GlioblastomaEarly Phase 1NCT02605746
Preoperative Ceritinib (LDK378) in Glioblastoma Multiforme and CNS Metastasis
A Early Phase 1 study testing ceritinib 750mg in people with Glioblastoma and Brain Metastases, run by St. Joseph's Hospital and Medical Center, Phoenix at 1 site in United States.
Trial summary
This is two parallel studies to examine pharmacokinetic (PK), pharmacodynamic (PD), and pharmacogenetic (PG) endpoints following short-interval therapy (10-14) daily doses without dose reduction and interruption) with the ALK (anaplastic lymphoma kinase) small-molecule inhibitor, ceritinib. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Brain Metastases
- What is being tested?
- ceritinib 750mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Feb 2016to 12 Jul 2019
- Phase
- Early Phase 1
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- One prior resection of GBM or MRI evidence of solid tumor CNS metastasis
- All GBM and NSLC metastases must be ALK+
- Eastern Cooperative Oncology Group performance status ≤2
- Archival tumor tissue block available for research use
- Ability to understand written informed consent
- Recovery from toxicities related to prior anticancer therapies to ≤ grade 2 (CTCAE v 4.03). Exception: patients with any grade alopecia
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- The following lab criteria are met:
- Absolute neutrophil count ≥ 1.5 x 10(9th power)/L
- Hemoglobin ≥ 8 g/dL
- Platelets ≥ 75 x 10(9th power)/L
- Serum total bilirubin ≤ 1.5 x upper limit of normal(ULN), except for patients with Gilbert's syndrome who 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
- Creatinine clearance ≥ 30 mL/min
- Patient has following lab values or has lab values corrected with supplements to be within normal limits at screening:
- Potassium ≥ LLN
- Magnesium ≥ LLN
- Phosphorus ≥ LLN
- Total calcium (corrected for serum albumin) ≥ LLN
Who cannot join
- Co-morbid condition(s) that prevent safe surgical treatment
- Active infection or fever > 38.5°C
- Patients with known hypersensitivity to any excipients of ceritinib
- Prior therapy with ceritinib
- 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 (affecting activities of daily living or requiring therapeutic intervention)
- Clinically significant uncontrolled heart disease and/or recent cardiac event (within 6 months), such as:
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- history of documented congestive heart failure (New York Heart Association functional classification III-IV);
- uncontrolled hypertension defined by a Systolic Blood Pressure ≥ 160 mm Hg and/or Diastolic Blood Pressure ≥ 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 > 450 msec using Fridericia correction on the screening ECG
- Impaired GI function or GI disease that may alter absorption of ceritinib or inability to swallow up to five ceritinib capsules daily
- Ongoing GI adverse events > grade 2 (e.g. nausea, vomiting, or diarrhea) at the start of the study
- Receiving medications that meet 1 of the following criteria and cannot be discontinued at least 1 week prior to start of treatment with ceritinib 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
- Pregnant or nursing (lactating) women.
- Women of child-bearing potential, unless they are using highly effective methods of contraception during dosing and for 3 months after the last dose of study treatment.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 0/II Study of Ceritinib (LDK378) in Preoperative Glioblastoma Multiforme (GBM) and CNS Metastasis Patients Scheduled for Resection to Evaluate Central Nervous System (CNS) Penetration
This is two parallel studies to examine pharmacokinetic (PK), pharmacodynamic (PD), and pharmacogenetic (PG) endpoints following short-interval therapy (10-14) daily doses without dose reduction and interruption) with the ALK (anaplastic lymphoma kinase) small-molecule inhibitor, ceritinib.
The Phase 0 study will investigate:
Read more
- first recurrence GBM patients and
- patients with CNS metastases from solid tumors such as, but not limited to, NSCLC (non-small cell lung cancer) and melanoma.
The CNS (central nervous system) metastases Phase 0 is designed to identify PK effects (in addition to PD, and PG effects on ALK-positive NSCLC metastases), while the GBM Phase 0 is designed to identify PK, PD, and PG effects in all patients.
Read the detailed description
This study is being done to learn about a new drug, Ceritinib (LKD378). The results of the study may reveal how the drug works for cancer that spreads to the brain (metastases) and for a type of brain cancer called glioblastoma (GBM). Subjects are persons scheduled to have surgery to remove the tumor.This study would test how much of the new drug is present in the tumor, blood, and cerebrospinal fluid (CSF) after taking the drug orally for 10-14 days before surgery. It is only given to patients who are already scheduled to have surgery to remove a tumor that has returned. If the drug seems to be working for a subject's tumor, subject will have the option to continue to receive it as part of a continuation study looking at the drug effect on preventing the tumor from recurring. Small samples of blood, tumor tissue, and CSF will be taken. These samples will be sent to and analyzed at the Barbara Ann Karmanos Cancer Institute (KCI) and to the Translational Genomics Research Institute (TGen). Subject involvement will be for 10-14 days before surgery and for 30 days following surgery. Patients with ALK+ solid tumors will be provided the option of continuing therapy until tumor progression. ALK positivity will be assessed by approved FISH test (Abbott Molecular Inc) using Vysis break apart probes (defined as 15% or more positive tumor cells), the Ventana IHC (immunohistochemistry) test, and/or NGS (next generation sequencing).
- Conditions
- Glioblastoma, Brain Metastases
- Being tested
- ceritinib 750mg
- Medical subject headings
- Glioblastoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ceritinib 750mgDrug
| Study group | Role | What they receive |
|---|---|---|
| 2-4 hours | Experimental | All patients will be orally-administered 10-14 doses of ceritinib 750mg with the final dose occurring at one of three intervals before brain tumor resection. This arm has the last ceritinib dose 2-4 hours prior to craniotomy for tumor resection. Receives: Drug: ceritinib 750mg |
| 4-8 hours | Experimental | All patients will be orally-administered 10-14 doses of ceritinib 750mg with the final dose occurring at one of three intervals before brain tumor resection. This arm has the last ceritinib dose 4-8 hours prior to craniotomy for tumor resection. Receives: Drug: ceritinib 750mg |
| 22-26 hours | Experimental | All patients will be orally-administered 10-14 doses of ceritinib 750mg with the final dose occurring at one of three intervals before brain tumor resection. This arm has the last ceritinib dose 22-26 hours prior to craniotomy for tumor resection. Receives: Drug: ceritinib 750mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma Concentration
Plasma concentration of Ceritinib after 10-14 oral doses of 750 mg. Will be summarized using descriptive statistics.
Measured: at pre-dose on day 10-14(Day 0), 0.5, 1, 2, 4, 6, 8, and 24 hours following single dose of CERITINIB
Cerebrospinal Concentration
Cerebrospinal concentration of Ceritinib. Will be summarized using descriptive statistics.
Measured: collected intraoperatively at 2-4, 4-8, and 22-26 hours following single dose of CERITINIB relative to the final dose on day 10-14
Intratumoral Concentration
Intratumoral concentration of Ceritinib. Will be summarized using descriptive statistics.
Measured: collected intraoperatively at 2-4, 4-8, and 22-26 hours following single dose of CERITINIB relative to the final dose on day 10-14
Secondary outcomes (4)
Tumor Tissue
Tumor tissue quantification of total and phosphorylated forms of ALK, JAK/STAT5B, and Caspase-3. Will be summarized using descriptive statistics.
Measured: at baseline(archival) and up to 26 hours post dosing
Tumor Cells in M-Phase
Number of tumor cells in M-phase of cell cycle (PH3). Will be summarized using descriptive statistics.
Measured: at baseline and up to 26 hours post dose CERITINIB
Double Strand DNA
Presence of double-strand DNA damage (γH2AX). Will be summarized using descriptive statistics.
Measured: at baseline and up to 26 hours post dose CERITINIB
Tissue Concentration
Tissue concentration of CERITINIB compared to contrast enhancing GBM vs. surrounding nonenhancing FLAIR-hyperintense GBM. Will be summarized using descriptive statistics.
Measured: 2-4, 4-8, and 22-26 hours post dosing relative to the final Day 10 dose, as compared to the immediate pre-operative MRI scan
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2015 (estimated)
- Study start17 Feb 2016
- Primary completion29 Nov 2018
- Study completion12 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies 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
- Early Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Joseph's Hospital and Medical Center, Phoenix
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis, Wayne State University, Translational Genomics Research Institute
- Responsible party
- Principal investigator, Nader Sanai, St. Joseph's Hospital and Medical Center, Phoenix
- Investigators
- Nader Sanai, MD, Principal investigator, Barrow Brain and Spine, Phoenix AZ
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02605746
- Sponsor's protocol ID
- PHX15BN068
- Status last verified
- Dec 2020
- First submitted
- 8 Sep 2015
- Last updated
- 11 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 0/II Study of Ceritinib (LDK378) in Preoperative Glioblastoma Multiforme (GBM) and CNS Metastasis Patients Scheduled for Resection to Evaluate Central Nervous System (CNS) Penetration
- ClinicalTrials.gov ID
- NCT02605746
- Acronym / sponsor ID
- PHX15BN068
- Conditions
- Glioblastoma, Brain Metastases
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- St. Joseph's Hospital and Medical Center, PhoenixUniversity, hospital or other
- Collaborators
- Novartis, Wayne State University, Translational Genomics Research Institute
- Study start
- 17 Feb 2016 (actual)
- Primary completion
- 29 Nov 2018 (actual)
- Study completion
- 12 Jul 2019 (actual)
- First posted
- 16 Nov 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.
This is two parallel studies to examine pharmacokinetic (PK), pharmacodynamic (PD), and pharmacogenetic (PG) endpoints following short-interval therapy (10-14) daily doses without dose reduction and interruption) with the ALK (anaplastic lymphoma kinase) small-molecule inhibitor, ceritinib.
The Phase 0 study will investigate:
- first recurrence GBM patients and
- patients with CNS metastases from solid tumors such as, but not limited to, NSCLC (non-small cell lung cancer) and melanoma.
The CNS (central nervous system) metastases Phase 0 is designed to identify PK effects (in addition to PD, and PG effects on ALK-positive NSCLC metastases), while the GBM Phase 0 is designed to identify PK, PD, and PG effects in all patients.
Detailed description
This study is being done to learn about a new drug, Ceritinib (LKD378). The results of the study may reveal how the drug works for cancer that spreads to the brain (metastases) and for a type of brain cancer called glioblastoma (GBM). Subjects are persons scheduled to have surgery to remove the tumor.This study would test how much of the new drug is present in the tumor, blood, and cerebrospinal fluid (CSF) after taking the drug orally for 10-14 days before surgery. It is only given to patients who are already scheduled to have surgery to remove a tumor that has returned. If the drug seems to be working for a subject's tumor, subject will have the option to continue to receive it as part of a continuation study looking at the drug effect on preventing the tumor from recurring. Small samples of blood, tumor tissue, and CSF will be taken. These samples will be sent to and analyzed at the Barbara Ann Karmanos Cancer Institute (KCI) and to the Translational Genomics Research Institute (TGen). Subject involvement will be for 10-14 days before surgery and for 30 days following surgery. Patients with ALK+ solid tumors will be provided the option of continuing therapy until tumor progression. ALK positivity will be assessed by approved FISH test (Abbott Molecular Inc) using Vysis break apart probes (defined as 15% or more positive tumor cells), the Ventana IHC (immunohistochemistry) test, and/or NGS (next generation sequencing).
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 2-4 hours | Experimental | Drug: ceritinib 750mgAll patients will be orally-administered 10-14 doses of ceritinib 750mg with the final dose occurring at one of three intervals before brain tumor resection. This arm has the last ceritinib dose 2-4 hours prior to craniotomy for tumor resection. |
| 4-8 hours | Experimental | Drug: ceritinib 750mgAll patients will be orally-administered 10-14 doses of ceritinib 750mg with the final dose occurring at one of three intervals before brain tumor resection. This arm has the last ceritinib dose 4-8 hours prior to craniotomy for tumor resection. |
| 22-26 hours | Experimental | Drug: ceritinib 750mgAll patients will be orally-administered 10-14 doses of ceritinib 750mg with the final dose occurring at one of three intervals before brain tumor resection. This arm has the last ceritinib dose 22-26 hours prior to craniotomy for tumor resection. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- One prior resection of GBM or MRI evidence of solid tumor CNS metastasis
- All GBM and NSLC metastases must be ALK+
- Eastern Cooperative Oncology Group performance status ≤2
- Archival tumor tissue block available for research use
- Ability to understand written informed consent
Key exclusion criteria (21 listed)
- Co-morbid condition(s) that prevent safe surgical treatment
- Active infection or fever > 38.5°C
- Patients with known hypersensitivity to any excipients of ceritinib
- Prior therapy with ceritinib
- 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 (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 |
|---|---|---|
| ceritinib 750mg | Drug | 2-4 hours, 22-26 hours, 4-8 hours |
Primary outcome
Plasma Concentration
Time frame: at pre-dose on day 10-14(Day 0), 0.5, 1, 2, 4, 6, 8, and 24 hours following single dose of CERITINIB
Plasma concentration of Ceritinib after 10-14 oral doses of 750 mg. Will be summarized using descriptive statistics.
Cerebrospinal Concentration
Time frame: collected intraoperatively at 2-4, 4-8, and 22-26 hours following single dose of CERITINIB relative to the final dose on day 10-14
Cerebrospinal concentration of Ceritinib. Will be summarized using descriptive statistics.
Intratumoral Concentration
Time frame: collected intraoperatively at 2-4, 4-8, and 22-26 hours following single dose of CERITINIB relative to the final dose on day 10-14
Intratumoral concentration of Ceritinib. Will be summarized using descriptive statistics.
4 secondary outcomes
Tumor Tissue
Time frame: at baseline(archival) and up to 26 hours post dosing
Tumor Cells in M-Phase
Time frame: at baseline and up to 26 hours post dose CERITINIB
Double Strand DNA
Time frame: at baseline and up to 26 hours post dose CERITINIB
Tissue Concentration
Time frame: 2-4, 4-8, and 22-26 hours post dosing relative to the final Day 10 dose, as compared to the immediate pre-operative MRI scan
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2020.
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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.
Nader Sanai, MD principal investigator
Barrow Brain and Spine, Phoenix AZ
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing ceritinib 750mg in people with Glioblastoma and Brain Metastases, run by St. Joseph's Hospital and Medical Center, Phoenix at 1 site in United States.
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 18 inclusion and 21 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: finished, as of the sponsor's last update on 11 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Plasma Concentration (time frame: at pre-dose on day 10-14(Day 0), 0.5, 1, 2, 4, 6, 8, and 24 hours following single dose of CERITINIB). The study lists 3 primary outcomes in all. 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 11 Dec 2020.