Tumors With Aberrations in ALKPhase 2NCT02465528
Ceritinib Rare Indications Study in ALK+ Tumors
A Phase 2 study testing Ceritinib (LDK378) in people with Tumors With Aberrations in ALK and Anaplastic Large Cell Lymphoma, run by Novartis Pharmaceuticals at 14 sites in 8 countries.
Trial summary
This is Proof-of-Concept (POC) study to assess the preliminary antitumor activity and safety and tolerablity using ceritinib (LDK378) in the treatment of life threatening tumors that are characterized by ALK genetic alteration (and/or overexpression in some diseases). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tumors With Aberrations in ALK, Anaplastic Large Cell Lymphoma, Inflammatory Myofibroblastic Tumor
- What is being tested?
- Ceritinib (LDK378)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 14 sitesin 8 countries
- Study dates
- 6 May 2016to 20 Aug 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient has a histologically or cytologically confirmed diagnosis of ALK positive (ALK+) tumor other than Non-Small Cell Lung Cancer (NSCLC).
- Patient must provide an archival or fresh tumor tissue before the first dose of the study drug for ALK testing at a Novartis designated central laboratory.
- Patient has WHO Performance Status (PS) ≤ 2
- Patient must have received at least one line of prior systemic treatment for recurrent, locally advanced and/or metastatic disease, and may have discontinued for:
- Disease progression as defined by RECIST 1.1 for solid tumors; by RANO for GBM and by Cheson assessment criteria for lymphoma, or
- Intolerance described as any discontinuation due to an AE of any grade despite appropriate supportive treatment
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- Patient has at least one measurable lesion as defined by appropriate guidelines. A lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation.
- Patient has received no chemotherapy, immunotherapy or stem cell therapy at least 4 weeks before starting ceritinib
- Radiotherapy and prior ALK inhibitors must be stopped at least 1 week prior to starting ceritinib
- Recovered from all toxicities related to prior anticancer therapies to grade ≤ 1 (Common Terminology Criteria for Adverse Events [CTCAE] v4.03).
Who cannot join
- Patient has ALK+lung cancer
- Patient with symptomatic CNS metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms.
- Patient with acute or chronic GI disease that may significantly alter the absorption of ceritinib.
- Patient with a history of pancreatitis or history of increased amylase or lipase that was due to pancreatic disease.
- Patient has history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis.
- Patient has clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months).
- Patient has evidence of active viral hepatitis, including Hepatitis A, B or C (testing for viral hepatitis is not mandatory).
- Patient has known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory).
Trial locations and contacts
14 sites in 8 countries.
14 sites in 8 countries
France3 sites
Novartis Investigative Site
Lyon, 69373
Novartis Investigative Site
Saint-Herblain Cédex, 44805
Novartis Investigative Site
Strasbourg, F 67085
South Korea3 sites
Novartis Investigative Site
Seoul, 03080
Novartis Investigative Site
Seoul, 03722
Novartis Investigative Site
Seoul, 06351
Spain2 sites
Novartis Investigative Site
Madrid, 28034
Novartis Investigative Site
Madrid, 28040
Thailand2 sites
Novartis Investigative Site
Bangkok, 10330
Novartis Investigative Site
Bangkok, 10700
About this study
Official title: A Phase II, Open Label, Multi-center, Multi-arm Study of Ceritinib in Patients With Advanced Solid Tumors and Hematological Malignancies Characterized by Genetic Abnormalities of Anaplastic Lymphoma Kinase (ALK)
This is Proof-of-Concept (POC) study to assess the preliminary antitumor activity and safety and tolerablity using ceritinib (LDK378) in the treatment of life threatening tumors that are characterized by ALK genetic alteration (and/or overexpression in some diseases).
- Conditions
- Tumors With Aberrations in ALK, Anaplastic Large Cell Lymphoma, Inflammatory Myofibroblastic Tumor, Glioblastoma
- Being tested
- Ceritinib (LDK378)
- Keywords
- ALK, GBM, hematological malignancy, anaplastic lymphoma kinase, glioblastoma, anaplastic large cell lymphoma, IMT, inflammatory myofibroblastic tumor
- Medical subject headings
- Lymphoma, Large-Cell, Anaplastic, Granuloma, Plasma Cell, Glioblastoma, Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ceritinib (LDK378)Drug
Ceritinib was to be administered orally once daily at a dose of 750 mg (5 capsules of 150 mg) on a continuous dosing schedule. A complete treatment cycle was defined as 28 days of once daily continuous treatment with ceritinib.
| Study group | Role | What they receive |
|---|---|---|
| Inflammatory myofibroblastic tumor (IMT) | Experimental | Patients diagnosed with IMT with a confirmed translocation involving the ALK gene Receives: Drug: Ceritinib (LDK378) |
| Anaplastic large cell lymphoma (ALCL) | Experimental | Patients with a diagnosis of ALCL histologically or cytologically confirmed to be ALK-positive Receives: Drug: Ceritinib (LDK378) |
| Glioblastoma (GBM) | Experimental | Patients with GBM with a translocation involving the ALK gene Receives: Drug: Ceritinib (LDK378) |
| Any other ALK-positive tumor | Experimental | Patients with any other ALK-positive tumor. Patients in this arm included adenocarcinoma (n= 2), sarcoma (1) and other (2). Receives: Drug: Ceritinib (LDK378) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease Control Rate (DCR) Based on Investigator Assessments for Participants With at Least 16 Weeks of Treatment
The DCR is defined as the percentage of patients with complete response (CR), partial response (PR) or stable disease (SD) at 16 weeks from the start of ceritinib treatment. The assessment criteria are: Solid Tumors (RECIST 1.1., Response Evaluation Criteria in Solid Tumors); GBM (RECIST 1.1 and RANO, Response Evaluation in Neuro-Oncology); Hematologic tumors (Cheson).
Measured: Baseline up to approximately 16 weeks
Secondary outcomes (5)
Overall Response Rate (ORR) Per Investigator Assessment
ORR is defined as the percentage of patients with best overall response of complete response (CR) or partial response (PR) based on local assessment according to RECIST 1.1, RANO or Cheson hematological criteria.
Measured: Baseline, every 8 weeks until disease progression or end of treatment, whichever came first assessed up to approximately 84 weeks
Duration of Response (DOR) Per Investigator Assessment
DOR is defined as the time from date of first documented CR or PR to date of first documented disease progression or death due to any cause
Measured: Baseline, every 8 weeks until disease progression or end of treatment, whichever came first, assessed up to approximately 84 weeks
Time to Response (TTR) Per Investigator Assessment
TTR is defined as the time from date of the first dose to date of first documented response (CR or PR)
Measured: Baseline, every 8 weeks until disease progression or end of treatment, whichever came first, assessed up to approximately 84 weeks
Progression Free Survival (PFS) Per Investigator Assessments
PFS is defined as the time from the date of first dose of ceritinib to the date of first documented disease progression or death from any cause
Measured: Baseline, every 8 weeks until disease progression or death from any cause, assessed for up to approximately 84 weeks
Percent of Participant Deaths During Treatment and Follow-up
Deaths due to any cause during treatment and 30 day follow-up
Measured: Baseline up to approximately 84 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2015 (estimated)
- Study start6 May 2016
- Primary completion20 Aug 2018
- Study completion20 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Tumors With Aberrations in ALKStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Depending on the tumor type, subjects were to be enrolled into one of the following parallel arms: ALCL (anaplastic large cell lymphoma); IMT (inflammatory myofibroblastic tumor); glioblastoma (GBM), and any other ALK+ tumor. If there were 5 or more subjects of the same tumor type in the "Any other ALK+ tumor" arm, then a separate arm was to be opened for that specific tumor type.
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02465528
- Sponsor's protocol ID
- CLDK378A2407
- Status last verified
- Dec 2019
- First submitted
- 29 May 2015
- Last updated
- 27 Dec 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Open Label, Multi-center, Multi-arm Study of Ceritinib in Patients With Advanced Solid Tumors and Hematological Malignancies Characterized by Genetic Abnormalities of Anaplastic Lymphoma Kinase (ALK)
- ClinicalTrials.gov ID
- NCT02465528
- Acronym / sponsor ID
- CLDK378A2407
- Conditions
- Tumors With Aberrations in ALK, Anaplastic Large Cell Lymphoma, Inflammatory Myofibroblastic Tumor, Glioblastoma
- Keywords
- ALK, GBM, hematological malignancy, anaplastic lymphoma kinase, glioblastoma, anaplastic large cell lymphoma, IMT, inflammatory myofibroblastic tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 6 May 2016 (actual)
- Primary completion
- 20 Aug 2018 (actual)
- Study completion
- 20 Aug 2018 (actual)
- First posted
- 8 Jun 2015 (estimated)
- Results
- Posted 21 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is Proof-of-Concept (POC) study to assess the preliminary antitumor activity and safety and tolerablity using ceritinib (LDK378) in the treatment of life threatening tumors that are characterized by ALK genetic alteration (and/or overexpression in some diseases).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Depending on the tumor type, subjects were to be enrolled into one of the following parallel arms: ALCL (anaplastic large cell lymphoma); IMT (inflammatory myofibroblastic tumor); glioblastoma (GBM), and any other ALK+ tumor. If there were 5 or more subjects of the same tumor type in the "Any other ALK+ tumor" arm, then a separate arm was to be opened for that specific tumor type.
| Arm | Type | Receives |
|---|---|---|
| Inflammatory myofibroblastic tumor (IMT) | Experimental | Drug: Ceritinib (LDK378)Patients diagnosed with IMT with a confirmed translocation involving the ALK gene |
| Anaplastic large cell lymphoma (ALCL) | Experimental | Drug: Ceritinib (LDK378)Patients with a diagnosis of ALCL histologically or cytologically confirmed to be ALK-positive |
| Glioblastoma (GBM) | Experimental | Drug: Ceritinib (LDK378)Patients with GBM with a translocation involving the ALK gene |
| Any other ALK-positive tumor | Experimental | Drug: Ceritinib (LDK378)Patients with any other ALK-positive tumor. Patients in this arm included adenocarcinoma (n= 2), sarcoma (1) and other (2). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patient has a histologically or cytologically confirmed diagnosis of ALK positive (ALK+) tumor other than Non-Small Cell Lung Cancer (NSCLC).
- Patient must provide an archival or fresh tumor tissue before the first dose of the study drug for ALK testing at a Novartis designated central laboratory.
- Patient has WHO Performance Status (PS) ≤ 2
- Patient must have received at least one line of prior systemic treatment for recurrent, locally advanced and/or metastatic disease, and may have discontinued for:
- Patient has at least one measurable lesion as defined by appropriate guidelines. A lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation.
Key exclusion criteria (8 listed)
- Patient has ALK+lung cancer
- Patient with symptomatic CNS metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms.
- Patient with acute or chronic GI disease that may significantly alter the absorption of ceritinib.
- Patient with a history of pancreatitis or history of increased amylase or lipase that was due to pancreatic disease.
- Patient has history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis.
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 |
|---|---|---|
| Ceritinib (LDK378)Ceritinib was to be administered orally once daily at a dose of 750 mg (5 capsules of 150 mg) on a continuous dosing schedule. A complete treatment cycle was defined as 28 days of once daily continuous treatment with ceritinib. | Drug | Anaplastic large cell lymphoma (ALCL), Any other ALK-positive tumor, Glioblastoma (GBM), Inflammatory myofibroblastic tumor (IMT) |
Primary outcome
Disease Control Rate (DCR) Based on Investigator Assessments for Participants With at Least 16 Weeks of Treatment
Time frame: Baseline up to approximately 16 weeks
The DCR is defined as the percentage of patients with complete response (CR), partial response (PR) or stable disease (SD) at 16 weeks from the start of ceritinib treatment. The assessment criteria are: Solid Tumors (RECIST 1.1., Response Evaluation Criteria in Solid Tumors); GBM (RECIST 1.1 and RANO, Response Evaluation in Neuro-Oncology); Hematologic tumors (Cheson).
5 secondary outcomes
Overall Response Rate (ORR) Per Investigator Assessment
Time frame: Baseline, every 8 weeks until disease progression or end of treatment, whichever came first assessed up to approximately 84 weeks
Duration of Response (DOR) Per Investigator Assessment
Time frame: Baseline, every 8 weeks until disease progression or end of treatment, whichever came first, assessed up to approximately 84 weeks
Time to Response (TTR) Per Investigator Assessment
Time frame: Baseline, every 8 weeks until disease progression or end of treatment, whichever came first, assessed up to approximately 84 weeks
Progression Free Survival (PFS) Per Investigator Assessments
Time frame: Baseline, every 8 weeks until disease progression or death from any cause, assessed for up to approximately 84 weeks
Percent of Participant Deaths During Treatment and Follow-up
Time frame: Baseline up to approximately 84 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
14 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ceritinib (LDK378) in people with Tumors With Aberrations in ALK and Anaplastic Large Cell Lymphoma, run by Novartis Pharmaceuticals at 14 sites in 8 countries.
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 10 inclusion and 8 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 27 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in France, South Korea, Spain, Thailand, Czechia and 3 more countries. 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?
Yes. Results are posted in the registry (first posted 21 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Disease Control Rate (DCR) Based on Investigator Assessments for Participants With at Least 16 Weeks of Treatment (time frame: Baseline up to approximately 16 weeks). 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 27 Dec 2019.