholangiocarcinoma that demonstrates ALK and/or ROS1 over-expression by IHC (3+).
- 2.Locally advanced with inoperable or metastatic disease status
- 3.ECOG performance status 0-2.
- 4.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.
- •Absolute neutrophil count (ANC) ≥1.5 x 109/L
Key exclusion criteria (18 listed)
- 1.Patients with known hypersensitivity to any of the excipients of LDK378 (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate).
- 2.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.
- 3.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.
- 5.Presence or history of a malignant disease other than cholangiocarcinoma that has been diagnosed and/or required therapy within the past year and is not undergoing active anticancer treatment. Exceptions to this exclusion include the following: completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type.
- 6.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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LDK378Also: ceritinib(Zykadia)LDK378 750 mg ( p.o.) daily, with 3 week as a treatment cycle. | Drug | single-arm studies |
Primary outcome
objective response rate
Time frame: three year
Evaluation of tumor response according to RECIST 1.1 version
Results and safety
The study was stopped early (reason given: ROS1 in IHC and gene rearrangement result can not match。No tumor response。). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LDK378 in people with Cholangiocarcinoma, run by National Health Research Institutes, Taiwan at 2 sites in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: ROS1 in IHC and gene rearrangement result can not match。No tumor response。). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
objective response rate (time frame: three year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2018.